Advertisement

Chemotherapy of the Leukaemias

  • John Kempton Harold Rees
Part of the European School of Oncology book series (ESO MONOGRAPHS)

Abstract

This review attempts to discuss the most recent developments in the treatment of the leukaemias, but in one chapter it cannot hope to be exhaustive. Some of the well established views and policies have been given less emphasis than the areas where debate remains, or where there have been interesting new ideas on the pathogenesis of the diseases and the therapeutic opportunities that these may provide. They are discussed in order: Myelodysplasic syndromes, acute myeloid leukaemia, acute lymphoblastic leukaemia, chronic myeloid leukaemia, chronic lymphatic leukaemia and hairy cell leukaemia. The section begins with a short history which may help to put our ideas today into perspective.

Keywords

Chronic Lymphocytic Leukaemia Myelodysplastic Syndrome Acute Promyelocytic Leukaemia Acute Myeloid Leukaemia Acute Lymphoblastic Leukaemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bennett JH: Case of hypertrophy of the spleen and liver in which death took place from suppuration of the blood. Edin Med Surg J 1845 (64):413–415Google Scholar
  2. 2.
    Craigie D: Case of disease of the spleen in which death took place in consequence of the presence of purulent matter in the blood. Edin Med Surg J 1945(64):400–401Google Scholar
  3. 3.
    Virchow R: Weisses Blut. N Notiz Geb Nat Heilk 1845(36):151–153Google Scholar
  4. 4.
    Barth J: Alteration du sang remarquable par la predominance des globules blancs ou muquex; hypertrophie considerable de la rate. Bull et Mem Soc Méd Hôp Paris 1856 (3):55–56Google Scholar
  5. 5.
    Donné A: Cours de Microscopie Complémentaire des Etudes Médicales, Anatomie Microscopique et Physiologique des Fluides de l’Economie. JB Baillière, Paris 1844 pp 132Google Scholar
  6. 6.
    Fuller HW: Particulars of a case in which enormous enlargement of the spleen and liver, together with dilataion of the blood vessels of the body were found coincident with a peculiarly altered condition of the blood. Lancet 1846 (ii):43–44Google Scholar
  7. 7.
    Bennett JH: Leucocythaemia, or White Cell Blood, in relation to the physiology and pathology of the lymphocytic glandular system. Sutherland & Cox, Edinburgh 1852Google Scholar
  8. 8.
    Virchow R: Die Leukaemie. In: Gesammelte Abhandlungen zur wissenschäftlichen Medizin. Meidinger Sohn & Comp, Frankfurt 1856 pp 190Google Scholar
  9. 9.
    Barthez F: Procès verbal de la séance du 9 janvier 1856 (Discussion on leukocythemia). Bull et Mem Soc Méd Hôp Paris 1856 (3):59–61Google Scholar
  10. 10.
    Neumann E: Ueber die bedeutung des Knochenmarkes für die Blutbildung. Centrabl Med Wiss 1868 (6):689–691Google Scholar
  11. 11.
    Neumann E: Ueber myelogene Leukaemie. Berliner Klin Wochenschr 1878 (15):69–71Google Scholar
  12. 12.
    Bizzozero G: Sulla funzione ematopoietica del midollo delle ossa R.C.R. 1st Lomb Sci Lett 1868 (2 ser 1):815–818Google Scholar
  13. 13.
    Bizzozero G: Su di un nuovo elemento morfologico del sangue dei mammiferi e delta sua importanza nella trombosi e nella coagulazione. Osservatore 1882 (17):785–787 (transi into German in Virchows Arch Path Anat 1882 (90):261–332Google Scholar
  14. 14.
    Tavassoli M, Yoffey JM: Bone Marrow Structure and Function. Alan R Liss Inc, New York 1983Google Scholar
  15. 15.
    Lissauer H: Zwei fälle von Leukämie. Berliner Klin Wochenschr 1865 (2):403–404Google Scholar
  16. 16.
    Forkner CE and Scott TFM: Arsenic as therapeutic agent in chronic myelogenous leukaemia: preliminary report. JAMA 1931 (97):3–5CrossRefGoogle Scholar
  17. 17.
    Gunz FW: Leukaemia in the past. In: Henderson E and Lister TA (eds) Leukaemia. WB Saunders & Co, Philadelphia 1990Google Scholar
  18. 18.
    Muratet L: Faure-Fremiet. Confidential report of the French Gas Service, 1918;Google Scholar
  19. 19.
    Zunz G: Report to the Interallied Gas Conference, Paris 1918Google Scholar
  20. 20.
    Stewart MJ: Report on cases of poisoning by “mustard gas” (dichlorethyl sulphide) with special reference to the histological changes and to the alterations on the leucocyte count. Report of the Chemical Warfare Committee, Great Britain, Med Res Com Rep No 17,1918Google Scholar
  21. 21.
    Krumbhaar EB: Role of the blood and the bone marrow in certain forms of gas poisoning. I. Peripheral blood changes and their significance. JAMA 1919 (72):39–41CrossRefGoogle Scholar
  22. 22.
    Pappenheimer AM and Vance M: The effects of intravenous injections of dichloroethyl sulphide in rabbits, with special reference to its leucotoxic action. J Exp Med 1920 (31):71–94PubMedCrossRefGoogle Scholar
  23. 23.
    Gilman A and Phillips FS: Biological actions and therapeutic applications of B-chloroethylamines and sulfides. Science 1946 (103):409–415CrossRefGoogle Scholar
  24. 24.
    Gilman A: Symposium on advances in pharmacology resulting from war research: therapeutic applications of chemical warfare. Fed Proc 1946 (5):285–292PubMedGoogle Scholar
  25. 25.
    Goodman LS, Wintrobe MM, Damashek W et al: Nitrogen mustard therapy: use of methyl-bis-(B-chloroethyl) amine hydrochloride and tris-(B-chloroethyl) amine hydrochloride for Hodgkin’s disease, lymphosarcoma, leukaemia and certain allied and miscellaneous disorders. JAMA 1946 (132):126–132CrossRefGoogle Scholar
  26. 26.
    Freireich EJ: Nitrogen mustard therapy (landmark perspective). JAMA 1984 (251):2262–2269PubMedCrossRefGoogle Scholar
  27. 27.
    Heilman FR and Kendall EC: The influence of 11 dehydro-17-hydroxycorticosterone (Compound E) on the growth of a malignant tumor in the mouse. Endocrinology 1944 (34):416–420CrossRefGoogle Scholar
  28. 28.
    Rhoads CP, Barker WH: Refractory Anaemia: analysis of 100 cases. JAMA 1938 (110):794–796CrossRefGoogle Scholar
  29. 29.
    Hamilton-Paterson JL: Preleukaemic anaemia. Act Haematol 1949 (2):309–316CrossRefGoogle Scholar
  30. 30.
    Rheingold JJ, Kaufman R, Adelson E, Lear A: Smouldering acute leukaemia. N Engl J Med 1963 (268):812–815PubMedCrossRefGoogle Scholar
  31. 31.
    Dameshek W, Gunz FW: Classification of leukemia. In: Leukemia. Grune & St ration, New York 1958 p16Google Scholar
  32. 32.
    Linman JW, Sarni Ml: The preleukemic syndrome. Semin Haematol 1974 (11):93–100Google Scholar
  33. 33.
    Greenberg PL, Mana B: The preleukemic syndrome. Am J Med 1979 (66):951–958PubMedCrossRefGoogle Scholar
  34. 34.
    Cohen JR, Gregen WP, Greenberg PL, Schrier SL: Subacute myeloid leukemia. Am J Med 1979 (66):959–966PubMedCrossRefGoogle Scholar
  35. 35.
    Bjorkman SD: Chronic refractory anaemia with sideroblastic bone marrow. A study of four cases. Blood 1956 (ii):250–259Google Scholar
  36. 36.
    Gruneberg H: The anaemia of flexed-tail mice (Mus musculus L) II siderocytes: J Genetics 1942 (44):246–272CrossRefGoogle Scholar
  37. 37.
    Dreyfus B, Rochant H, Sultan C et al: Les anemies refractaires avec exces de myeloblastes dans la moelle: Etude de onze observations. Nouv Presse Medecin 1970 (78):359–364Google Scholar
  38. 38.
    Linman JW: Myelomonocytic leukaemia and its preleukaemic phase. J Chronic Disease 1970 (22):49–60CrossRefGoogle Scholar
  39. 39.
    Bennett JM, Catovksy D, Daniel M-T et al: Proposals for the classification of the acute leukaemias. Br J Haematol 1976 (33):451–458PubMedCrossRefGoogle Scholar
  40. 40.
    Bennett JM, Catovsky D, Daniel M-T et al. Proposals for the classification of the myelodysplasic syndromes. Br J Haematol 1982 (51):189–199PubMedGoogle Scholar
  41. 41.
    Groupe Français de Morphologie Hématologique, French Registry of Acute Leukemia and Myelodysplasic Syndromes: Age distribution and hemograin analysis of the 4,496 cases recorded during 1982–1983 and classified according to FAB criteria. Cancer 1987 (60):1385–1394CrossRefGoogle Scholar
  42. 42.
    Todd WM, Pierre RV: Preleukaemia: a long term prospective study of 326 patients. Scand J Haematol 1986 (36):114–120CrossRefGoogle Scholar
  43. 43.
    Coiffier B, Adeleine P and Viala JJ: Dysmyelopoietic syndromes: a search for prognostic factors in 193 patients. Cancer 1983 (52):83–90PubMedCrossRefGoogle Scholar
  44. 44.
    Foucar K, Langdon II RM and Armitage JO et al: Myelodysplastic syndromes: a clinical and pathological analysis of 109 cases. Cancer 1985 (56):553–561PubMedCrossRefGoogle Scholar
  45. 45.
    Vallespi T, Torrabadella M, Julia A et al: Myelodysplastic syndromes: a study of 101 cases according to the FAB classification. Br J Haematol 1985(61):83–92PubMedCrossRefGoogle Scholar
  46. 46.
    Oscier DG: Myelodysplastic Syndromes. Bailliere’s Clin Haematol 1987 (1):389–425CrossRefGoogle Scholar
  47. 47.
    Cartwright RA, Alexander FE, McKinney PA et al: Leukaemia and lymphoma: an atlas of distribution within areas of England and Wales. Leukaemia Research Fund, London 1990 pp 32–40Google Scholar
  48. 48.
    Stott H, Fox W, Girling DJ et al: Acute leukaemia after busulphan. Br Med J 1977 (ii):1513–1517CrossRefGoogle Scholar
  49. 49.
    Buckman R, Cuzick J, Galton DAG: Long term survival in myelomatosis: a report to the MRC Working Party on Leukaemia in Adults. Br J Haemat 1982 (52):589–599CrossRefGoogle Scholar
  50. 50.
    Cuzick J, Erskine S, Edelman D, Galton DAG: A comparison of the incidence of the myelodysplastic syndrome and acute myeloid Leukaemia following melphalan and cyclophosphamide treatment. Br J Cancer 1987 (55):523–529PubMedCrossRefGoogle Scholar
  51. 51.
    Bloomfield CD: Chromosome abnormalities in secondary myelodysplastic syndromes. Scand J Haematol 1986 (36 Suppl 45):82–90CrossRefGoogle Scholar
  52. 52.
    Prchal JT, Trockmorton DW, Carroll AJ et al: A common progenitor for myeloid and lymphoid cells. Nature 1978 (274):590–591PubMedCrossRefGoogle Scholar
  53. 53.
    Raskind WH, Tirumali N, Tacobson R, et al: Evidence for a multistep pathogenesis of a myelodysplastic syndrome. Blood 1984 (63):1318–1323PubMedGoogle Scholar
  54. 54.
    Abkowitz JL, Ott RM, Holly RD and Adamson JW: Clonal evolution following chemotherapy induced stem cell depletion in cats heterozous for glucose-6-phosphate dehydrogenase. Blood 1988 (71):1687–1692PubMedGoogle Scholar
  55. 55.
    Hirai H, Kobayashi Y, Mano H et al: A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome. Nature 1987 (327):430–432PubMedCrossRefGoogle Scholar
  56. 56.
    Bos JL, Toksoz D, Marshall CJ et al: Amino acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia. Nature 1985 (315):726PubMedCrossRefGoogle Scholar
  57. 57.
    Needlemann SW, Kraus MH, Scrivastava SK et al: High frequency of N-ras activation in acute myelogenous leukaemia. Blood 1986 (67):753–757Google Scholar
  58. 58.
    Bos JL, Verlan-de Vries M, Vander Eb AJ et al: Mutations in N-ras predominate in acute myeloid leukemia. Blood 1987(69):1237–1241PubMedGoogle Scholar
  59. 59.
    Lyons J, Janssen JWG, Bartram C et al: Mutations of Ki-ras and N-ras oncogenes in myelodysplastic syndromes. Blood 1988 (71):1707–1712PubMedGoogle Scholar
  60. 60.
    Forrester K, Almoguera C, Han K et al: Detection of high incidence of K-ras oncogene during human colon tumourigenesis. Nature 1987 (327):298–303PubMedCrossRefGoogle Scholar
  61. 61.
    Robenhuis S, van de Wetering ML, Mooi WJ et al: Mutational activation of the K-ras oncogene: A possible pathogenetic factor in adenocarcinoma of the lung. N Engl J Med 1987 (317):929–935CrossRefGoogle Scholar
  62. 62.
    Albino AP, Le Strange R and Olirff AT: Transforming ras genes from human melanoma: A manifestation of tumour heterogeneity? Nature 1984 (308):69–72PubMedCrossRefGoogle Scholar
  63. 63.
    Barbacid M: Mutagens, oncogenes and cancer. Trends Genet 1986 (2):188CrossRefGoogle Scholar
  64. 64.
    Padua RA, Carter G, Hughes D et al: RAS mutations in myelodysplastic detected by amplification, oligonucleotide hybridization and transformation. Leukemia 1988 (2):503–510PubMedGoogle Scholar
  65. 65.
    Shen WP, Aldrich TH, Venta-Perez G: Expression of normal and mutant ras proteins in human acute leukemia. Oncogene 1987 (1):157–165PubMedGoogle Scholar
  66. 66.
    Klein G, Klein E: Evolution of tumours and the impact of molecular oncology. Nature 1985 (315):190–195PubMedCrossRefGoogle Scholar
  67. 67.
    Ridge SA, Worwood M, Oscier D et al: FMS mutations in myelodysplastic, leukemic and normal subjects. Proc Natl Acad Sci 1990 (87):1377–1380PubMedCrossRefGoogle Scholar
  68. 68.
    Russell NH and Reilly IAG: Role of autocrine growth factors in the leukemic transformation of the myelo-dysplastic syndromes. Leukemia 1989 (3):83–84PubMedGoogle Scholar
  69. 69.
    Pierre RV, Catovsky D, Mufti GJ et al: Clinical-cytogenetic correlations in myelodysplastic (preleukemia). In: Report of the 6th International Workshop on Chromosomes in Leukemia. London 1987. Cancer Genet Cytogenet 1989 (40):149–161PubMedCrossRefGoogle Scholar
  70. 70.
    Second International Workshop on Chromosomes in Leukaemia 1979: Chromosomes in preleukemia. Cancer Genet Cytogenet 1980 (2):108–113CrossRefGoogle Scholar
  71. 71.
    Third MIC Cooperative Study Group: Recommendations for a morphologic, immunologic and cytogenetic (MIC) working classification of the primary and therapy-related myelodysplastic syndromes. Cancer Genet Cytogenet 1988 (32):1CrossRefGoogle Scholar
  72. 72.
    Knapp RH, Dewald GW, Pierre RV: Cytogenetic studies in 174 consecutive patients with pre leukemic or myelodysplastic syndromes. Mayo Clin Proc 1985 (60):507–516PubMedGoogle Scholar
  73. 73.
    Van den Berghe H: The 5q- syndrome. Scand J Haematol 1986 (36):78–81CrossRefGoogle Scholar
  74. 74.
    Pedersen-Bjergaard J, Vindelov V, Phillip P et al: Varying involvement of peripheral granulocytes in the clonal abnormality 7 in bone marrow cells in preleukemia secondary to treatment of other malignant tumours: cytogenetic results compared with results of flow cytometric DNA analysis and neutrophil Chemotaxis. Blood 1982 (60) 172–179PubMedGoogle Scholar
  75. 75.
    Scheres JMJC, Hustinx TWJ, Geraedts JPM et al: Translocation 1 ;7 in hematologic disorders: a brief review of 22 cases. Cancer Genet Cytogenet 1985 (18):207–213PubMedCrossRefGoogle Scholar
  76. 76.
    Nowell PC: Cytogenetics of preleukemia. Cancer Cytogenet 1982 (5):265–278CrossRefGoogle Scholar
  77. 77.
    Yunis JJ, Rydell RE, Oken MM et al: Refined chromosome analysis as an independent prognostic indicator in de novo myelodysplastic syndromes. Blood 1986 (67):1721–1727PubMedGoogle Scholar
  78. 78.
    Bloomfield CD, Garson OM, Volin L et al: t(1;3)(p36;q21) in acute non lymphocytic leukaemia: a new clinicopathological association. Blood 1986 (68):320–322 (letter)Google Scholar
  79. 79.
    de la Chapelle A, Knuutila W and Elonen E: Translocation (2;11)(p21;q23) in acute non lymphocytic leukaemia: a non-random assocation. Scand J Haematol 1986 (36 Suppl 45):91–97CrossRefGoogle Scholar
  80. 80.
    Le Beau MM, Westbrook CA, Diaz Mo et al: Evidence for the involvement of GM-CSF and FMS in the deletion (5q) in myeloid disorders. Science 1986(231)984–987PubMedCrossRefGoogle Scholar
  81. 81.
    Nienhuis AW, Bunn HF, Turner PH et al: Expression of the human cfms proto oncogene in hemopoietic cells and its deletion in the 5q-syndrome. Cell 1985 (42):421–428PubMedCrossRefGoogle Scholar
  82. 82.
    Tricot G, De Wolf -Peeters C, Vlietinck R, Verwilghen RL: Bone marrow histology in myelodysplastic syndromes II. Prognostic value of abnormal localisation of immature precursors in MDS. Br J Haematol 1984 (58):217–225PubMedCrossRefGoogle Scholar
  83. 83.
    Frisch B, Bartl R: Bone marrow histology in myelodysplastic syndromes. Scand J Haematol 1986 (36 Suppl 45):21–37CrossRefGoogle Scholar
  84. 84.
    Mufti GJ, Steven JR, Oscier DG et al: Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 1985 (590):425–433CrossRefGoogle Scholar
  85. 85.
    Tricot G, Vlietinck R, Verwilghen RL: Prognostic factors in the myelodysplastic syndromes: A Review. Scand J Haematol 1986 (36 Suppl 45):107–113CrossRefGoogle Scholar
  86. 86.
    Koeffler HP: Myelodysplastic syndromes (Preleukemia). Sem Haematol 1986 (23):284–299Google Scholar
  87. 87.
    Weisdorf DJ, Oken MM, Johnson GJ, Rydell RE: Chronic myelodysplastic syndrome: short survival with or without evolution to acute leukemia. Br J Haematol 1983 (55):691–700PubMedCrossRefGoogle Scholar
  88. 88.
    Worsley A, Oscier DG, Stevens J et al: Prognostic features of chronic myelomonocytic leukaemia: a modified Bournemouth score gives the best prediction of survival. Br J Haematol 1988 (68):17–21PubMedCrossRefGoogle Scholar
  89. 89.
    Solal-Celigny P, Desaint B, Herrera A et al: Chronic myelomonocytic leukaemia according to FAB classification :analysis of 35 cases. Blood 1984 (63):634–638PubMedGoogle Scholar
  90. 90.
    Allessandrino EP, Orlandi E, Brusamolino E et al: Chronic myelomonocytic leukaemia:clinical features, cytogenetics and prognosis in 30 consecutive cases. Haematol Oncol 1985 (3):147–155CrossRefGoogle Scholar
  91. 91.
    Fenaux P, Jouet JP, Zandecki M et al: Chronic and subacute myelomonocytic leukaemia in the adult: a report of 60 cases with special reference to prognostic factors. Br J Haematol 1987 (65):101–106PubMedCrossRefGoogle Scholar
  92. 92.
    Ruutu T, Partenen S, Lintula R et al: Erythroid and granulocyte — macrophage colony function in myelodysplastic syndromes. Scand J Haematol 1984(32):395–402PubMedCrossRefGoogle Scholar
  93. 93.
    Zittoun R: Subacute and chronic myelomonocytic leukaemia: a distinct haematological entity. Br J Haematol 1976 (32):1–7PubMedCrossRefGoogle Scholar
  94. 94.
    Varela BL, Chuang C, Woll JE: Modifications in the classification of primary myelodysplastic syndromes. The addition of a scoring system. Haematol Oncol 1985 (3):55–63CrossRefGoogle Scholar
  95. 95.
    Kerhofs H, Hermans J, Haak HL and Leeksma CHW: Utility of the FAB classification for myelodysplastic syndromes, investigation of prognostic features in 256 cases. Br J Haematol 1987 (65):73–81CrossRefGoogle Scholar
  96. 96.
    Major P, Egan EM, Beardsley G et al: Lethality of human myeloblastic correlates with the incorporation of Ara-C into DNA. Proc Nat Acad Sci 1981 (78):3235–3238PubMedCrossRefGoogle Scholar
  97. 97.
    Griffin JD, Munroe D, Major P, Kufe D: Induction of differentiation of human myeloid leukemic cells by inhibitors of DNA synthesis. Exper Haematol 1982 (10):744–781Google Scholar
  98. 98.
    Weinstein HJ, Griffin JW, Feeney J et al: Pharmacokinetics of continuous intravenous and subcutaneous infusions of cytosine arabinoside. Blood 1982 (59):1351–1353PubMedGoogle Scholar
  99. 99.
    Spriggs D, Sokal J, Griffin J, Kufe D: Low dose Ara-C administration by continuous subcutaneous infusion: a pharmacologic evaluation. Cancer Drug Delivery 1986 (3):211–216PubMedCrossRefGoogle Scholar
  100. 100.
    Griffin JD, Spriggs D, Wisch JS et al: Treatment of preleukemic syndromes with continuous intravenous infusion of low dose cytosine arabinoside. J Clin Oncol 1985 (3):982–991PubMedGoogle Scholar
  101. 101.
    Castaigne S, Daniel MT, Tilly H et al: Does treatment with Ara-C in low dosage cause differentiation of leukemic cells? Blood 1983 (62):85–86PubMedGoogle Scholar
  102. 102.
    Ishikuna H, Sawada H, Okazaki T et al: The effect of low dose ara-c in acute nonlymphoblastic leukemias and atypical leukemia. Br J Haematol 1984(58):9–18CrossRefGoogle Scholar
  103. 103.
    Tricot G, De Bock R, Dekker AW et al: Low dose cytosine arabinoside (ara-C) in myelodysplastic syndromes. Br J Haematol 1984 (58):231–240PubMedCrossRefGoogle Scholar
  104. 104.
    Winter JN, Variakojis D, Gaynor ER et al: Low dose cytosine arabinoside (ara-C) therapy in the myelodysplastic syndromes and acute leukemia. Cancer 1985 (56):443–449PubMedCrossRefGoogle Scholar
  105. 105.
    Roberts JD, Ershler WB, Tindle BH, Stewart JA: Low dose cytosine arabinoside in the myelodysplastic syndromes and acute myelogenous leukemia. Cancer 1985 (56):1001–1005PubMedCrossRefGoogle Scholar
  106. 106.
    Degos L, Castaigne S, Tilly H et al: Treatment of leukemia with low dose ara-C: a study of 160 cases. Semin Oncol 1985 (12 Suppl 3):196–199PubMedGoogle Scholar
  107. 107.
    Bolwell BJ, Cassileth PA, Gale RP: Low dose cytosine arabinoside in myelodysplastic and acute myelogenous leukemia: A review. Leukemia 1987 (1):575–579PubMedGoogle Scholar
  108. 108.
    Lishner M, Curbis JE, Minkin S, McCulloch EA: Interaction between retinoic acid and cytosine arabinoside affecting the blast cells of acute myeloblastc leukaemia. Leukemia 1989 (3):784–788.PubMedGoogle Scholar
  109. 109.
    Castaigne S, Chomienne C, Ballerine P et al: Alltrans retinoic acid: A novel differentiation therapy for acute promyelo-cytic leukaemia. Blood 1989 (74 Suppl 1):434 (abstract)Google Scholar
  110. 110.
    Gallagher RE, Said F, Pua I et al: Expression of retinoic acid receptor. mRNA in human leukaemia cells with variable responsiveness to retinoic acid. Leukemia 1989 (3):789–795PubMedGoogle Scholar
  111. 111.
    Elias L, Hoffman R, Boswell S and Bonnern E: A trial of recombinant alpha-2 interferon in the myelodysplastic syndrome. Blood 1985 (66 Suppl):675 (abstract)Google Scholar
  112. 112.
    Herberman RB, Holden HT: Natural killer cells as antitumour effector cells. JNCI 1979 (62):441–445PubMedGoogle Scholar
  113. 113.
    Djeu JY, Heinbaugh JA, Holden HT, Herberman RB: Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol 1979(122):175–181PubMedGoogle Scholar
  114. 114.
    Haliotis T, Roder J, Klein M et al: Chediak-Higashi gene in humans. J Exper Med 1980 (151):1039–1048CrossRefGoogle Scholar
  115. 115.
    Tayaki S, Kitagawa S, Takeda A et al: Natural killer-interferon system in patients with preleukemic states. Br J Haematol 1984 (58):71–81CrossRefGoogle Scholar
  116. 116.
    Sorskaar D, Forre O, Albrechtsen D et al: Decreased natural killer cell activity versus normal killer cell markers in mononuclear cells from patients with smouldering leukaemia. Scand J Haematol 1986 (37):154–161PubMedCrossRefGoogle Scholar
  117. 117.
    Kerndup G, Mayer K, Ellegard J et al: Natural killer (NK) activity and antibody dependent cellular cytotoxicity (ADCC) in primary preleukaemic syndrome. Leuk Res 1984 (8):239–247CrossRefGoogle Scholar
  118. 118.
    Pedersen-Bjengaard J, Haahr S, Philip P et al: Abolished production of interferon by leucocytes of patients with the aquired cytogenetic abnormalities 5q-or -5 in seconday and de novo acute non-lymphocytic leukaemia. Br J Haematol 1980(46):211–223CrossRefGoogle Scholar
  119. 119.
    Goldstein D, Laszlo J: Interferon therapy in Cancer from imaginon to interferon. Cancer Res 1986 (46):4315–4329PubMedGoogle Scholar
  120. 120.
    Taylor-Papadimitriou J, Rozengurt E: Interferons as regulators of cell growth and differentiation. In: Taylor-Papadimitriou J (ed) Interferons: Their Impact in Biology and Medicine. Oxford University Press, Oxford 1985 pp 81–98Google Scholar
  121. 121.
    Elias L, Van Epps DE, Smith KJ et al: A trial of recombinant alpha2 interferon in the myelodysplastic syndrome:2 characterisation and response of granulocyte and platelet dysfunction. Leukemia 1987 (1):111–115PubMedGoogle Scholar
  122. 122.
    Galvani DW, Cawley JC, Nethersall A, Bottomley JM: Alpha interferon in myelodysplastic. Br J Haematol 1987(66):145–146PubMedGoogle Scholar
  123. 123.
    Elias L, Hoffman R, Boswell S et al: A trial of recombinant alpha interferon in the myelodysplastic syndromes. 1:Clinical results. Leukemia 1987 (1):105–110PubMedGoogle Scholar
  124. 124.
    Gisslinger H, Chott A, Linkesch W: Long-term interferon therapy in myelodysplastic syndromes. Leukemia 1990 (4):91–94Google Scholar
  125. 125.
    Vadhan-Raj S, Keating M, Le Maistre A et al: Effects of recombinant human granulocyte-macrophage colony stimulating factor in patients with myelodysplastic syndromes. N Engl J Med 1987(317):1545–1552PubMedCrossRefGoogle Scholar
  126. 126.
    Ganser A, Volkers B, Greher J et al: Recombinant human granulocyte macrophage colony-stimulating factor in patients with myelodysplastic syndromes — A phase l/ll trial. Blood 1989 (73):31–37PubMedGoogle Scholar
  127. 128.
    Groopman JE, Mitsuyasu RT, De Leo MJ et al: Effect of recombinant human granulocyte-macrophage stimulating factor on myelopoiesis in the acquired immune deficiency syndrome. N Engl J Med 1987(317):593–598PubMedCrossRefGoogle Scholar
  128. 129.
    Antin JH, Smith BR, Holmes W and Rosenthal DS: Phase l/ll study of recombinant human granulocyte-macrophage colony stimulating factor in aplastic anaemia and myelodysplastic syndrome. Blood 1988 (72):705–713PubMedGoogle Scholar
  129. 130.
    Negrin RS, Haenber DH, Nagler A et al: Treatment of myelodysplastic syndromes with recombinant human granulocytic colony-stimulating factor: a phase l/ll trial. Ann Intern Med 1989 (110):976–984PubMedGoogle Scholar
  130. 131.
    Groopman JE, Molina JM and Scadden DT: Hemopoietic growth factors: Biology and clinical applications. N Engl J Med 1989 (321):1449–1459PubMedCrossRefGoogle Scholar
  131. 132.
    Koeffler HP, Hirji K, Itra L et al: 1,25 Dihyroxyvitamin D3; in vivo and vitro effects on human preleukaemic cells. Cancer Treat Rep 1985 (69):1399–1407PubMedGoogle Scholar
  132. 133.
    Oscier DG, Worsley A, Hamblin TJ, Mufti GJ: Treatment of chronic myelomonocytic leukaemia with low dose etoposide. Br J Haematol 1989 (72):468–471PubMedCrossRefGoogle Scholar
  133. 134.
    Johnson E, Parapia LA: Successful oral chemotherapy with Idarubicin in Refractory Anaemia. Eur J Haematol 1987 (39): 278–281PubMedCrossRefGoogle Scholar
  134. 135.
    De Witte T, Zwaan F, Gratwohl A et al: Allogeneic bone marrow transplantation in secondary leukaemias and myelodysplastic syndromes. Bone Marrow Transpl 1988 (3 Suppl 1):142–143Google Scholar
  135. 136.
    Appelbaum FR, Storb R, Rainberg RE: Treatment of preleukemic syndromes with marrow transplantation. Blood 1987 (69):92–96PubMedGoogle Scholar
  136. 137.
    Bessis M: Blood Smears Reinterpreted. Springer Verlag, Berlin/Heidelberg 1977CrossRefGoogle Scholar
  137. 138.
    Bennett JM, Catovsky D, Daniel M-T et al: Prepared revised criteria for the classification of acute myeloid leukaemia: a report of the French-American-British Cooperative GroupAm J Med 1985 (103):620–629Google Scholar
  138. 139.
    Hayhoe FGJ: A modern classification of the acute non-lymphoblastic leukaemias. Bone Marrow Transplant 1989 (4 Suppl 1):70–72PubMedGoogle Scholar
  139. 140.
    Hayhoe FGJ: Classification of the acute leukaemias. Blood Reviews 1988 (2):186–193PubMedCrossRefGoogle Scholar
  140. 141.
    Report of the MIC Cooperative Study Group: Morphologic, immunologic and cytogenetic (MIC) working classification of the acute myeloid leukaemias. Br J Haematol 1988 (68):487–494CrossRefGoogle Scholar
  141. 142.
    Selvin S, Levin LI, Merrill DW, Winkelstein W Jr: Selected epidemiologic observations of cell-specific leukaemia mortality in the United States 1969–1977. Am J Epidemiol 1983 (117):140–152PubMedGoogle Scholar
  142. 143.
    Gilliam AG: Age, sex and race selection at death from leukaemia and the lymphomas. Bbod 1953 (8):693–702Google Scholar
  143. 144.
    Freireich EJ: Methods for evaluating response to treatment on adult acute leukaemia. Blood Cells 1983(9):5–20PubMedGoogle Scholar
  144. 145.
    Amaki I, Hattoni K, Bennett JM et al: FAB classification of acute leukaemias correlates with response to chemotherapy. Acta Haematol Jpn 1984(47):206–238Google Scholar
  145. 146.
    Preisler HD: Prediction of response to chemotherapy in acute myelocytic leukaemia. Blood 1980 (56):361–367PubMedGoogle Scholar
  146. 147.
    Curtis JE, Messner HA, Hasselback R et al: Contributions of host and disease-related attributes to the outcome of patients with acute myelogenous leukaemia. J Clin Oncol 1984 (2):253–259PubMedGoogle Scholar
  147. 148.
    Yunis JJ and Brunning RD: Prognostic significance of chromosomal abnormalities in acute leukaemia and myelodysplastic syndromes. Clin Haematol 1986 [15]:597–620PubMedGoogle Scholar
  148. 149.
    Grier HE, Gelber RO, Camilta BM et al: Prognostic factors in childhood acute myelogenous leukaemia. J Clin Oncol 1987 (5):1026–1030PubMedGoogle Scholar
  149. 150.
    Ritter J, Crentzig V, Schellong G: Improved treatment results in the myelocytic subtypes FAB M1-M4 but not in FAB M5 after intensification of induction therapy: results of the German childhood AML studies BFM-78 and BFM-83. Haematol Bbod Transf 1990(33):185–192Google Scholar
  150. 151.
    Amadori S, Mandelli A, Ceci A et al: Results of the Italian AIEOP/LAM 8204 study for the treatment of childhood AML: an update. Bone Marrow Transpl 1989(4):114–115Google Scholar
  151. 152.
    Chessels JM, O’Callaghan U and Hardisty RM: Acute myeloid leukaemia in childhood: clinical factors and prognosis. Br J Haematol 1986 (63):555–564CrossRefGoogle Scholar
  152. 153.
    Stuber CP, Cuthbert SJ, Ravindranath Y et al: Therapy of childhood acute non lymphocytic leukaemia: the Pediatric Oncology Group Experience (1977–1988). Haematol Blood Transf 1990(33):188–209Google Scholar
  153. 154.
    Kalwinski D, Mirro J Jr, Schell M et al: Early intensification of chemotherapy for childhood acute nonlymphoblastic leukaemia: improved remission induction with a fine drug regimen including etoposide. J Clin Oncol 1988 (6):1134–1143Google Scholar
  154. 155.
    Yates J, Glidewell O and Wiernik P: Cytosine arabinoside with Daunorubicin or Adriamycin for therapy of Acute Myelocytic Leukaemia: A CALGB Study. Blood 1982 (60): 454–462PubMedGoogle Scholar
  155. 156.
    Vogler WR, Winton EF, Gordon DS et al: A randomised comparison of post remission therapy in acute myelogenous leukaemia: a Southeastern Cancer Study Group Trial. Blood 1984 (63):1039–1045PubMedGoogle Scholar
  156. 157.
    Rees JKH and Gray R: Remission induction and post remission therapy in acute myelogenous leukaemia: British MRC Study. Haematol Blood Transf 1990 (33):243–248Google Scholar
  157. 158.
    Petti MC, Broccia G, Carona F et al: Therapy of acute myelogenous leukaemia in adults. Haematol Blood Transf 1990 (33):240–253Google Scholar
  158. 159.
    Kurrle E, Ehninger E, Fackler-Schwalbe E et al: Consolidation therapy with high dose cytosine arabinoside: Experience of a prospective study in Acute Myeloid Leukaemia. Haematol Blood Transf 1990(33):254–260Google Scholar
  159. 160.
    Buchner T, Hiddemann W and Blasuis S: Adult AML: The role of chemotherapy intensity and duration. Two studies of the AML Cooperative Group. Haematol Blood Transf 1990 (33):261–266Google Scholar
  160. 161.
    Cassileth PA, Harrington DP and Hines JD: Comparison of post remission therapies in adult acute myeloid leukaemia: preliminary analysis of an ECOG study. Haematol Blood Transf 1990 (33):267–270Google Scholar
  161. 162.
    Hayat M, Zittoun R and Strychmans P: EORTC Leukaemia Group Trials in Acute Myeloid Leukaemia. Haematol Blood Transf 1990 (33):271–276Google Scholar
  162. 163.
    Labar B, Nemet D, Minigo H et al: Aclarubicin in the treatment of de-novo acute myelocytic leukaemia. New Trends in the Treatment of Acute Leukaemia, Dubrovnik 1989Google Scholar
  163. 164.
    Jehn U, Zittoun R, Suciu S et al: Randomised comparison of intensive maintenance treatment for adult acute myelogenous leukaemia using either cyclic alternating drugs or repeated courses of the induction-type chemotherapy: AML6 Trial of the EORTC Cooperative Group. Haematol Blood Transf 1990(33):277–289Google Scholar
  164. 165.
    Amadori S, Ceci A and Connelli A: Therapy of childhood acute myelogenous leukaemia. An update of the AIEOP/LAM 8204 study. Blood Transf 1990 (33):222–225Google Scholar
  165. 166.
    Grier HE, Gelber RE and Claver LA: Intensive sequential chemotherapy for children with acute myelogenous leukaemia. Haematol Blood Transf 1990 (33):193–197Google Scholar
  166. 167.
    Steuber CP, Culbert SJ, Ravindranath Y et al: Therapy of childhood acute nonlymphocytic leukaemia. The Pediatric Oncology Group Experience (1977–1988). Haematol Blood Transf 1990(33):198–209Google Scholar
  167. 168.
    Lampkin BC, Woods WG, Buckley JD et al: Preliminary results of intensive therapy of children and adults with acute non lymphocytic leukaemia. A Childrens’ Cancer Study Group report. Haematol Blood Transf 1990 (33):210–214Google Scholar
  168. 169.
    Ritter J, Creutzig U and Schellong G: Improved treatment results in the myelocytic subtypes FAB M1-4 but not in FAB M5 after intensification of induction therapy: Results of the German Childhood AML Studies BFM-78 and BFM-83. Haematol Blood Transf 1990 (33):185–192Google Scholar
  169. 170.
    The Toronto Leukaemia Study Group: Results of chemotherapy for unselected patients with acute myeloblastc leukaemia: effect of exclusion or interpretation of results. Lancet 1986 (i):786–788Google Scholar
  170. 171.
    Copplestone JA, Smith AG, Oscier DG and Hamblin T: True outlook in acute myeloblastic leukaemia. Lancet 1986 (i): 1104 (letter)CrossRefGoogle Scholar
  171. 172.
    Preisler HD: Failure of remission induction in acute myelogenous leukaemia. Med Pediatr Oncol 1978 (4):275–276PubMedCrossRefGoogle Scholar
  172. 173.
    Estey EH, Keating MJ, McCredie KB et al: Causes of initial remission induction failure in acute myelogenous leukaemia. Blood 1982 (60): 309PubMedGoogle Scholar
  173. 174.
    Rees JKH, Gray R, Hayhoe FGJ: The Ninth British Medical Research Council Trial for the Treatment of Acute Myeloid Leukaemia. Haematol Blood Trans 1987(30):35–37Google Scholar
  174. 175.
    Bodey GP, Buckley M, Sathe YS et al: Quantitative relationships between circulating leukocytes and infection in patients with acute leukaemia. Ann Int Med 1986 (64):328–240Google Scholar
  175. 176.
    Gaya H: Antimicrobial therapy in neutropenic patients with malignant disease. In: Klastersky J (ed) Clinical Use of Combinations of Antibiotics. Hodden & Staughton, London 1975 pp 117–125Google Scholar
  176. 177.
    Rubin M, Hathorn JW and Pizzo PA: Controversies in the management of febrile neutropenic cancer patients. Cancer Invest 1986 (6): 167–184CrossRefGoogle Scholar
  177. 178.
    Rubin M, Walsh T, Butler K et al: The febrile neutropenic patient: newer options for emperical therapy. Haematol Blood Transf 1990 (33):531–538Google Scholar
  178. 179.
    Walsh TJ and Pizzo PA: Noxcomial fungal infections. Ann Rev Microbiol 1988 (42):517–545CrossRefGoogle Scholar
  179. 180.
    Gold JW: Opportunistic fungal infections in patients with neoplastic disease. Am J Med 1984 (76):458–463PubMedCrossRefGoogle Scholar
  180. 181.
    Meunier F and Klastersky J: Recent development in prophylaxis and therapy of invasive fungal infections in granulocytopenic cancer patients. Eur J Cancer and Clin Oncol 1988 (24):539–544CrossRefGoogle Scholar
  181. 182.
    Crumbacker II CS: Molecular targets of antiviral therapy. N Engl J Med 1989 (321):163–172CrossRefGoogle Scholar
  182. 183.
    Hughes WT, Rivena GK, Sohell MJ et al: Successful intermittent chemoprophylaxis for Pneumocystis carinii pneumonitis. N Engl J Med 1987(316):1627–1632PubMedCrossRefGoogle Scholar
  183. 184.
    Schimpff SC, Young VM, Green WH et al: Origin of infection in acute non-lymphocytic leukaemia: significance of hospital acquisition of potential pathogens. Ann Intern Med 1972 (77):707–714PubMedGoogle Scholar
  184. 185.
    Young LS: Double a-lactam therapy in the immunocomprised host. J Automicrob Chemo 1985 (16):4–6CrossRefGoogle Scholar
  185. 186.
    Infections in haematology. In: Prentice HG (ed) Clinics in Haematology. WB Saunders & Co, London, Philadelphia, Toronto 1984Google Scholar
  186. 187.
    Brandt SJ, Peters WP, Atwater SK et al: Effect of recombinant human granulocyte-macrophage colony stimulating factor or haemopoietic reconstitution after high dose chemotherapy and autologous bone marrow transplantation. N Engl J Med 1988 (318):869–876PubMedCrossRefGoogle Scholar
  187. 188.
    Gabrilone JL, Jakubowski A, Scher H et al: Effect of granulocyte stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urathelium. N Engl J Med 1988 (318):1414–1422CrossRefGoogle Scholar
  188. 189.
    Antman KS, Griffin JD and Elias A: Effect of recombinant human granulocyte-macrophage colony stimulating factor or chemotherapy induced myelosuppression. N Engl J Med 1988 (319):594–598Google Scholar
  189. 190.
    Buchner T, Hiddemann W, Koenigsman M et al: Recombinant human granulocyte colony-stimulating factor after therapy for acute leukaemias at higher age or after relapse. Haematol Blood Transf 1990 (33):724–731Google Scholar
  190. 191.
    Hermann F, Schulz G, Wieser M et al: Effect of granulocyte-macrophage stimulating factor on neutropenia and related morbidity induced by myelotoxic chemotherapy. Haematol Blood Transf 1990(33):717–723Google Scholar
  191. 192.
    Andreef M, Tafuni A, Hegewisch-Becker S: Colony-Stimulating factors (rhG-CSF, rhGM-CSF, rh1L-3 and BCFG) recruit myeloblastic and lymphblastic leukemic cells and enhance the cytotoxic effects of cytosine arabinoside. Haematol Blood Transf 1990(33):747–762Google Scholar
  192. 193.
    Vellenga E, Young DC, Wagner K et al: The effects of GM-CSF and G-CSF in promoting growth of clonagenic cells in acute myeloblastic leukemia. Blood 1987 (69):1771–1776PubMedGoogle Scholar
  193. 194.
    Schipperus MR, Vink N, Lindemans J et al: In vitro growth kinetics of myeloid progenitor cells of myelodysplastic patients in response to granulocyte macrophage colony stimulating factor and Interleukin 3. Haematol Blood Transf 1990 (33):98–102Google Scholar
  194. 195.
    Schrader C, Reuter M, Mempel K et al: In vitro effects of G-CSF, GM-CSF and 1L-3an Leukemic cells of children with acute non lymphoblastic leukemia. Haematol Blood Transf 1990 (33):95–97Google Scholar
  195. 196.
    Estey EH, Kantaryian HM, Beran M et al: Treatment of poor prognosis newly diagnosed acute myelagenous leukemia with high dose Cytosine Arabinoside (Ara-C) and rHUGM-CSF. Haematol Blood Transf 1990 (33):732Google Scholar
  196. 197.
    Brittingham TE, Chaplin H: Febrile transfusion reactions caused by sensitivity to donor leukocytes and platelets. JAMA 1975 (165):819–825CrossRefGoogle Scholar
  197. 198.
    Brubaker DB: Immunologically mediated immediate adverse effects of blood transfusions. Plasma Ther Transf Technol 1985 (6):19–30Google Scholar
  198. 199.
    Class FHJ, Smeenk RJT, Schmidt R et al: Alloimmunisation against the MLC antigens after platelet transfusion is due to contaminating leukocytes in the platelet suspension. Exp Haematol 1981 (90):84–89Google Scholar
  199. 200.
    Lang DJ, Ebent PA: Reduction of post perfusion cytomegalovirus infections following the use of leukocyte depleted blood: a comparison of filtration techniques. Transfusion 1977 (17):391–395PubMedCrossRefGoogle Scholar
  200. 201.
    Mijovic V, Brozovic B, Hughes ASB, Davies TD: Leukocyte depleted blood: a comparison of filtration techniques. Transfusion 1983 (23):30–32PubMedCrossRefGoogle Scholar
  201. 202.
    Cassileth PA, Begg CB, Silber R: Prolonged unmaintained remission after intensive consolidation therapy in adult acute nonlymphocytic leukemia. Cancer Treat Rep 1987 (71):137–140PubMedGoogle Scholar
  202. 203.
    Preisler HD, Raza A, Early A: Intensive remission consolidation therapy in the treatment of acute nonlymphocytic leukemia. J Clin Oncol 1987 (5):722–730PubMedGoogle Scholar
  203. 204.
    Tricot G, Boogaents MA, Vlietinck R: The role of intensive remission induction and consolidation therapy in patients with acute myeloid leukaemia. Bri J Haematol 1987 (66):37–44CrossRefGoogle Scholar
  204. 205.
    Champlin R, How Winston D et al: Treatment of adults with acute myelogenous leukemia: Prospective evaluation of high dose cytarabine in consolidation chemotherapy and with bone marrow transplantation. Semin Oncol 1987 (14 Suppl1):1–6PubMedGoogle Scholar
  205. 206.
    Wal SN, Herzig RH, Phillips GL: High dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: An update. Semin Oncol 1987 (14 Suppl):12–17Google Scholar
  206. 207.
    Eastey E, Keating MJ, Plunkett W: Continuous infusion high-dose cytosine arabinoside without antraycyclines as induction andintensification therapy in adults under age 50 with newly diagnosed acute myclogenous leukemia. Semin Oncol 1987 (14 Suppl):58–63Google Scholar
  207. 208.
    Capizzi RL, Pole M, Cooper MR et al: Treatment of poor risk acute leukemia with sequential high dose Ara-C and asparaginase. Blood 1984 (63): 694–700PubMedGoogle Scholar
  208. 209.
    Kurrle E, Ehninge G, Fackler-Schwalbe E et al: Consolidation therapy with high-dose cytosine Arabinoside: Experiences of a prospective study in acute myeloid leukemia. Haematol Blood Transf 1990(33):254–260Google Scholar
  209. 210.
    Zittoun R, Marie JP, Zittoun J et al: Modulation of Cytosine Arabinoside (Ara-C) and high dose Ara-C in acute leukemia. Semin Oncol 1985 (12):139–143PubMedGoogle Scholar
  210. 211.
    Plunkett W, Heinemann V, Estey E, Keating MJ: Pharmacologically directed design of Leukemia Therapy. Haematol Blood Transf 1990 (33):610–613Google Scholar
  211. 212.
    Plunkett W, Liliemark JO, Estey E, Keating MJ: Saturation of Ara-CTP accumulation during high dose Ara-C therapy: Pharmacologic rationale for intermediate dose Ara-C. Semin Oncol 1987 (14):159–166PubMedGoogle Scholar
  212. 213.
    Karp JE, Donehower RC, Dole GB and Burke PJ: Correlation of drug-perturbed marrow cell growth kinetics and intracellular 1-B-D-arabinofuranosylcytosine metabolism with clinical response in adult acute myelogenous leukaemia. Blood 1987 (69): 4,1134–1140PubMedGoogle Scholar
  213. 214.
    Bernard J, Lasnanet J, Chome J et al: A cytologicai and histological study of acute promyelocytic leukaemia. J Clin Path 1963 (16):319–325PubMedCrossRefGoogle Scholar
  214. 215.
    Bennett, J., Catovsky D., Daniel, M-T et al: A variant form of hypergranular promyelocytic leukaemia (M3). Ann Int Med 1980 (92):261 (letter)PubMedGoogle Scholar
  215. 216.
    Rosenthal RL: Acute promyelocytic leukaemia associated with hypofibrinogenemia. Blood 1963 (21):495–500PubMedGoogle Scholar
  216. 217.
    Didsheim P, Thrombold JS, Vandervoot RLE et al: Acute promyelocytic leukaemia with fibrinogen and factor V deficiencies. Blood 1964 (23):717–728Google Scholar
  217. 218.
    Gralnick HR and Sultan C: Acute promyelocytic leukaemia, haemorrhagic manifestations and morphologic criteria. Br J Haematol 1975 (29): 373– 376 (Annotation)PubMedCrossRefGoogle Scholar
  218. 219.
    Gonault-Heilmann M, Chardon E, Sultan C et al: The procoagulant factor of leukaemic promyelocytes: Demonstration of immunologic cross reactivity with human brain tissue factor. Br J Haematol 1975 (30):151–158CrossRefGoogle Scholar
  219. 220.
    Sultan C, Gonault-Heilmann M and Tulliez M: Relationship between blast cell morphology and occurrence of a syndrome of disseminated intravascular coagulation. Br J Haematol 1973 (24):255–259PubMedCrossRefGoogle Scholar
  220. 221.
    Bernard J, Weil-Boiron M et al: Acute promyelocytic leukaemia: results of treatment by daunorubicin. Blood 1973 (41):489–496PubMedGoogle Scholar
  221. 222.
    Marty M, Ganem G, Fischer J et al: Leucémie aigue promyelocytaire: étude rétrospective de 119 malades traités par Daunorubicine. Nouv Rev Fr Hematol 1984 (26):371–378PubMedGoogle Scholar
  222. 223.
    Cordonnier C, Vernaut JP, Brun B et al: Acute promyelocytic leukaemia in 57 primarily untreated patients. Cancer 1985 (55):18–25PubMedCrossRefGoogle Scholar
  223. 224.
    Collins AJ, Bloomfield CD, Peterson BA et al: Acute promyelocytic leukaemia: management of the coagulopathy during Daunorubicin-prednisone remission induction. Arch Int Med 1978 (138):1677–1680CrossRefGoogle Scholar
  224. 225.
    Goldberg MA, Ginsberg D, Mayer RJ et al: Is heparin administration necessary during induction chemotherapy for patients with acute promyelocytic leukemia? Blood 1987 (69):187–191PubMedGoogle Scholar
  225. 226.
    Venook AP, Shuman MA and Corash L: Prophylactic heparin in APL. Blood 1987 (70):886–887PubMedGoogle Scholar
  226. 227.
    Hoyle CF, Swirsky DM, Freedman L and Hayhoe FGJ: Beneficial effects of heparin in the management of patients with APL. Br J Haematol 1988(68):283–298PubMedCrossRefGoogle Scholar
  227. 228.
    Avvisati G, Buller HR, Wouter ten Cate J and Mandelli F.: Transexamic acid for control of haemorrhage in promyelocytic leukaemia. Lancet 1989 (ii):122–124CrossRefGoogle Scholar
  228. 229.
    Ogston D (ed) Antifibrinolytic Drugs. Chemistry, Pharmacology and Clinical Usage. John Wiley, Chicester 1984 pp 81–83Google Scholar
  229. 230.
    Sandler RM, Liebman HA, Patch MJ et al: Antithrombin III and anti activated factor X activity in patients with acute promyelocytic leukaemia and intravascular coagulation treatment with heparin. Cancer 1983 (51):681–685PubMedCrossRefGoogle Scholar
  230. 231.
    Chabner BA: The oncologic end game: Karnofsky memorial lecture. J Clin Oncol 1986 (4):625–638Google Scholar
  231. 232.
    Kartner N and Ling V: Multidrug resistance in cancer. Sci Am 1989 (iii):26–33Google Scholar
  232. 233.
    Piller GJ: Leukaemia Research Fund International Research Symposium on cytotoxic drug resistance in leukaemia and other malignancies. Leukaemia 1989(3):461–467Google Scholar
  233. 234.
    Pastan I and Gottesman M: Multidrug resistance in human cancer. N Engl J Med 1987 (316):1388–1393PubMedCrossRefGoogle Scholar
  234. 235.
    Juranka PF, Zastawny Rl and Ling V: P-glycoprotein: multidrug resistance and a superfamily of membrane-associated transport proteins. FASEB 1989 (3):2583–2592Google Scholar
  235. 236.
    Ma DDF, Schurr RD, Davey RA et al: Detection of a multidrug resistant phenotype in acute non lymphoblastic leukaemia. Lancet 1987 (i):135–137CrossRefGoogle Scholar
  236. 237.
    Kartner N, Evernden-Porelle D, Bradley G and Ling V: Detection of P-glycoprotein in multidrug resistant cell lines by monoclonal antibodies. Nature 1985 (316):820–823PubMedCrossRefGoogle Scholar
  237. 238.
    Bell DR, Trent JM, Willard HF et al: Chromosomal location of human P-glycoprotein gene sequences. Cancer Genet Cytogenet 1987 (25):141–148PubMedCrossRefGoogle Scholar
  238. 239.
    Wilson CM, Serrano AE and Wasley A: Amplification of a gene related to mammalian MDR genes in drug-resistant Plasmodium falciparum. Science 1989 (244):1184–1186PubMedCrossRefGoogle Scholar
  239. 240.
    McGrath JP and Varshavsky A: The yeast STE 6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein. Nature 1989 (340):400–404PubMedCrossRefGoogle Scholar
  240. 241.
    Tsuruo T, Lida H, Tsukagoshi S, Sakurai Y et al: Overcoming of vincristine resistance in P388 leukaemia in vivo and in vitro enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 1981 (41):1967–1972PubMedGoogle Scholar
  241. 242.
    Maruyama Y, Murohashi I and Nava N: Effects of verapamil on the cellular accumulation of daunorubicin in blast cells and on the chemosensitivity of leukaemic blast progenitors in acute myelogenous leukaemia. Br J Haematol 1989 (72):357–362PubMedCrossRefGoogle Scholar
  242. 243.
    Twentyman PR, Fox NE and White DJG: Cyclosporin A and its analogues as modifiers of adriamycin and vincristine resistance in multidrug resistant human lung cancer cell line. Br J Cancer 1987(56):55–57PubMedCrossRefGoogle Scholar
  243. 244.
    Twentyman PR: Resistance modification by non-immunosuppressive cyclosporins. Br J Cancer 1988(57):254–258PubMedCrossRefGoogle Scholar
  244. 245.
    Twentyman PR, Fox NE and Rees JKH: Chemosensitivity testing of fresh leukaemic cells using the MTT colorimetric assay. Br J Haematol 1989(71):19–24PubMedCrossRefGoogle Scholar
  245. 246.
    Arrick BA and Nathan CF: Glutathione metabolism as a detriment of therapeutic efficacy: a review. Cancer Res 1984 (44):4224–4232PubMedGoogle Scholar
  246. 247.
    Russo A, Carmichael J, Friedman N et al: The roles of intracellular glutathione in antineoplastic chemotherapy. Int J Radiat Oncol Biol Phys 1986 (12):1347–1354PubMedCrossRefGoogle Scholar
  247. 248.
    Tew KD, Schisselbauer JC, Clapper ML and Kuzmich S: Glutathione S-transferases and resistance to alkylating agents. Hayes JD, Pickett CB, Mantle TJ (eds) Proc 3rd Int GST Conf, Edinburgh 1989 pp 309–318Google Scholar
  248. 249.
    Tew KD, Bomber AM and Hoffman SF: Ethacrynic acid and Piriton as enhancers of cytotoxicity in drug-resistant and sensitive cell lines. Cancer Res 1988(48):3617–3625Google Scholar
  249. 250.
    Clapper ML, Dwyer PJ and Tew KD: Sensitisation of tumours to alkylating agents using inhibitors of glutathione S-transferases. Hayes JD, Pickett CB, Mantle TJ (eds) Proc 3rd Int GST Conf, Edinburgh 1989 pp 451–459Google Scholar
  250. 251.
    McVie JG: DNA topoisomerases in cancer treatment. Br Med J 1988 (296):1145–1146CrossRefGoogle Scholar
  251. 252.
    Potsmeil M, Hsiang YH and Liu LF: DNA topoisomerase 11 as a potential factor in drug resistance of human malignancies. NCI Monographs 1987 (4):105–109Google Scholar
  252. 253.
    M, Ikebuchi K, Leary AG: Humoral regulation of stem cell proliferation. Ann NY Acad Sci 1989 (554):185–191PubMedCrossRefGoogle Scholar
  253. 254.
    M, Yoffey JM: Bone marrow structure and function. Alan Liss Inc, New York 1983Google Scholar
  254. 255.
    Francis GE, Pinsky CP: Growth and differentiation control. In: Pinedo HM, Chabner BA and Longo DL (eds) Cancer Chemotherapy and Biological Response Modifiers. Elsevier, Amsterdam 1988 pp 507–544Google Scholar
  255. 256.
    Bagby GC Jr: Interleukin-1 and haematopoiesis. Blood Rev 1989 (3):152–161PubMedCrossRefGoogle Scholar
  256. 257.
    Broxmeyer HE, Moore HAS: Communication between white cells and the abnormalities of this in Leukaemia. Biochem. Biophys Acta. 1978 (516) 129–166PubMedGoogle Scholar
  257. 258.
    Fliender TM, Steinbach KH: Repopulating potential of haemopoietic precursor cells. Blood Cells 1988 (14):393–410Google Scholar
  258. 259.
    K, Nakeff A: Lymphoid cell regulation of haematopoiesis. Int J Cell Cloning 1989 (7):2–12PubMedCrossRefGoogle Scholar
  259. 260.
    McCulloch EA: Stem cells in normal and leukaemic haemopoiesis. Blood 1983 (62):1–13PubMedGoogle Scholar
  260. 261.
    McCulloch EA, Minden MD, Miyanchi J et al: Stem cell renewal and differentiation in acute myeloblastic leukaemia. J Cell Sci 1988 (10):267–281Google Scholar
  261. 262.
    Sieff CA: Haematopoietic growth factors. JNCI 1987(79):1549–1557Google Scholar
  262. 263.
    Bagby GC Jr: Production of multilineage growth factors by haemopoitic stromal cells: an intercellular regulatory network involving mononuclear phagocytes and interleukin-1. Blood Cells 1987 (13):147–159PubMedGoogle Scholar
  263. 264.
    Wright EG, Lord BI: Production of stem cell proliferation regulators by fractionated haemopoietic stem cell suspensions. Leuk Res 1979(3):15–22PubMedCrossRefGoogle Scholar
  264. 265.
    Bl, Lu LF, Pojda Z, Spooncer E: Inhibitor of haemotapoietic CFU-S proliferation: assay production, sources and regulatory mechanisms. In: A Najman A, Guigon M, Gorin NC, Mary JY (eds) The Inhibitors of Haematopoiesis. John Libbey Eurotext 1987 (162):227–240Google Scholar
  265. 266.
    F, Fache MP, Dumenil D, et al: Further studies of the biological activity of the CFU-S inhibitor peptide ACSDKP. Leukemia Res 1989 (13 Suppl 1):15–19Google Scholar
  266. 267.
    Greaves MY, Dowding CR, Riley GP, Greaves MF: Characterisation of stroma-dependent blast colony-forming cells in human marrow. J Cell Physiol 1987 (130):150–156PubMedCrossRefGoogle Scholar
  267. 268.
    R, Gallagher J, Spooner E: Heparan sulphate-bound growth factors: a mechanism for stromal cell mediated haemopoiesis. Nature 1988 (332):376–378PubMedCrossRefGoogle Scholar
  268. 269.
    Gordon MY, Riley GP, Clarke D: Heparan sulphate is necessary for adhesive interactions between human early haemopoietic progenitor cells and the extracellular matrix of the marrow microenvironment. Leukaemia 1988 (2):804–809Google Scholar
  269. 270.
    M, Najman A: The inhibitors of haematopoiesis. Int J Cell Cloning 1988 (6):69–75CrossRefGoogle Scholar
  270. 271.
    Broxmeyer HE, Bagnacki J, Ralph P et al: Monocyte-macrophage-derived acidic isoferritins: normal feedback regulators of granulocyte-monophage progenitor cells in vitro. Blood 1982 (60):595–607PubMedGoogle Scholar
  271. 272.
    Broxmeyer HE, Williams DE, Lu L et al: Biomolecules associated with suppression of myelopoiesis in normal conditions and during myeloid leukaemia and other related disorders In: Najman A, Guigon M, Gorin NC, Mary JY (eds) The Inhibitors of Haematopoiesis. John Libbey Eurotext 1987(162):139–148Google Scholar
  272. 273.
    Gentile PS, Peius LM: In vivo modulation of myelopoiesis by prostaglandin E2. II. Inhibition of CFU-GM cycle rate. Exper Haematol 1987 (15):119–123Google Scholar
  273. 274.
    M, Louden R, Kobayashi M, Trinchieri G: Gamma — interferon and lymphotoxin, released by activated T cells, synergise to inhibit granulocyte/macrophage colony formation T Exp Med 1986 (164):263–268CrossRefGoogle Scholar
  274. 275.
    R, Salem M, Pellens C, Dorssers L et al: Growth regulation of human acute myeloid leukaemia: effect of five recombinant haemopoietic factors in a serum-free culture system. Blood 1988 (72):1944–1949PubMedGoogle Scholar
  275. 276.
    Wu MC, Zaun MR, Wu FM: Inhibition of myeloid differentiation by inhibitors of ADP-ribosylation. FEBS Letters 1989 (244):338–342PubMedCrossRefGoogle Scholar
  276. 277.
    Broxmeyer HE, Williams DE: The production of myeloid blood cells and their regulation during health and disease. CRC Critical Reviews in Oncol/Haematol 1988 (4):173–226CrossRefGoogle Scholar
  277. 278.
    Metcalf D: The Haemopoietic Colony Stimulating Factors. Elsevier, Amsterdam 1984Google Scholar
  278. 279.
    Steinberg HN: Suppression of normal haemopoiesis in Leukaemia: in vivo and in vitro studies. In: Najman A, Guigon M, Gorin NC, Mary JY (eds) The Inhibitors of Haematopoiesis. John Libbey Eurotext 1987 (162):163–175Google Scholar
  279. 280.
    Steinberg HN, Tsiftsoglou AS, Robinson SH: Loss of suppression of normal bone marrow colony formation by leukaemia cell lines after differentiation is induced by chemical agents. Blood 1985 (65):100–106PubMedGoogle Scholar
  280. 281.
    Dorner MH, Broxmeyer HE, Silverstone A, Andreeff M: Biosynthesis of ferritin subunits from different cell lines of HL-60 human promyelocytic leukaemia cells and the release of acidic isoferritin: inhibitory activity against normal granulocytic-macrophage progenitor cells. Br J Haematol 1983 (55):47–52PubMedCrossRefGoogle Scholar
  281. 282.
    Petrides PE, Dittman K: Leukaemic cells HL-60 release a polypeptide which disturbs the interaction of various target cells with their extracellular matrix. Exper Haematol 1989 (17):534Google Scholar
  282. 283.
    R, Taheri MR, Katz F, Hoffbrand AV: The effect of the leukaemic cell line HL-60 and acute myeloblastic leukaemic cells before and after induction of differentiation on normal pluripotent haemotopoietic progenitors (CFU-GEMM). Leukaemia Res 1985 (9):441–448CrossRefGoogle Scholar
  283. 284.
    Stevens VL, Owens NE, Winter EF et al: Modulation of retinoic acid-induced differentiation of human leukemia (HL- 60) cells by serum factors and sphinganine. Cancer Res 1990 (50):222–226PubMedGoogle Scholar
  284. 285.
    Sartorelli AC: Malignant cell differentiation as a potential therapeutic approach. Br J Cancer 1985 (52):293–302PubMedCrossRefGoogle Scholar
  285. 286.
    Hassan HT and Rees JKH: Triple combination of retinoic acid + low concentration of cytosine arabinoside + hexamethylene bisacetamide induces differentiation of human AML blasts in primary culture. Haematol Oncol 1989 (7):429–440CrossRefGoogle Scholar
  286. 287.
    D: Vitamin A and retinoid in health and disease. N Engl J Med 1984 (310):1023–1031PubMedCrossRefGoogle Scholar
  287. 288.
    M, Roberts A: The role of retinoids in differentiation and carcinogenesis. Cancer Res 1983(43):3034–3040PubMedGoogle Scholar
  288. 289.
    Hoffman SJ, Robinson WA: Use of differentiation-inducing agents in myelodysplastic syndromes and acute lymphocytic leukaemia. Am J Haematol 1988 (28):124–127CrossRefGoogle Scholar
  289. 290.
    Mufti GJ, Oscier DG, Hamblin TJ, Bell AJ: Low dose cytarabine in the treatment of myelodysplastic syndromes and acute myeloid leukaemia. N Engl J Med 1983 (309):1653–1654PubMedCrossRefGoogle Scholar
  290. 291.
    Flynn PJ, Miller WJ, Weisdorf DJ et al: Retinoic acid treatment of acute promyelocytic leukaemia: in vitro and in vivo observations. Blood 1983 (62):1211–1217PubMedGoogle Scholar
  291. 292.
    B: Probable in vivo induction of differentiation by retinoic acid of promylocytes in acute promylocytic leukaemia. Br J Haematol 1984 (57):365–371PubMedCrossRefGoogle Scholar
  292. 293.
    L, Shroot B, deThé H et al: Retinoic acid in hematopoietic differentiation. Nouv Rev Fr Hématol 1990(32):25–38Google Scholar
  293. 294.
    C, Ballerini P, Huang M et al: In vitro effects of retinoic acid. Nouv Rev Fr Hématol 1990 (32):32–34PubMedGoogle Scholar
  294. 295.
    V, Ong ES, Segui P, Evans RM: Indentification of a receptor for the morphogen retinoic acid. Nature 1987 (330):624–629PubMedCrossRefGoogle Scholar
  295. 296.
    N, Petkovich M, Krust A et al: Identification of a second human retinoic acid receptor. Nature 1988(332):850–853PubMedCrossRefGoogle Scholar
  296. 297.
    A, Krust A, Petkovich M et al: Cloning of alpha and beta retinoic acid receptors and a novel receptor predominantly expressed in the skin. Nature 1989 (339):714–717PubMedCrossRefGoogle Scholar
  297. 298.
    Ragsdale CW Jr, Petkovich M, Gates PB: Identification of a novel retinoic acid receptor in regenerative tissues of the newt. Nature 1989 (341):654–657PubMedCrossRefGoogle Scholar
  298. 299.
    H, Yu-Chen Y, Shusong C et al: Use of All-Trans retinoic acid in the treatment of acute promyelocytic leukaemia. Blood 1988 (72):567–572Google Scholar
  299. 300.
    S, Chomienne C, Ballerini P et al: Alltrans retinoic acid: a novel differentiation therapy for acute promyelocytic leukaemia. Blood 1989 (74 Suppl 1)abstr 434Google Scholar
  300. 301.
    C, Ballerini P, Balitrand N et al: Retinoic acid therapy for promyelocytic leukaemia. Lancet 1989(ii):746–747CrossRefGoogle Scholar
  301. 302.
    Castaigne S, Chomienne C, Daniel M-T et al: Retinoic acids in the treatment of acute promyelocytic leukaemia. Nouv Rev Fr Hématol 1990(32):36–38PubMedGoogle Scholar
  302. 303.
    Hassan HT, Rees J: Triple combination of retinoic acid + 6 Thioguanine + hexamethylene bisacetamide induces differentiation of human AML blasts in primary culture. Leuk Res 1990 (14):109–117CrossRefGoogle Scholar
  303. 304.
    H, Okazaki T, Mochizuki T: Effects of antimetabolites and thymidine blockage on the induction of differentiation of HL-60 cells by retinoic acid or 1,25 — dihydroxy-vitamin D3. Exper Haematol 1985 (13):981–988Google Scholar
  304. 305.
    Y, Gavison R, Rachmilewitz EA, Fibach E: Expression of granulocytic functions by leukaemic promyelocytic HL-60 cells: differential induction by dimethyl sulphaxide and retinoic acid. Cell Differentiation 1987 (21):261–269PubMedCrossRefGoogle Scholar
  305. 306.
    H, Breitman TR: Combinations of recombinant human interferons and retinoic acid synergistically induce differentiation of the human promyelocytic leukaemia cell line HL-60. Blood 1987(69):501–507PubMedGoogle Scholar
  306. 307.
    Francis GE, Mufti GJ, Knowles SM et al: Differentiation induction in myelodysplastic and acute myeloid leukaemia: use of synergistic drug combinations. Leuk Res 1987 (11):971–977PubMedCrossRefGoogle Scholar
  307. 308.
    Lie SO and Slordahl SH: High-dose cytosine arabinoside and retinol in the treatment of acute myelogenous leukemia in childhood. Haematol and Blood Transf 1987 (30):399–402Google Scholar
  308. 309.
    Zuckerman SH, Surprenant YM, Tang J: Synergistic effect of GM-CSF and Vitamin D-3 on the differentiation of the human monocytic cell line U937. Blood 1988 (71):619–624PubMedGoogle Scholar
  309. 310.
    Kelsey SM, Newland AC, Makin HLJ: Vitamin D and Human Leukaemia. Br J Haematol 1989 (71):173–176PubMedCrossRefGoogle Scholar
  310. 311.
    Dawson DM, Rosenthal DS, Moloney WC: Neurological complications of acute leukemia in adults: Changing rate. Ann Int Med 1979 (79):541–544Google Scholar
  311. 312.
    Law IP, Blom J: Adult acute leukaemia: Frequency of central nervous system acute leukemia in adults. Cancer 1981 (47):184–196CrossRefGoogle Scholar
  312. 313.
    Steward DJ, Keating MJ, McCredie KB et al: Natural history of central nervous system acute leukemia in adults. Cancer 1981 (47):184–196CrossRefGoogle Scholar
  313. 314.
    Bennett JM, Cassileth P, Begg C: Central nervous system involvement in the acute myeloid leukemias (AML): the Eastern Cooperative Oncology Group (ECOG) experience. Blood 1984 (64):144aGoogle Scholar
  314. 315.
    Rees JKH, Gray R, Swirsky D, Hayhoe FGJ: Principal results of the Medical Research Council’s 8th acute myeloid leukaemia trial. Lancet 1986 (ii):1236–1241CrossRefGoogle Scholar
  315. 316.
    Weinstein HJ, Mayer RJ, Rosenthal DS et al: Treatment of acute myelogenous leukemia in children and adults. N Engl J Med 1980 (303):473–478PubMedCrossRefGoogle Scholar
  316. 317.
    Holmes R, Keating MJ, Cork A et al: A unique pattern of central nervous system leukemia in acute myelomonocytic leukemia associated with INV(16)(P13q22). Blood 1985 (65):1071–1078PubMedGoogle Scholar
  317. 318.
    Sakurai M, Kaneko Y, Abe R: Further characterisation of acute myelogenous leukaemia with t(8;21) chromosome translocation. Cancer Genet Cytogenet 1982 (6):143–152CrossRefGoogle Scholar
  318. 319.
    Andrew W: The Anatomy of Aging in Man and Animals. Grune & Stratton, New York 1971Google Scholar
  319. 320.
    Goldstein S, Harley CB, Moerman EJ: Some aspects of cellular aging. J Chron Dis 1983 (36):103–116PubMedCrossRefGoogle Scholar
  320. 321.
    Richey DP, Bender AD: Pharmacokinetic consequences of aging. Ann Rev Pharmacol Toxicol 1977 (17):49–65CrossRefGoogle Scholar
  321. 322.
    Editorial: Pharmacokinetics in the elderly Lancet 1983(i)568–569Google Scholar
  322. 323.
    Moutamat SC, Cusack BJ, Vestal RE: Managément of drug therapy in the elderly. N Engl J Med 1989 (321):303–309CrossRefGoogle Scholar
  323. 324.
    Bricker H: Estimate of overall treatment results in acute nonlymphocytic leukaemia based on age-specific rates of incidence and of complete remission. Cancer Treat Rep 1985 (69):5–11Google Scholar
  324. 325.
    Cheson BD, Jasperse DM, Simon R, Friedman MA: A critical appraisal of low-dose cytosmi arabinoside in patients with acute non-lymphocytic leukaemia and myelodysplastic syndromes. J Clin Oncol 1986 (4):1857–1864PubMedGoogle Scholar
  325. 326.
    Powell BL, Capizzi RL, Muss HB: Low dose Ara-C therapy for acute myelogenous leukaemia in elderly patients. Leukemia 1989 (3):23–28PubMedGoogle Scholar
  326. 327.
    Sebban C, Archimband Coiffier B et al: Treatment of acute myeloid leukemia in elderly patients. Cancer 1988(61):227–231PubMedCrossRefGoogle Scholar
  327. 328.
    Walters RS, Kantavjian HM, Keating MJ et al: Intensive treatment of acute leukemia in adults 70 years of age and older. Cancer 1987 (60):149–155PubMedCrossRefGoogle Scholar
  328. 329.
    Berman E, Witties RE, Leyland-Jones B et al: Phase I and clinical pharmacology studies of intravenous and oral administration of 4-demethoxydaunorubicin in patients with advanced cancer. Cancer Res 1983 (43):6096–6101PubMedGoogle Scholar
  329. 330.
    Resegotti L, Mandelli F, Amadori S et al: An Italian multicentre phase III trial of Idarubicin plus Ara-C vs daunorubicin plus Ara-C in elderly patients with acute non-lymphoid leukaemia. Proc 4th Int Symp Ther Acute Leuk, Rome 1987 pp 42–49Google Scholar
  330. 331.
    Waterhouse J, Muir C, Shanmugaratnum K et al: Cancer incidence in five continents. WHO 1982 (IV), IARC LyonGoogle Scholar
  331. 332.
    Young YH, Miller RW: Incidence of malignant tumors in US children. J Pediatr 1975 (86):254PubMedCrossRefGoogle Scholar
  332. 333.
    Bennett JM, Catovsky D, Daniel MT et al: The morphological classification of acute lymphoblastic leukemia: concordance among observers and clinical correlations. Br J Haematol 1981 (47):553–561PubMedCrossRefGoogle Scholar
  333. 334.
    Mauer AM and Simone JV: The current status of the treatment of childhood acute lymphoblastic leukaemia. Cancer Treat Rev 1976 (3):17–41PubMedCrossRefGoogle Scholar
  334. 335.
    Report to the Council by the Working Party on Leukaemia in Childhood: Improvement in treatment for children with acute lymphoblastic leukaemia. The Medical Research Council UKALL Trials 1972–84, Lancet 1986 (i):408–411Google Scholar
  335. 336.
    Bloomfield CD: Classification and prognosis of acute lymphoblastic leukaemia. Prognostic Clinical and Biological Research 1981 (58):167–183Google Scholar
  336. 337.
    Lilleyman JS, Hann IM, Stevens RF, Eden OB and Richards SM: French American British (FAB) morphological classification of childhood leukaemia and its clinical importance. J Clin Path 1986 (39):998–1002PubMedCrossRefGoogle Scholar
  337. 338.
    Bloomfield CD, Goldman AI, Alimena G et al: Chromosomal abnormalities identify high risk and low risk patients with acute lymphoblastic leukaemia. Blood 1986 (67):415–420PubMedGoogle Scholar
  338. 339.
    Robinson LL, Nesbit ME, Sather HN and Hammond GD: Assessment of the interrelationship of prognostic factors in childhood acute lymphoblastic leukaemia. A report from Children’s Cancer Study Group. Am J Pediat Haemat Oncol 1986(2):5–3Google Scholar
  339. 340.
    Baccarani M, Corbelli G, Amadori S et al: Adolescent and adult acute lymphoblastic leukaemia: prognostic features and outcome of therapy. A study of 293 patients. Blood 1982 (60): 677–684PubMedGoogle Scholar
  340. 341.
    Bloomfield CD: The clinical relevance of lymphocytic surface markers in adult acute lymphoblastic leukaemia. In: CD Bloomfield (ed) Adult Leukaemias. Martinus Nijhoff Publ, The Hague 1982 pp 265–308CrossRefGoogle Scholar
  341. 342.
    Garay G, Pavlovsky S, Eppinger-Helft M, Cavagnaro F et al: Long term survival in acute lymphoblastic leukaemia: evaluation of prognostic factors. Proc Am Soc Clin Oncol 1982 (1):137 (abstr)Google Scholar
  342. 343.
    Mertelsmann R, Moore MAS and Claubron B: Leukaemia cell phenotype and prognosis: an analysis of 519 adults with acute leukaemia/ Blood Cells 1982 (8):561–583PubMedGoogle Scholar
  343. 344.
    Hoelzer D, Thiel E, Loffler H, Buchner T et al: Prognostic factors in multicentre study for treatment of acute lymphoblastic leukaemia in adults. Blood 1988 (71):123–131PubMedGoogle Scholar
  344. 345.
    Shuster JJ, Falletta JM, Pullen DJ: Prognostic factors in childhood T-cell acute lymphoblastic leukemia: A pediatric oncology group study. Blood 1990(75):166–173PubMedGoogle Scholar
  345. 346.
    Clarkson B, Ellis S, Little C, Gee T et al: Acute lymphoblastic leukaemia in adults. Semin Oncol 1985(12):160–179PubMedGoogle Scholar
  346. 347.
    Henze G, Langermann HJ, Ritter J, Schellong and Riehm H: Treatment strategy for different risk groups in childhood acute lymphoblastic leukaemia: a report from the BFM Study Group. Haematol Blood Transf 1981 (26):87–93Google Scholar
  347. 348.
    Gingrich RD, Burns CP, Armitage JO et al: Long term relapse-free survival in adult acute lymphoblastic leukaemia. Cancer Treat Rep 1985 (69):153–160PubMedGoogle Scholar
  348. 349.
    Sobol RE, Royston I, Le Bien TW, Minowada J et al: Adult acute lymphoblastic leukaemia phenotypes defined by monoclonal antibodies. Blood 1985 (65):730–735PubMedGoogle Scholar
  349. 350.
    Van den Berghe H: Cytogenetics in leukaemia. In: Whittaker J and Delamore IW (eds) Leukaemia. Blackwell Scient Publ, Oxford 1987 pp 137–151Google Scholar
  350. 351.
    Secker-Walker LM, Lawler SD and Hardisty RM: Prognostic implications of chromosomal findings in acute lymphoblastic leukaemia at diagnosis. Br Med J 1978 (2):1529–1530PubMedCrossRefGoogle Scholar
  351. 352.
    Swansbury GJ, Secker-Walker LM, Lawler SD et al: Chromosomal findings in acute lymphoblastic leukaemia of childhood: an independent prognostic factor. Lancet 1981 (ii):249–250CrossRefGoogle Scholar
  352. 353.
    Williams DL, Tsiatis A, Braden GM et al: Diagnostic importance of chromosome numbers in 136 untreated children with acute lymphoblastic leukaemia. Blood 1981 (60):864–871Google Scholar
  353. 354.
    Frei E III, Karan M, Levin R and Freireich EJ: The effectiveness of combinations of antileukaemic agents in inducing and maintaining remission in children with acute leukaemia. Blood 2965 (26):642–656PubMedGoogle Scholar
  354. 355.
    Freireich EJ, Gehan E, Frei E et al: The effect of 6-mercaptopurine on the duration of steriod-induced remissions in acute leukaemia: a model for evaluation of other potentially useful therapy/ Blood 1963 (21):699–716Google Scholar
  355. 356.
    Selawry OS and Frei E III: Prolongation of remission in acute lymphocytic leukaemia by alteration in dose schedule and route of administration of methotrexate/ Clin Res 1964 (2):230–235Google Scholar
  356. 357.
    Pinkel D: Curing children with leukaemia. Charles F Kettering Prize Oration 1986. Cancer 1987 (59):1683–1691PubMedCrossRefGoogle Scholar
  357. 358.
    Lennard L and Lilleyman JS: Are children with lympoblastic leukaemia given enough 6-mercaptopurine? Lancet 1987 (ii):785–787CrossRefGoogle Scholar
  358. 359.
    Lennard L and Lilleyman JS: Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukaemia. J Clin Oncol 1989(7):1816–1823PubMedGoogle Scholar
  359. 360.
    DeVita VT: Dose response is alive and well. J Clin Oncol 1986 (4):1157–1159PubMedGoogle Scholar
  360. 361.
    Riehm H, Gadner H and Henze G: Results and significance of six randomised trials in four consecutive ALL-BFM studies. Haematol Blood Transf 1990 (33):439–450Google Scholar
  361. 362.
    Buchner T, Henze G, Hoffmann J, Reiter A et al: Central nervous system relapse prevention in 1165 standard risk children with acute lymphoblastic leukaemia in five BFM finals. Haematol Blood Transf 1990 (33):500–503Google Scholar
  362. 363.
    Nesbit ME, Sather HN, Robison LL et al: Presymptomatic central nervous system therapy in previously untreated childhood lymphoblastic leukaemia: Comparison of 1800 Rads and 2400 Rads. Lancet 1981 (i):461–465CrossRefGoogle Scholar
  363. 364.
    Gimema Cooperative Group: Gimema ALL0183: a multicentre study on adult acute lymphoblastic leukaemia in Italy. Br J Haematol 1989 (71):377–386Google Scholar
  364. 365.
    Byrd RL, Chatten J, Raney RB, Littman P et al: Testicular leukaemia incidence and management results. Med Pediat Oncol 1981 (9):493–500CrossRefGoogle Scholar
  365. 366.
    Land VJ, Berry DH, Henson J et al: Long term survival in childhood acute leukaemia: “late” relapses. Med Pediat Oncol 1979 (7):19–24CrossRefGoogle Scholar
  366. 367.
    Baum E, Sather H, Nachman J et al: Relapse rates following cessation of chemotherapy during complete remission of acute lymphoblastic leukaemia. Med Pediat Oncol 1979 (7):25–34CrossRefGoogle Scholar
  367. 368.
    Medical Research Council: Testicular disease in acute lymphoblastic leukaemia in childhood. Br Med J 1978: (1):334–338CrossRefGoogle Scholar
  368. 369.
    Miller DR, Leikin SL, Albo VC et al: Three versus five years of maintenance therapy are equivalent in childhood acute lymphoblastic leukemia: A report from the childrens Cancer Study Group. J Clin Oncol 1989 (7):316–325PubMedGoogle Scholar
  369. 370.
    Nesbit ME, Robison LL, Ortega JA et al: Testicular relapse in childhood acute lymphoblastic leukaemia: association with pretreatment patient characteristics and treatment. Cancer 1980 (45):2009–2016PubMedCrossRefGoogle Scholar
  370. 371.
    Sullivan MP, Perez CA, Herson J et al: Radiotherapy (2500) Rads) for testicular leukaemia, local control and subsequent clinical events: A South Western Oncology Group Study. Cancer 1980 (46):508–515PubMedCrossRefGoogle Scholar
  371. 372.
    Oakhill A, Mainwaring D, Hill FG et al: Management of leukaemic infiltration of the testis. Arch Dis Child 1980(55):564–566PubMedCrossRefGoogle Scholar
  372. 373.
    Tiedemann K, Chessells JM and Sandland RM: Isolated testicular relapse in boys with acute lymphoblastic leukaemia: treatment and outcome. Br Med J 1982 (285):1614–1616CrossRefGoogle Scholar
  373. 374.
    Pui C-H, Dahl GV, Bowman WP et al: Elective testicular biopsy during chemotherapy for childhood leukaemia is of no clinical value. Lancet 1985(ii):410–412CrossRefGoogle Scholar
  374. 375.
    Eden DB: Extramedullary leukaemia. In: Willoughby M and Siegel B (eds) Paediatric Haematology and Oncology. Butterworth Med Rev 1982 pp 47–79Google Scholar
  375. 376.
    Burchenal JH: Long term survivors in acute leukaemia and Burkitt’s tumour. Cancer 1968 (21):595–599PubMedCrossRefGoogle Scholar
  376. 377.
    Medical Research Council: Duration of therapy in childhood ALL. Med Pediat Oncol 1982 (10):511–520Google Scholar
  377. 378.
    George SL, Aur RJA, Mauer AM and Simone JV: A reappraisal of the results of stopping therapy in childhood leukaemia. N Engl J Med 1979 (300):269–273PubMedCrossRefGoogle Scholar
  378. 379.
    Nesbit ME, Sather HN, Robinson LL et al: Randomised study of 3 years versus 5 years chemotherapy in childhood acute lymphoblastic leukaemia. J Clin Oncol 1983 (1):308–316PubMedGoogle Scholar
  379. 380.
    Koren G, Ferranzani G, Hassan S et al: Systemic exposure to mercaptopurine as a prognostic factor in acute lymphocytic leukemia in children. N Engl J Med 1990 (323):17–21PubMedCrossRefGoogle Scholar
  380. 381.
    Woods WG, Nesbit ME, Ramsay NKC et al: Intensive therapy followed by bone marrow transplantation for patients with acute lymphoblastic leukaemia in second or subsequent remission: determination of prognostic factors (A report from the University of Minnesota Bone Marrow Transplantation Team). Blood 1983 (61):1182–1189PubMedGoogle Scholar
  381. 382.
    Rivera GK, Buchanan G, Boyett JM et al: Intensive retreatment of childhood acute lympoblastic leukaemia in first bone marrow relapse: a paediatric oncology group study N Engl J Med 1986 (315):273–278PubMedCrossRefGoogle Scholar
  382. 383.
    Chessells JM, Leiper AD, Plowman PN et al: Bone marrow transplantation has a limited role in prolonging second marrow remission in childhood lymphoblastic leukaemia. Lancet 1986 (i):1239–1241CrossRefGoogle Scholar
  383. 384.
    Butturini A, Bortin MM Rivera G et al: Which treatment for childhood acute lymphoblastic leukaemia in second remission? Lancet 1987 (i):429–432CrossRefGoogle Scholar
  384. 385.
    Saunders JE, Thomas ED, Buckner CD et al: Marrow transplantation for children with acute lymphoblastic leukaemia in second remission Blood 1987(70):324–326Google Scholar
  385. 386.
    Henze G, Fengler R, Hartmann R et al: BFM Group treatment results in relapsed childhood acute lymphoblastic leukemia. Haematol Blood Transf 1990(33):619–626Google Scholar
  386. 387.
    Steinberz PG, Gaynon P, Miller DR et al: Improved disease free survival of children with acute lymphoblastic leukaemia at high risk of early relapse with the New York Regime — a new intensive therapy protocol: a report from the Children’s Cancer Study Group. J Clin Oncol 1986 (4):744–752Google Scholar
  387. 388.
    Haas OA, Mor W, Gadner H and Bartram CR: Treatment of Ph-positive acute lymphoblastic leukaemia with alpha- Interferon. Leukaemia 1987 (i):555 (letter)Google Scholar
  388. 389.
    Swanson G, Hu E, Sklar J et al: A prospective assessment of residual clonal disease in adult ALL utilising immunoglobulin gene rearrangement (IgR). Blood 1985 (66):246a (abstract)Google Scholar
  389. 390.
    Wright JJ, Poplack DG, Dakhshi A: Gene rearrangements as markers for clonal variation and minimal residual disease in acute lymphoblastic leukaemia. J Clin Oncol 1987 (5):735–741PubMedGoogle Scholar
  390. 391.
    Korsmeyer SJ: Antigen receptor genes as molecular markers for lymphoid neoplasms. J Clin Invest 1987 (79):1291–1295PubMedCrossRefGoogle Scholar
  391. 392.
    Lee MS Chang KS Caanillas et al: Detection of minimal residual cells carrying the t(14:18) by DNA sequence amplification/ Science 1987 (23):175–178CrossRefGoogle Scholar
  392. 393.
    Estrov Z, Grimberger T, Dube ID et al: Detection of residual acute lymphoblastic leukaemia cells in cultures of bone marrow obtained during remission. N Engl J Med 1986 (315):538–542PubMedCrossRefGoogle Scholar
  393. 394.
    Lee MS, Chang KS, Freireich EJ et al Detection of immunal residual bcr/abl transcripts by a modified polymerase chain reaction. Blood 1988 (72):893–897PubMedGoogle Scholar
  394. 395.
    Zehnbauer BA, Pardoll DM, Burke PJ et al: Immunoglobulin gene rearrangements in remission bone marrow specimens from patients with acute lymphoblastic leukaemia. Blood 1986 (67):835–838PubMedGoogle Scholar
  395. 396.
    Delfau M-H, Kerckaert J-P, d’Hooghe MC et al: Detection of minimal residual disease in chronic myeloid leukaemia patients after bone marrow transplantation by polymerase chain reaction. Leukemia 1990 (4): 1–5PubMedGoogle Scholar
  396. 397.
    Bregni M, Siena S, Neri A et al: Minimal residual disease in acute lymphoblastic leukemia detected by immune selection and gene rearrangement analysis. J Clin Oncol 1989 (7):338–343PubMedGoogle Scholar
  397. 398.
    Robison LL, Nesbit ME, Sather HN et al: Height of children successfully treated for acute lymphoblastic leukaemia. A report from the Late Effects Study Group of the Childrens Cancer Study Group. Med Pediatr Oncol 1985 (13):14–21PubMedCrossRefGoogle Scholar
  398. 399.
    Kirk JA, Raghupathy P, Stevens MM et al: Growth failure and growth hormone deficiency after treatment for acute lymphoblastic leukaemia. Lancet 1987 (i): 190–193CrossRefGoogle Scholar
  399. 400.
    Ouigley C, Cowell C, Jimenez M et al: Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukaemia. N Engl J Med 1989 (321):143–151CrossRefGoogle Scholar
  400. 401.
    Civin CI: Reducing the cost of the cure in childhood leukaemia. N Engl J Med 1989 (321):185–187 (editorial)PubMedCrossRefGoogle Scholar
  401. 402.
    Clayton PE, Shalet SM, Morris-Jones PH and Price DA: Growth in children treated for acute lymphoblastic leukaemia. Lancet 1988 (i):460–462CrossRefGoogle Scholar
  402. 403.
    Leiper AD, Wheeler K and Chessells JM: Growth in children treated for acute lymphoblastic leukaemia. Lancet 1988 (i):943 (letter)CrossRefGoogle Scholar
  403. 404.
    Wheeler K, Leiper AD, Jannoun L and Chessells JM: Medical cost of curing childhood acute lymphoblastic leukaemia. Br Med J 1988 (296):162–166CrossRefGoogle Scholar
  404. 405.
    Hamre MR, Robinson LL, Nesbit ME et al: Effects of radiation on ovarian function in long term survivors of childhood acute lymphoblastic leukemia: A report from the Children’s Cancer Study Group. J Clin Oncol 1987 (5) 1759–1765PubMedGoogle Scholar
  405. 406.
    Ise T, Kishi K, Imashuku S et al: Testicular histology and function following long-term chemotherapy of acute leukemia in children and outcome of the patients who received testicular biopsy. Am J Pediat Haematol Oncol 1986 (8):288–293CrossRefGoogle Scholar
  406. 407.
    Jannoun L: Are cognitive and educational development affected by the age at which prophylactic therapy is given in acute lymphoblastic leukaemia? Arch Dis Childh 1983 (58):953–958PubMedCrossRefGoogle Scholar
  407. 408.
    Mulhern RK, Ochs J and Fairclough D: Intellectual and academic achievement status after CNS relapse: a retrospective analysis of 40 children treated for acute lymphoblastic leukaemia. J Clin Oncol 1987 (5):933–940PubMedGoogle Scholar
  408. 409.
    Maguire P, Comaroff J, Ramsell PJ and Morris-Jones PH: Psychological and social problems in families of children with leukaemia. In: Morris Jones PH (ed) Topics in Paediatrics. I. Haematology and Oncology. Pitman Medical, Tunbridge Wells 1979 pp 141–149Google Scholar
  409. 410.
    O’Hare AE, Mclnnes A, Clarke M and Eden OB: The latency of visual evoked potential as an index of myelin disturbance in children treated for acute lymphoblastic leukaemia. Clin Electroencephalography 1987 (18):68–71Google Scholar
  410. 411.
    Zarrabi MH, Rosner F, Grunwald HW: Second neoplasms in acute lymphoblastic leukaemia. Cancer 1983 (52):1712–1719PubMedCrossRefGoogle Scholar
  411. 412.
    Rosner K and Grunwald HW: Association of T-cell acute lymphoblastic leukaemia and histiocytic medullary reticulosis. Am J Med 1984 (77):910–914PubMedCrossRefGoogle Scholar
  412. 413.
    Pui CH, Behm FG and Raimondi SC: Secondary acute myeloid leukaemia in children treated for acute lymphoid leukaemia. N Engl J Med 1989 (321):136–142PubMedCrossRefGoogle Scholar
  413. 414.
    Albo V, Miller D, Leiken S et al: Nine brain tumours as a late effect in children ‘cured’ of acute lymphoblastic leukaemia (ALL) from a single protocol/ Proc Am Soc Clin Oncol 1985 (4):172 (abstr)Google Scholar
  414. 415.
    Green DM (ed) Long Term Complications of Therapy for Cancer in Childhood and Adolescence. The Johns Hopkins University Press, Baltimore 1989 pp 171Google Scholar
  415. 416.
    Fialkow PJ: Clonal development and stem cell origin of leukaemias and related disorders. Gunz FW and Henderson ES (eds) Leukaemia 4th Ed. Grune & Stratton, New York 1983 pp 63–76Google Scholar
  416. 417.
    Nowell PC and Hungerford DA: A minute chromosome in human chronic granulocytic leukaemia. Science 1960 (132):1497 (abstract from Nat Acad Sci, autumn meeting)Google Scholar
  417. 418.
    Canellos GP: Chronic granulocytic leukaemia. Med Clin North Am 1976 (60):1001–1018PubMedGoogle Scholar
  418. 419.
    Kurzrock R, Shtalrid M, Gutterman JU, Talpaz M: The molecular diagnostics of chronic myelogenous leukemia and Philadelphia positive acute leukemia. Cancer Cells 1989 (7):9–13Google Scholar
  419. 420.
    Shtalrid M, Talpaz M, Blick M et al: Philadelphianegative chronic myelogenous leukemia with breakpoint cluster rearrangement: Molecular analysis, clinical characteristics and response to therapy. J Clin Oncol 1988 (6):1569–1575PubMedGoogle Scholar
  420. 421.
    Bartram CR, Kleihauer E, de Klein A et al: C-abl and bcr are rearranged in a Ph-negative patient. EMBO J 1985 (4):683–686PubMedGoogle Scholar
  421. 422.
    Wiedemann LM, Karhi KK, Shivjim KK et al: The correlation of breakpoint cluster region rearrangement and P210 bcr/abl expression with morphological analysis of Ph-negative chronic myeloid leukemia and other myeloproliferative diseases. Blood 1988 (71):349–355PubMedGoogle Scholar
  422. 423.
    Bartram CR: Rearrangement of the C-abl and bcr genes in Ph-negative CML and Ph- CML and Ph-positive acute leukemia. Leukemia 1988 (2):63–64PubMedGoogle Scholar
  423. 424.
    Van der Plas DC, Hermans ABC, Soekarman D et al: Cytogenetic and molecular analysis in Philadelphia negative CML. Blood 1989 (73):1038–1044PubMedGoogle Scholar
  424. 425.
    Kurzrock R, Kantarjian M, Shtalrid M: Philadelphia chromosome negative chronic myelogenous leukemia without breakpoint cluster rearrangements: A chronic myeloid leukemia with a distinct clinical course. Blood 1990 (75):445–452PubMedGoogle Scholar
  425. 426.
    Goldman JM, Grooveld G, Baltimore D et al: Chronic myelogenous leukemia: the unfolding saga. Leukemia 1990 (4):163–167PubMedGoogle Scholar
  426. 427.
    Rassool F, Martiat P, Taj A et al: Interstitial insertion of varying amounts of abl-containing genetic material into chromosome 22 in Ph-negative CML. Leukemia 1990 (4):273–277PubMedGoogle Scholar
  427. 428.
    Van Etten R, Jackson P, Baltimore D: The mouse type IV c-abl gene product is a nuclear protein and activation of transforming ability is associated with cytoplasmic localisation. Cell 1989 (58):669–678PubMedCrossRefGoogle Scholar
  428. 429.
    Jackson P, Baltimore D: N-terminal mutations activate the leukemogenic potential of the myristoylated form of c-abl. EMBO J 1989 (8):449–456PubMedGoogle Scholar
  429. 430.
    Daley GQ, Van Etten RA, Baltimore D: Induction of chronic myelogenous leukemia by the P210 bcr/abl gene of the Philadelphia chromosome. Science 1990(247):824–830PubMedCrossRefGoogle Scholar
  430. 431.
    Hughes T, Janssen JWG, Morgan G et al: False positive results with PCR to detect leukaemia-specific transcript. Lancet 1990 (i):1037–1038CrossRefGoogle Scholar
  431. 432.
    Karanas A and Silver RT: Characteristics of the terminal phase of chronic granulocytic leukaemia. Blood 1968 (32):445–459PubMedGoogle Scholar
  432. 433.
    Theologides A: Unfavourable signs in patients with chronic myelocytic leukaemia. Ann Int Med 1972 (76):95–99PubMedGoogle Scholar
  433. 434.
    Shaw MT: Clinical and haematological manifestations of the terminal phase. In: Shaw MT (ed) Chronic Granulocytic Leukaemia. Praeger Publishers, Eastbourne 1982 pp 169–188Google Scholar
  434. 435.
    Sokal JE, Cox EB and Baccarani M et al: Prognostic discrimination in “good risk” chronic granulocytic leukaemia. Blood 1984 (63):789–799PubMedGoogle Scholar
  435. 436.
    Sokal JE, Baccarani M, Tura S et al: Prognostic discrimination among younger patients with chronic granulocytic leukaemia: relevance to bone marrow transplantation. Blood 1985 (66):1352–1357PubMedGoogle Scholar
  436. 437.
    Sokal JE: Prognosis in chronic myeloid leukaemia: biology of the disease vs treatment. In: Goldman JM (ed) Bailliere’s Clinical Haematology (Chronic Myeloid Leukaemia). Bailliere Tindall 1987 (1):907–929Google Scholar
  437. 438.
    Simon W, Segel GB, Lichtman A: Upper and lower time limits in the decision to recommend marrow transplantation for patients with chronic myelogenous leukaemia. Br J Haematol 1988 (70):31–36PubMedCrossRefGoogle Scholar
  438. 439.
    Italian Cooperative Study Group on Chronic Myeloid Leukaemia. Timing of the haematological diagnosis of Ph positive chronic myeloid leukaemia. Eur J Haematol 1987 (38):75–79CrossRefGoogle Scholar
  439. 440.
    Italian Cooperative Study Group on Chronic Myeloid Leukaemia. Prospective confirmation of a prognostic classification for Ph-positive chronic myeloid leukaemia. Br J Haematol 1988 (69):436–466Google Scholar
  440. 441.
    Pusey WA: Report of cases treated with roentgen rays. JAMA 1902 (38):911–919CrossRefGoogle Scholar
  441. 442.
    Forkner CE and Scott TF: Arsenic as a therapeutic agent in chronic myelogenous leukaemia. JAMA 1931 (97):3–5CrossRefGoogle Scholar
  442. 443.
    Galton DAG: Myleran in chronic myeloid leukaemia: results of treatment. Lancet 1953 (i):208–213CrossRefGoogle Scholar
  443. 444.
    Haddow A and Timmis GM: Myleran in chronic myeloid leukaemia: chemical constitution and biological action. Lancet 1953 (i):207–208CrossRefGoogle Scholar
  444. 445.
    Burns WA, McFarland W and Matthews MJ: Toxic manifestations of busulfan therapy. Med Ann DC 1971 (40):567–569PubMedGoogle Scholar
  445. 446.
    Allan NC, Duvall E, Stockdill G: Combination therapy for chronic granulocytic leukaemia. Lancet 1978 (ii):523 (letter)CrossRefGoogle Scholar
  446. 447.
    Key NS, Emerson PM, Allan NC, Kelly PMA et al: Oesophageal varices associated with busulphan-thioguanine combination therapy for chronic myeloid leukaemia. Lancet 1987 (ii):1050–1052CrossRefGoogle Scholar
  447. 448.
    Dresler WF and Stein R: Veber den Hydroxylharnstoff. Justus Liebig’s Ann Chem Pharm 1869 (150):242–245CrossRefGoogle Scholar
  448. 449.
    Kennedy BJ and Yarboro JW: Metabolic and therapeutic effects of hydroxyurea in chronic myeloid leukaemia. JAMA 1966 (195):1038–1043PubMedCrossRefGoogle Scholar
  449. 450.
    Bolin RW, Robinson WA, Sutherland J and Hamman RF: Busulfan versus hydroxyurea in long-term therapy of chronic myelogenous leukaemia. Cancer 1982(50):1683–1686PubMedCrossRefGoogle Scholar
  450. 451.
    Talpaz M, McCredie KB, Mavligit GM and Gutterman JV: Leukocytic interferon — induced myeloid cytoreduction in chronic myelogenous leukaemia. Blood 1983 (62):689–692PubMedGoogle Scholar
  451. 452.
    Cantell K and Hirvonnen S: Large scale production of human leucocyte interferon containing 10 units per ml. J Gen Virol 1978 (39):541–543PubMedCrossRefGoogle Scholar
  452. 453.
    Neumann HA and Fauser AA: Effect of interferon on pluripotent haemopoietic progenitors (CFU-GEMM) derived from human bone marrow. Exp Haematol 1982(10):587–590Google Scholar
  453. 454.
    Williams CK, Svet-Moldavskaya I and Vilcek J: Inhibitory effects of human leucocyte and fibroblast interferons on normal and chronic myelogenous leukaemia granulocytic progenitor cells. Oncology 1981 (38):356–360PubMedCrossRefGoogle Scholar
  454. 455.
    Talpaz M, Kantarjian HM, McCredie K et al: Hematologic remission and cytogenetic improvement induced by recombinant human Interferon alpha in chronic myelogenous leukaemia. N Engl J Med 1986 (314):1065–1069PubMedCrossRefGoogle Scholar
  455. 456.
    Kantarjian HM, Talpaz M, Kurzrock R and Keating MJ: Intensive combination chemotherapy and interferons in the management of chronic myelogenous leukaemia. Acta Haemat 1987 (78 Suppl 1):70–74PubMedCrossRefGoogle Scholar
  456. 457.
    Hardisty RM, Speed DE, Till M: Granulocytic leukaemia in childhood. Br J Haematol 1964 (10):551–556PubMedCrossRefGoogle Scholar
  457. 458.
    Weatherall DJ, Brown MJ: Juvenile chronic myeloid leukaemia. Lancet 1970 (i):526CrossRefGoogle Scholar
  458. 459.
    Fox AM: Case of juvenile chronic myeloid leukaemia. Lancet 1970 (i):368–369CrossRefGoogle Scholar
  459. 460.
    Shapira Y, Polliack A, Cividalli G, Rachmilewitz EA: Juvenile chronic myeloid leukemia with fetal erythropoiesis. Cancer 1972 (30):353–357PubMedCrossRefGoogle Scholar
  460. 461.
    Maurer HS, Vida LN, Honig GR: Similarities of the erythrocytes in juvenile chronic myelogenous leukemia and fetal erythrocytis. Blood 1972 (39):778–784PubMedGoogle Scholar
  461. 462.
    Goldman JM and Baughan ASJ: Chronic granulocytic leukaemia. In: Goldman JM and Preisler HD (eds) Leukemias. Butterworth International Medical Reviews 1984 pp 239–265Google Scholar
  462. 463.
    Allan NC, Shepherd PCA: Treatment of chronic myeloid leukaemia. In: Goldman JM (ed) Bailliere’s Clinical Haematology 1. Bailiiere Tindall 1987 (1):1031–1054Google Scholar
  463. 464.
    Janossy G, Woodruff RK, Pippard MJ et al: Relation of “Lymphoid” phenotype and response to chemotherapy incorporating vincristine-prednisolone in the acute phase of PL-positive leukaemia. Cancer 1979 (43):426–434PubMedCrossRefGoogle Scholar
  464. 465.
    Griffin JD, Ttodd RF, Ritz J et al: Differentiation patterns in the blastic phase of chronic myeloid leukemia. Blood 1983 (61):85–91PubMedGoogle Scholar
  465. 466.
    Muehleck SD, McKenna RW and Arthur DC: Transformation of chronic myelogenous leukemia: clinical morphologic and cytogenetic features. Am J Clin Path 1984 (82):1–14PubMedGoogle Scholar
  466. 467.
    Office of Population Censuses and Surveys. Cancer Statistics. Registration series in B1 No 14 and mortality statistics DH2 No 9. HMSO, London 1982Google Scholar
  467. 468.
    Linet MS and Blattner WA: The epidemiology of chronic lymphatic leukaemia. In: Polliack A and Catovsky D (eds) Chronic Lymphatic Leukaemia. Harwood Academic Publishers, New York 1988 pp 11–32Google Scholar
  468. 469.
    Sawitsky A and Rai K: The chronic lymphoid leukaemias. In: Whittaker J and Delamore IW (eds) Leukaemia. Blackwell Science Publishers, Oxford 1983 pp 386–406Google Scholar
  469. 470.
    Hamblin TJ: Chronic lymphocytic leukaemia. Baillere’s Clin Haematol 1987 (i) :449–491CrossRefGoogle Scholar
  470. 471.
    Casey TD: Chronic lymphatic leukaemia in a child presenting at the age of 2 years and 8 months. Austr Ann Med 1968 (17):70–74Google Scholar
  471. 472.
    Gunz FW: Epidemiology of leukaemia. In: Gunz FW and Henderson ES (eds) Leukaemia 4th Ed. Grune & Stratton, New York 1983 pp 27–28Google Scholar
  472. 473.
    Uchiyama T, Yodoi J et al: Adult T-cell leukaemia: clinical and haematological features of 16 cases. Blood 1977 (50):481–492PubMedGoogle Scholar
  473. 474.
    Hattori T, Uchiyama T, Toibana T, Takatsuki K and Uchino H: Surface phenotype of Japanese adult T-cell leukaemia cells characterised by monoclonal antibodies. Blood 1981 (58):645–647PubMedGoogle Scholar
  474. 475.
    Blattner WA, Strober W, Muchmore AV, Blaese RM et al: Familial chronic lymphocytic leukaemia. Immunologic and cellular characterisation. Annal Int Med 1976 (84):554–557Google Scholar
  475. 476.
    Williams RC, Erickson JL, Polesky HF, Swann WR: Studies of monoclonal immunoglobulins (M-components) in various kindreds. Ann Int Med 1967 (67):309–327PubMedGoogle Scholar
  476. 478.
    Bennett JM, Catovsky D, Daniel M-T, Flandrin G et al: Proposals for the classification of chronic (mature) B and T lymphoid leukaemias. J Clin Pathol 1989 (42):567–584PubMedCrossRefGoogle Scholar
  477. 479.
    Rai KR, Sawitsky A, Cronkite KP, Chanana EP et al: Clinical staging of chronic lymphocytic leukaemia. Blood 1975 (46):219–234PubMedGoogle Scholar
  478. 480.
    Binet JL, Catovsky D, Chandra P et al: Report from the International Workshop on CLL Chronic Lymphatic Leukaemia: proposals for a revised prognostic staging system. Br J Haematol 1981 (48):365–367CrossRefGoogle Scholar
  479. 481.
    Sweet DC Jr, Golomb HM and Ultmann JE: The clinical features of chronic lymphocytic leukaemia. Clinics in Haematology 1977 (6):185–202PubMedGoogle Scholar
  480. 482.
    Ebbe S, Wittels B and Damashek W: Autoimmune thrombocytopenic purpura (ITP type) with chronic lymphocytic leukaemia. Blood 1962 (19):23–27PubMedGoogle Scholar
  481. 483.
    Evans RS, Takahaski K, Duane RT et al: Primary thrombocytopenic purpura and acquired haemolytic anaemia. Arch Int Med 1951 (87):48–65CrossRefGoogle Scholar
  482. 484.
    Kaden BR, Rosse WF and Hauch TW: Immunothrombocytopenia in lymphoproliferative diseases. Blood 1979 (53):545–551PubMedGoogle Scholar
  483. 485.
    Hegde UM, Williams K, Devereux S, Bowes A et al: Platelet associated lgG and immune thrombocytopenia in lymphoproliferative and autoimmune disorders. Clin and Lab Haematol 1983 (5):9–15CrossRefGoogle Scholar
  484. 486.
    Rosse WF: The acquired haemolytic anaemias In: Hoffbrand AV and Lewis SM (eds) Postgraduate Haematology, 2nd Ed. W Heinemann Medical Books Ltd, Oxford 1981 pp 229–268Google Scholar
  485. 487.
    Lewis FB, Schwartz RS and Dameshek W: X-radiation and alkylating agents as possible “trigger” mechanisms in the autoimmune complications of malignant lymphoproliferative disease. Clin Exp Immunol 1966 (1):3–11PubMedGoogle Scholar
  486. 488.
    Ritch PS, Anderson T: Reversal of autoimmune hemolytic anemia associated with chronic lymphocytic leukemia following high-dose immunoglobulin. Cancer 1987 (60):2637–2740PubMedCrossRefGoogle Scholar
  487. 489.
    Rustagi P, Han T, Ziolkowski L et al: Antigranulocyte antibodies in chronic lymphocytic leukemia and other chronic lymphoproliferative disorders. Blood 1983 (62 Suppl 1):106 (abstract)Google Scholar
  488. 490.
    Abelhoff MD and Waterbury MD: Pure red cell aplasia and chronic lymphocytic leukaemia. Arch Int Med 1974 (134):721–724CrossRefGoogle Scholar
  489. 491.
    Miller DG: Patterns of immunological deficiency in leukaemias and lymphomas. Ann Int Med 1962 (57):703–715Google Scholar
  490. 492.
    Damashek W: Chronic lymphocytic leukaemia — an accumulative disease of immunologically incompetent lymphocytes. Blood 1967 (29): 566–584Google Scholar
  491. 493.
    Franklin EC: MU chain disease. Arch Int Med 1975 (135):71–72CrossRefGoogle Scholar
  492. 494.
    Rai KR and Sawitsky A: Studies in clinical staging, lymphocyte function and markers as an approach to the treatment of chronic lymphocytic leukaemia. Silber R et al (eds) Contemporary Haematology/Oncology. Plenum, New York 1981 pp 227–262Google Scholar
  493. 495.
    Shaw RK, Szwed D, Boggs DR et al: Infection and immunity in chronic lymphocytic leukaemia. Arch Int Med 1960 (106):467–478CrossRefGoogle Scholar
  494. 496.
    Miller DG and Karnofsky DA: Immunological factors and resistance to infection in chronic lymphatic leukaemia Am J Med 1961 (31):748–757PubMedCrossRefGoogle Scholar
  495. 497.
    Cone L and Uhr JW: Immunological deficiency disorders associated with chronic lymphocytic leukaemia and multiple myeloma. J Clin Invest 1964 (43):2241–2248PubMedCrossRefGoogle Scholar
  496. 498.
    Chapel H and Bunch C: Mechanisms of infection in chronic lymphocytic leukaemia. Semin Haematol 1987(24):291–296Google Scholar
  497. 499.
    Boggs DR, Sofferman SA, Wintrobe MM and Cartwright GE: Factors influencing the duration of survival in chronic lymphocytic leukaemia. Am J Med 1966 (40):243–254PubMedCrossRefGoogle Scholar
  498. 500.
    Manoharan A, Catovsky D, Lampert I A et al: Histiocytic medullary reticulosis complicating chronic lymphocytic leukaemia: malignant or reactive? Scand J Haematol 1981 (26):5–13PubMedCrossRefGoogle Scholar
  499. 501.
    Rai KR and Sawitsky A: Diagnosis and treatment of chronic lymphocytic leukaemia. In: Wiernik PH, Canellos GP, Kyle RA and Schiffer CA (eds) Neoplastic Diseases of the Blood. Churchill Livingstone, New York 1985 pp 105–120Google Scholar
  500. 502.
    Galton DAG: Chronic lymphocytic leukaemia: treatment. In: Goldman JM and Preisler HD (eds) Haematology/Leukaemias. Butterworths, London 1984 pp 299–321Google Scholar
  501. 503.
    Hansen MM: Chronic lymphocytic leukaemia: clinical studies based on 189 cases followed for a long time. Scand J Haemat 1973 (18):3–28Google Scholar
  502. 504.
    Catovsky D, Fooks J and Richards S: Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment on survival. Br J Haematol 1989 (72):141–149PubMedCrossRefGoogle Scholar
  503. 505.
    French Cooperative group on CLL: Two clinical trials in CLL and clinical staging. Bone Marrow Transpl 1989 (4):158Google Scholar
  504. 506.
    Sawitsky A, Rai KR, Glidewell O, Silver RT et al: Comparison of daily versus intermittent chlorambucil and prednisone therapy in the treatment of patients with chronic lymphocytic leukaemia. Blood 1977 (50):1049–1059PubMedGoogle Scholar
  505. 507.
    Freymann JG, Vancer JB, Marler EA and Meyer DG: Prolonged corticosteroid therapy of chronic lymphocytic leukaemia and the closely allied malignant lymphomas. Br J Haematol 1960 (6):303–323PubMedCrossRefGoogle Scholar
  506. 508.
    Galton DAG, Wiltshaw E, Szur L and Dacie JV: The use of chlorambucil and steroids in the treatment of chronic lymphocytic leukaemia. Br J Haematol 1961 (7):73–98PubMedCrossRefGoogle Scholar
  507. 509.
    Chastang C, Travade P, Benichou J, Dighiero G and Binet J-L: Patients accrual and interim statistical analysis in long-term clinical trials: the French chronic lymphocytic leukaemia CLL 80 protocol as a case study. Statistics in Medicine 1986(5):465–473PubMedCrossRefGoogle Scholar
  508. 510.
    Hansen MM, Anderson E, Christensen BE, Christiansen I et al: CHOP versus prednisolone + chlorambucil in chronic lymphocytic leukaemia: preliminary results of a randomised multicentre study. Nouv Rev Fr Hématol 1988 (30):433–436PubMedGoogle Scholar
  509. 511.
    French Cooperative Group: Effectiveness of CHOP regimen in advanced untreated chronic lymphocytic leukaemia. Lancet 1986 (i):1346–1349Google Scholar
  510. 512.
    French Cooperative Group on Chronic Lymphocytic Leukaemia: Long-term results of the CHOP regimen in stage C chronic lympocytic leukaemia. Br J Haematol 1989 (73):334–340CrossRefGoogle Scholar
  511. 513.
    Keating MJ, Scouros M, Murphy S and Kantarjian H et al: Multiple agent chemotherapy (POACH) in previously treated and untreated patients with chronic lymphocytic leukaemia. Leukaemia 1988(2):157–164Google Scholar
  512. 514.
    Rubin P, Bennett JM, Begg C, Bozdech MJ and Silber R: The comparison of total body irradiation vs chlorambucil and prednisone for remission induction of active chronic lymphocytic leukaemia: an ECOG study. Part I: Total body irradiation. Response and toxicity. Int J Rad Oncol Biol Physics 1981 (7):1623–1632CrossRefGoogle Scholar
  513. 515.
    Singh AK, Bates T, Wetherley-Mein G: A preliminary study of low-dose irradiation for the treatment of chronic lymphocytic and prolymphocyte leukaemia. Scand J Haematol 1986 (37):50–58PubMedCrossRefGoogle Scholar
  514. 516.
    Riscoe MK, Brouns MC, Fitchen JH Purine metabolism as a target for leukemia chemotherapy. Blood Rev 1989 (3):162–173PubMedCrossRefGoogle Scholar
  515. 517.
    Tseng WC, Derse D, Cheng YC et al: In vitro biological activity of 9-B-D arabinofuranosyl-2-fluoroadenine and the biological actions of its triphosphate on DNA polymerase and ribonucleotide reductase from HeLa cells. Mol Pharmacol 1982 (21):474–477PubMedGoogle Scholar
  516. 518.
    Leiby JM, Snider KM, Kraut EH, Metz EN et al: Phase II trial of 9-a-d-arabinofuranosyl-2-fluoradenine 5’monophosphate in non-Hodgkin’s lymphoma. Prospective comparison of responses with deoxycytidine kinase activity. Cancer Res 1987(47):2719–2722PubMedGoogle Scholar
  517. 519.
    Lee WW, Benitz A, Goodman A and Baker BR: Potential anticancer agents XL: synthesis of the B-anomer of 9-(d-arabino- furanosyl) adenine. J Am Chem Soc 1960 (82):2648–2649CrossRefGoogle Scholar
  518. 520.
    Boldt DH, von Hoff DD, Kuhn JG and Hersch M: Effects on human peripheral lymphocytes of in vivo administration of 9-a-d- arabinofuranosyl-2-fluoradenine-5’-monophosphate (NSC 312887), a new purine antimetabolite. Cancer Res 1984 (44):4661–4666PubMedGoogle Scholar
  519. 521.
    Keating MJ, Kantarjian H, Talpaz M and Redman J et al: Fludarabine: a new agent with major activity against chronic lymphocytic leukaemia Blood 1989 (74):19–25PubMedGoogle Scholar
  520. 522.
    Warrell RP Jr, Berman E: Phase I and II study of fludarabine phosphate in Leukaemia: therapeutic efficacy with delayed central nervous system toxicity J Clin Oncol 1986 (4):74–79PubMedGoogle Scholar
  521. 523.
    Harvey WH, Fleming TR, Beltran G et al: Phase II study of fludarabine phosphate in previously untreated patients with hepatoma: a Southwest Oncology Group Study. Cancer Treat Rep 1987 (71):1111–1112PubMedGoogle Scholar
  522. 524.
    Spriggs DR, Stopa E, Mayer RJ et al: Fludarabine phosphate (NSC212878) infusions for the treatment of acute leukemia: phase I and neuropathological study. Cancer Res 1986 (46):5953–5958PubMedGoogle Scholar
  523. 525.
    Merkel DE, Griffin NL, Kagan-Hallet K, von Hoff DD: Central nervous system toxicity with fludarabine. Cancer Treat Rep 1986 (70):1449–1450PubMedGoogle Scholar
  524. 526.
    Hamblin TJ, Abdul-Ahad AK, Gordon J and Stevenson FK et al: Preliminary evidence in treating lymphocytic leukaemia with antibody to immunoglobulin idiotypes on the cell surface. Br J Cancer 1980 (42):495–502PubMedCrossRefGoogle Scholar
  525. 527.
    Gordon J, Abdul-Ahad AK, Hamblin TJ and Stevenson FK: Barriers to successful immunotherapy with anti-idiotype antibody. Br J Cancer 1984 (49):547–557PubMedCrossRefGoogle Scholar
  526. 528.
    Ritz J and Schlossman SF: Utilisation of monoclonal antibodies in the treatment of leukaemia and lymphoma. Blood 1982 (59):1–11PubMedGoogle Scholar
  527. 529.
    Levy R and Miller RA: Biological and clinical implications of lymphocytic hybridisations: Tumour therapy with monoclonal antibodies. Ann Rev Med 1983(34):107–116PubMedCrossRefGoogle Scholar
  528. 530.
    Bertram JH, Gill PS, Levine AM, Boquiren D et al: Monoclonal antibody T101 in T-cell malignancies: a clinical, pharmacokinetic and immunologic correlation. Blood 1986 (68):752–761PubMedGoogle Scholar
  529. 531.
    Press OW, Appelbaum F, Ledbetter J, Martin PJ et al: Monoclonal antibody IF5 (anti-CD20) serotherapy of human B cell lymphomas. Blood 1987(69):584–591PubMedGoogle Scholar
  530. 532.
    Dyer MJS, Hale G, Hayhoe FGJ and Waldman H: Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: Influence of antibody isotype. Blood 1989 (73):1431–1439PubMedGoogle Scholar
  531. 533.
    Riechmann L, Clark MR, Waldmann H and Winter G: Reshaping human antibodies for therapy. Nature 1988(332):323–327PubMedCrossRefGoogle Scholar
  532. 534.
    Hale G, Dyer MJS, Clark MR and Phillips JM et al: Remission induction in non-Hodgkin’s lymphoma with the reshaped human monoclonal antibody CAMPATH-IH. Lancet 1988 (ii):1394–1399CrossRefGoogle Scholar
  533. 535.
    Galton DAG, Goldman JM, Wiltshaw E et al: Prolymphocytc leukaemia. Br J Haematol 1974 (27):7–23PubMedCrossRefGoogle Scholar
  534. 536.
    Melo J, Catovsky D and Galton DAG: The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia. I. Clinical and laboratory features of 300 patients and characterisation of an intermediate group. Br J Haematol 1986 (63):377–387PubMedCrossRefGoogle Scholar
  535. 537.
    Melo J, Catovsky D and Galton DAG: The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia. II. Patterns of evolution of “prolymphocytoid” transformation. Br J Haematol 1986 (64):77–86PubMedCrossRefGoogle Scholar
  536. 538.
    Melo J, Wandle J, Chitty M and England J: The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia. III. Evaluation of cell size by morphology and volume measurements. Br J Haematol 1986 (64):469–478PubMedCrossRefGoogle Scholar
  537. 539.
    Melo J, Catovksy D, Gregory WM and Galton DAG: The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia. IV. Analysis of survival and prognostic features. Br J Haematol 1987 (65):23–29PubMedCrossRefGoogle Scholar
  538. 540.
    Richter MH: Generalised reticular sarcoma of lymph nodes associated with lymphatic leukemia. Am J Path 1928 (4):285–292PubMedGoogle Scholar
  539. 541.
    Lortholary P, Boiron M, Ripault P et al: Leucémie lymphoide chronique secondairment associée a une réticulopathie maligne; syndrome de Richter. Nouv Rev Fr Hematol 1964 (4):621–644Google Scholar
  540. 542.
    Van Dongen JJM, Hooijkaas H, Michels JJ et al: Richter’s syndrome with different immunoglobulin light chains and different heavy chain gene rearrangements. Blood 1984 (64):571–575PubMedGoogle Scholar
  541. 543.
    McDonnel JM, Beschomer WE, Staal SP et al: Richter’s syndrome with two different B-cell clones. Cancer 1986 (58):2031–2037CrossRefGoogle Scholar
  542. 544.
    Delsol G, Laurent G, Kuhlein E et al: Richter’s syndrome. Evidence for the clonal origin of the two proliferations. Am J Clin Path 1981 (76):308–315PubMedGoogle Scholar
  543. 545.
    Baumann MA, Libnoch JA, Patrick CW et al: Prolonged survival in Richter’s syndrome with subsequent reemergence of CLL. Am J Hematol 1985(20):67–72PubMedCrossRefGoogle Scholar
  544. 546.
    Harousseau JL, Flandrin G: Malignant lymphoma supervening in chronic lymphocytic leukemia and related disorders. Richter’s syndrome: a study of 25 cases. Cancer 1981 (48):1302–1308PubMedCrossRefGoogle Scholar
  545. 547.
    Galton DAG: Terminal transformation in B-cell chronic lymphocytic leukaemia. Bone Marrow Transpl 1989 (4 Suppl 1):156–157Google Scholar
  546. 548.
    Bouroncle BA, Wiseman BK and Doan CA: Leukaemic reticuloendotheliosis. Blood 1958 (13):609–630PubMedGoogle Scholar
  547. 549.
    Ewald O: Die Leukamische reticuloendotheliose. Deutsches Arch Klin Med 1923 (142):222–229Google Scholar
  548. 550.
    Rosenthal N and Lee SL: Reticulum cell leukaemia: A clinical and morphological entity. Report of 16 cases. Proc of 13th Annual Meeting of Am Soc Clin Path 1951Google Scholar
  549. 551.
    Belding HW, Dalard GA, Parker F: Histiocytic and monocytic leukemia. A clinical, hematological and pathological differentiation. Cancer 1955 (8):237–252PubMedCrossRefGoogle Scholar
  550. 552.
    Dameshek W: Proliferative disease of the reticuloendothelial system. II. Aleukemic reticulosis. Folia Haematol 1933 (49):64–67Google Scholar
  551. 553.
    Bouroncle BA: Leukemic reticuloendotheliosis (Hairy Cell Leukaemia). Blood 1979 (53):412–436PubMedGoogle Scholar
  552. 554.
    Flandrin G, Daniel MT, Fourcade M and Chelloul N: Leucemie a “Tricholeucocyte” (Hairy cell leukaemia): etude clinique et cytologique de 55 observations. Nouv Rev Fr Hematol 1973 (13):609–640PubMedGoogle Scholar
  553. 555.
    Schrek R, Donnelly WJ: “Hairy” cells in blood in lymphoreticular neoplastic disease and “flagellated” cells of normal lymph nodes. Blood 1966(27):199–211PubMedGoogle Scholar
  554. 556.
    Golomb HM, Catovsky D, Golde DW: Hairy cell leukaemia — A clinical review on 71 cases Ann Int Med 1978 (89):677–683PubMedGoogle Scholar
  555. 557.
    Cawley JC, Burns GF, Hayhoe FGJ: Hairy cell leukaemia. Recent Results in Cancer Research. Springer-Verlag, Berlin, Heidelberg 1980 (72)Google Scholar
  556. 558.
    Golomb HM and Hadad LJ: Infectious complications in 127 patients with hairy cell leukaemia. Am J Haematol 1984 (16):393–401CrossRefGoogle Scholar
  557. 559.
    Marie JP, Degos L and Flandrin G: Hairy cell leukemia and tuberculosis. N Engl J Med 1977 (297):1354 (letter)Google Scholar
  558. 560.
    Weinstein RA, Golomb HM, Grumet G et al: Hairy cell leukemia: association with disseminated atypical mycobacterial infection. Cancer 1981 (48):380–383PubMedCrossRefGoogle Scholar
  559. 561.
    Rice L, Shenkenberg T, Lynch EC et al: Granulomatous infections complicating hairy cell leukaemia. Cancer 1982 (49):1924–1928PubMedCrossRefGoogle Scholar
  560. 562.
    Elkon KB, Hughes GRV, Catovsky D et al: Hairy cell leukaemia with polyarteritis nodosa. Lancet 1979(2):280–282PubMedCrossRefGoogle Scholar
  561. 563.
    Raju SF, Chapman SW, Dreiling B et al: Hairy cell leukemia with the appearance of mixed cryoglobulinemia and vasculitis. Arch Int Med 1984 (144):1300–1302CrossRefGoogle Scholar
  562. 564.
    Dorsey JK and Penick GD: The association of hairy cell leukaemia with unusual immunologic disorders. Arch Int Med 1982 (142):902–903CrossRefGoogle Scholar
  563. 565.
    Le Pogamp P, Ghandour C and Le Prise PY: Hairy cell leukaemia and polyarteritis nodosa. J Rheumatol 1982 (9):441–442PubMedGoogle Scholar
  564. 566.
    Weh JH, Katz M, Bray B, Rodat O, Degos C and Flandrin G: Lesions ossueses au cours des leucemies a tricholeucocytes. Nouv Pres Med 1979 (8):2253–2254Google Scholar
  565. 567.
    Demanes DJ, Lane N and Beckstead JH: Bone involvement in hairy cell leukaemia. Cancer 1982 (49):1697–1701PubMedCrossRefGoogle Scholar
  566. 568.
    Embersky BC, Ratain MJ and Golomb HM: Skeletal complications in hairy cell leukaemia: Diagnosis and therapy. J Clin Oncol 1986 (6):1280–1284Google Scholar
  567. 569.
    Under J, Silberman HR and Croker BP: Amyloidosis complicating hairy cell leukemia Am Clin Path 1982 (78):864–867Google Scholar
  568. 570.
    Bouroncle BA: Unusual presentations and complications of hairy cell leukaemia. Leukemia 1987(1):288–293PubMedGoogle Scholar
  569. 571.
    Li CY, Yam LT and Lam KW: Studies of acid phosphatase isoenzymes in human leucocytes. Demonstration of isoenzyme cell specificity. J Histochem Cytochem 1970 (18):901–910PubMedCrossRefGoogle Scholar
  570. 572.
    Schwarting R, Stein H, Wang CY: Monoclonal antibodies SHCL-1 and SHCL-3 allow the diagnosis of hairy cell leukemia. Blood 1985 (65):974–983PubMedGoogle Scholar
  571. 573.
    Falini B, Palford K, Erber WN et al: Use of a panel of monoclonal antibodies for the diagnosis of hairy cell leukaemia. An immunocytochemical study of 36 cases. Histopathology 1986 (10):671–687574 Chilosi M and Pizzolo G: Immunophenotypical diagnosis and monitoring of hairy cell leukemia. Leukemia 1990 (4):168–169 (editorial)PubMedCrossRefGoogle Scholar
  572. 574.
    Chilosi M and Pizzolo G: Immunophenotypical diagnosis and monitoring of hairy cell leukemia. Leukemia 1990 (4):168–169 (editorial)PubMedGoogle Scholar
  573. 575.
    Thaler J, Dietze O, Faber V et al: Monoclonal antibody B-Ly7: A sensitive marker for detection of minimal residual disease in hairy cell leukemia. Leukemia 1990 (4):170–176PubMedGoogle Scholar
  574. 576.
    Rubin LA, Kurman CC, Fritz ME et al: Soluble interleukin-2 receptors are released from activated human lymphoid cells in vitro. J Immunol 1985 (135):3172–3177PubMedGoogle Scholar
  575. 577.
    Chilosi M, Semenzato G, Cetto G et al: Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity. Blood 1987(70):1530–1535PubMedGoogle Scholar
  576. 578.
    Pizzolo G, Chilosi, Semenzato G: The soluble interleukin-2 receptor in haematological disorders. Br J Haematol 1987 (67):377–380PubMedCrossRefGoogle Scholar
  577. 579.
    Semenzato G, Trentin L, Zambellow R et al: Origin of the soluble interleukin-2 receptor in the serum of patients with hairy cell leukemia. Leukemia 1988 (2):788–792PubMedGoogle Scholar
  578. 580.
    Ambrosetti A, Semenzato G, Prior M et al: Serum levels of soluble interleukin-2 receptors in hairy cell leukaemia: a reliable marker of neoplastic bulk. Br J Haematol 1989 (73):181–186PubMedCrossRefGoogle Scholar
  579. 581.
    Golomb HM: Progress report on chlorambucil therapy in post-splenectomy patients with progressive hairy cell leukemia. Blood 1981 (57):464–467PubMedGoogle Scholar
  580. 582.
    Jansen J and Hermans J: Clinical staging system for hairy cell leukaemia. Blood 1982 (60):571–577PubMedGoogle Scholar
  581. 583.
    Krigel R, Liebes LF, Pelle E and Silber R: Chlorambucil therapy in hairy cell leukemia: effects on lipid composition and lymphocyte subpopulations. Blood 1982 (60): 272–275PubMedGoogle Scholar
  582. 584.
    Porzsolt F, Raghavacher A, Digel W et al: Strategy for the treatment of hairy cell leukemia. Leukemia 1987(1):334–337PubMedGoogle Scholar
  583. 585.
    Quesada JR, Hersh EM and Gutterman JU: Therapy of hairy cell leukaemia with alpha interferon. Antiviral Research 1984 34: abstractGoogle Scholar
  584. 586.
    Quesada JR, Reuben J, Manning JT and Hersh EM: Alpha interferon for induction of remission in Hairy Cell Leukaemia. N Engl J Med 1984 (310):15–18PubMedCrossRefGoogle Scholar
  585. 587.
    Quesada JR, Lepe-Zuniga JL and Gutterman JV: Mid-term observations on the efficacy of alpha-interferon in hairy cell leukemia and status of the interferon system of patients in remission. Leukemia 1987 (1):317–319PubMedGoogle Scholar
  586. 588.
    Worman C, Catovsky D, Cawley JC et al: The UK experience with human lymphoblastic interferon in HCL: A report of the first 50 cases. Leukemia 1987 (1):320–322PubMedGoogle Scholar
  587. 589.
    Pralle H, Zwingers T, Boedewadt S et al: A prospective multicenter trial with human recombinant alpha 2C interferon in hairy cell leukemia before and after splenectomy. Leukemia 1987(1):337–340PubMedGoogle Scholar
  588. 590.
    Golomb HM and Ratain MJ: Recent advances in the treatment of hairy cell leukemia. N Engl J Med 1987 (316):870–871 (editorial)PubMedCrossRefGoogle Scholar
  589. 591.
    Samuels BL, Rosner MC, Giometti CS et al: Action of interferons in hairy cell leukemia. Leukemia 1987 (1):365–369PubMedGoogle Scholar
  590. 592.
    Cheson BD and Martin A: Clinical trials in hairy cell leukaemia. Ann Int Med 1987 (106):871–878PubMedGoogle Scholar
  591. 593.
    Figlin RA: Biotherapy in clinical practice. Semin Haematol 1989 (26 Suppl 3):15–24Google Scholar
  592. 594.
    Golomb HM, Ratain MJ, Fefer A, Johnson J et al: Randomised study of the duration of treatment with interferon alpha-2b in patients with hairy cell leukemia. JNCI 1988 (80):369–373PubMedGoogle Scholar
  593. 595.
    Golomb HM, Fefer A, Golde DW, Ozer H et al: Sequential evaluation of alpha-2b-interferon treatment in 128 patients with hairy cell leukaemia. Semin Oncol 1987 (14 Suppl 2):13–17PubMedGoogle Scholar
  594. 596.
    Ratain MJ, Golomb HM and Bardawil RG: Durability of responses to interferon alfa-2b in advanced hairy cell leukaemia. Blood 1987 (69):872–877PubMedGoogle Scholar
  595. 597.
    Thompson JA, Shields AF, Porter BA and Olsen DO: Magnetic resonance imaging of bone marrow in hairy cell leukaemia: Correlation with clinical response to alpha-interferon. Leukemia 1987 (1):315–316PubMedGoogle Scholar
  596. 598.
    Quesada JR, Talpaz M, Rios A, Kurzroch R and Gutterman JV: Clinical toxicity of interferons in cancer patients — a review. J Clin Oncol 1986 (4):234–243PubMedGoogle Scholar
  597. 599.
    Abrahams PG, McClamrock E and Foon KA: Evening administration of alpha interferon. N Engl J Med 1985 (312):443–444 (letter)CrossRefGoogle Scholar
  598. 600.
    Roth MS and Foon KA: Alpha Interferon in the treatment of hematologic malignancies. Am J Med 1986(81):871–882PubMedCrossRefGoogle Scholar
  599. 601.
    Roy V and Newland AC: Raynaud’s phenomenon and cryoglobulinaemia associated with the use of recombinant human alpha-interferon. Lancet 1988 (i): 944 (letter)CrossRefGoogle Scholar
  600. 602.
    Schilsky RL, Davidson HS, Magid D, Dalter S and Golomb HM: Gonadal and sexual functions in male patients with hairy cell leukaemia: lack of adverse effect of recombinant alpha interferon treatment. Cancer Treat Rep 1987 (71):179–181PubMedGoogle Scholar
  601. 603.
    Coci A, Costello A, Pagnucco G, et al: Bone marrow histology in patients with hairy cell leukaemia (HCL) treated by human lymphoblastoid interferon. Haematologica 1987 (72):143–148PubMedGoogle Scholar
  602. 604.
    Dupuy E, Sigaux F, Bryckaert MC et al: Platelet acquired defect in PDGF and beta haemoglobulin content in hairy cell leukaemia: improvement after interferon therapy. Br J Haematol 1987 (65):107–110PubMedCrossRefGoogle Scholar
  603. 605.
    Heslop HE, Bianchi AC, Cordingley FT et al: Mechanisms of action of alpha-interferon in B lymphoproliferative disorders. Nouv Pres Fr Med 1988(30):317–319Google Scholar
  604. 606.
    Cordingly FT, Bianchi A, Hoffbrand AV et al: Tumour necrosis factor as an autocrine tumour growth factor for chronic B- cell malignancies. Lancet 1988 (i): 969–971CrossRefGoogle Scholar
  605. 607.
    Bianchi AC, Heslop HE, Drexler HG et al: Effects of tumour necrosis factor and alpha interferon on chronic B-cell malignancies. Nouv Rev Fr Hematol 1988(30):317–319PubMedGoogle Scholar
  606. 608.
    Steis RG, Smith JW II, Urba W and Clark JW: Resistance to recombinant interferon alfa-2a in hairy cell leukemia associated with neutralizing anti-interferon antibodies. N Engl J Med 1988 (318):1409–1413PubMedCrossRefGoogle Scholar
  607. 609.
    Itri LM, Campion M, Dennin RA, Palleroni AV et al: Incidence and clinical significance of neutralizing antibodies in patients receiving recombinant interferon alfa-2a by intramuscular injection. Cancer 1987 (59 suppl 3):668–674PubMedCrossRefGoogle Scholar
  608. 610.
    Gauci L: Management of cancer patients receiving interferon alpha-2a. Int J Cancer 1987 (suppl 1):21–30CrossRefGoogle Scholar
  609. 611.
    Von Wussaw P, Freund M, Block B and Diedrich H: Clinical significance of anti-1FN-antibody titres during interferon therapy. Lancet 1987 (ii):635–636CrossRefGoogle Scholar
  610. 612.
    Spiegel RJ, Spicehandler JR, Jacobs SL and Oden EM: Low incidence of neutralizing factors in patients receiving recombinant alfa-2b interferon (INTRON). Am J Med 1986 (80): 223–228PubMedCrossRefGoogle Scholar
  611. 613.
    Moormeier JA, Westbrook CA, Ratain MJ and Golomb HM: Interferon Alfa-2b antibodies and clinical resistance in a patient with hairy cell leukaemia. Leuk Lymph 1989 (1):43–45CrossRefGoogle Scholar
  612. 614.
    Glaspy JA, Baldwin GC, Robertson BA and Olsen DO: Therapy of neutropenia in hairy cell leukaemia with recombinant human granulocytic colony-stimulating factor. Ann Int Med 1988 (109):789–795PubMedGoogle Scholar
  613. 615.
    Spiers ASD, Parekh SJ and Bishop MB: Hairy cell leukaemia: induction of complete remission with pentostatin (2’deoxycoformycin). J Clin Oncol 1984 (2):1336–1342PubMedGoogle Scholar
  614. 616.
    Spiers ASD, Moore D, Cassileth PA, Harrington DP et al: Remissions in hairy cell leukaemia with pentostatin (2’-deoxycoformycin). N Engl J Med 1987(316):825–830PubMedCrossRefGoogle Scholar
  615. 617.
    Kraut EH, Bouroncle BA and Grever MR: Low dose deoxycoformycin in the treatment of hairy cell leukaemia. Blood 1986 (68):1119–1122PubMedGoogle Scholar
  616. 618.
    Kraut EH, Bouroncle BA and Grever MR: Pentostatin in the treatment of advanced hairy cell leukaemia. J Clin Oncol 1989 (7):168–172PubMedGoogle Scholar
  617. 619.
    Murphy SB, Sinkule JA and Rivera G: Phase l-Il clincal and pharmacodynamic study of the effects of 2’- deoxycoformycin administered by continuous infusion in children with refractory acute lymphoblastic leukaemia. Cancer Treat Symp 1984 (2):55–61Google Scholar
  618. 620.
    Eisenhauer E, Johnston JB, Barr et al: 2’-deoxycoformycin (DCF) in hairy cell leukemia. In: Proceedings of the Fifth NCI/EORTC Symposium on New Drugs in Cancer Treatment. Free University Amsterdam, Netherlands 1986 Abstr No 1208Google Scholar
  619. 621.
    Ho A, Thaler J, Mandelli F et al: Response to Pentostatin in Hairy-Cell Leukemia refractory to interferon- alpha. J Clin Oncol 1989 (7):1533–1538PubMedGoogle Scholar
  620. 622.
    Smyth JF, Paine RM, Jackman AL, Harrap KR et al: The clinical pharmacology of the adenosine deminase inhibitor 2’deoxyco- formycin. Cancer Chemother Pharmacol 1980 (5):93–101PubMedCrossRefGoogle Scholar
  621. 623.
    Smyth JF and Harrap KR: Adenosine deaminase activity in leukaemia. Br J Cancer 1975 (31):544–549PubMedCrossRefGoogle Scholar
  622. 624.
    Smyth JF, Prentice HG, Proctor S and Hoffbrand AV: Deoxycoformycin in the treatment of leukaemias and lymphomas. Ann NY Acad Sci 1985 (451):123–128PubMedCrossRefGoogle Scholar
  623. 625.
    Grever MR, Sian ME, Jacob WF et al: The biochemical and clinical consequences of 2’deoxycoformycin in refractory lymphoproliferative malignancy. Blood 1981 (57):406–416PubMedGoogle Scholar
  624. 626.
    Seto S, Carvera CJ, Kubota M et al: Mechanism of deoxyadenosine and 2 chlorodeoxyadenosine toxicity to non-dividing human lymphocytes. J Clin Invest 1985 (75):377–383PubMedCrossRefGoogle Scholar
  625. 627.
    Kefford RF and Fox RM: Deoxycoformycin-induced response in chronic lymphatic leukaemia: Ω deoxyadenosine toxicity in non replicating lymphocytes. Br J Haematol 1982 (50): 627–636PubMedCrossRefGoogle Scholar
  626. 628.
    Lamballe F, Le Prise P-Y, Le Gall E and David JC: dATP-mediated inhibition of DNA Ligase by 2’-Deoxycoformycin in T and B cell Leukemia. Leukemia 1989 (3): 97–103PubMedGoogle Scholar
  627. 629.
    Urba WJ, Baseler MW, Kopp WC et al: Deoxycoformycin-induced immunosupression in patients with hairy cells. Blood 1989 (73): 38–46PubMedGoogle Scholar
  628. 630.
    Piro LO, Carrera CJ, Carson DA and Beutler E: Lasting remissions in hairy cell leukaemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med 1990 (322):1117–1121PubMedCrossRefGoogle Scholar
  629. 631.
    Kim IYZ, Lang CY, Cantoni GL et al: Inactivation of S-adenosylhomocy steine hydrolase by nucleosides. Biochem BioPhys Acta 1985 (829):150–155PubMedCrossRefGoogle Scholar
  630. 632.
    Golomb HM, Ratain MJ and Moormeier J: What is the choice of treatment for hairy cell leukemia J Clin Oncol 1989 (7):156–158 (editorial)PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • John Kempton Harold Rees
    • 1
  1. 1.Department of Haematology, Clinical Trials Unit, Addenbrooke’s HospitalUniversity of CambridgeCambridgeUK

Personalised recommendations