Therapy of diffuse aggressive lymphomas

  • Yener Koc
  • David P. Schenkein
Part of the Cancer Treatment and Research book series (CTAR, volume 99)


The non-Hodgkin’s lymphomas (NHLs) represent a heterogeneous group of disorders linked together by the commonality of a malignant monoclonal population of either B or T lymphocytes but differing in clinical presentation, prognosis, and treatment strategies. In 1997, the estimated number of new cases of NHL was 53,600, with a slight preponderance toward males (M/F ratio: 1.3)[1]. The estimated number of deaths secondary to NHL was 23,800 (44.4%) in the same year. Non-Hodgkin’s lymphoma is among the top 10 leading cancers in females and males, constituting 4% of newly diagnosed cancers in both sexes[1]. Among the reported deaths due to cancer in the United States, NHL is the second most frequent cause in males in the 15-34 age group and the third most frequent cause in the 35-54 age group[1]. The most common aggressive lymphoma is diffuse large B-cell lymphoma, accounting for 60%-70% of cases in the United States and Europe. The focus of this chapter will be the review of the treatment approaches for aggressive lymphomas as defined by both the Working Formulation (WF) and the Revised European-American Lymphoma (REAL) classification systems[2]. Treatment for the follicular lymphomas will be covered elsewhere.


Complete Remission Clin Oncol International Prognostic Index Anaplastic Large Cell Lymphoma Complete Remission Rate 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Parker S, Tong T, Bolden S, Wingo P. 1997. Cancer statistics, 1997. CA 47:5–27.PubMedGoogle Scholar
  2. 2.
    Harris N, Jaffe E, Stein H, et al. 1994. A revised European—American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84:1361–1392.PubMedGoogle Scholar
  3. 3.
    Shipp M, Harris N, Mauch P. 1997. The Non-Hodgkin’s lymphomas. J.B. Lippincott: Philadelphia.Google Scholar
  4. 4.
    Joensuu H, Ristamaki R, Soderstrom K, Jalkanen S. 1994. Effect of treatment on the prognostic value of S-phase fraction in non-Hodgkin’s lymphoma. J Clin Oncol 12:2167–2175.PubMedGoogle Scholar
  5. 5.
    Hill M, MacLennan K, Cunningham D, et al. 1996. Prognostic significance of BCL-2 expression and bcl-2 major breakpoint region rearrangement in diffuse large cell non-Hodgkin’s lymphoma: a British National Lymphoma Investigation Study. Blood 88:1046–1051.PubMedGoogle Scholar
  6. 6.
    Miller T, Grogan T, Dahlberg S, et al. 1994. Prognostic significance of the Ki-67-associated proliferative antigen in aggressive non-Hodgkin’s lymphomas: a prospective Southwest Oncology Group trial. Blood 83:1460–1466.PubMedGoogle Scholar
  7. 7.
    Ristamaki R, Joensuu H, Salmi M, Jalkanen S. 1994. Serum CD44 in malignant lymphoma: an association with treatment response. Blood 84:238–243.PubMedGoogle Scholar
  8. 8.
    Blay J, Burdin N, Rousset F, et al. 1993. Serum interleukin-10 in non-Hodgkin’s lymphoma: a prognostic factor. Blood 82:2169–2174.PubMedGoogle Scholar
  9. 9.
    Johnson P, Whelan J, Longhurst S, et al. 1993. Beta-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin’s lymphomas. Br J Cancer 67:792–797.PubMedGoogle Scholar
  10. 10.
    Seymour J, Talpaz M, Cabanillas F, Wetzler M, Kurzrock R. 1995. Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma. J Clin Oncol 13:575–582.PubMedGoogle Scholar
  11. 11.
    Stauder R, Eisterer W, Thaler J, Gunthert U. 1995. CD44 variant isoforms in non-Hodgkin’s lymphoma: a new independent prognostic factor. Blood 85:2885–2899.PubMedGoogle Scholar
  12. 12.
    Warzocha K, Salles G, Bienvenu J, et al. 1997. Tumor necrosis factor ligand-receptor system can predict treatment outcome in lymphoma patients. J Clin Oncol 15:499–508.PubMedGoogle Scholar
  13. 13.
    Anonymous. 1993. The International Non-Hodgkin’s Lymphoma Prognostic Factors Project: a predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 329:987–994.Google Scholar
  14. 14.
    Armitage J, Weisenburger D, Hutchins M, et al. 1986. Chemotherapy for diffuse large-cell lymphoma — rapidly responding patients have more durable remissions. J Clin Oncol 42: 160–164.Google Scholar
  15. 15.
    Kwak L, Halpern J, Olshen R, Horning S. 1990. Prognostic significance of actual dose intensity in diffuse large-cell lymphoma: results of a tree-structured survival analysis. J Clin Oncol 8:963–977.PubMedGoogle Scholar
  16. 16.
    Kaplan W, Jochelson M, Herman T, et al. 1990. Gallium-67 imaging: a predictor of residual tumor viability and clinical outcome in patients with diffuse large-cell lymphoma. J Clin Oncol 8:1966–1970.PubMedGoogle Scholar
  17. 17.
    Janicek M, Kaplan W, Neuberg D, Canellos G, Shulman L, Shipp M. 1997. Early restaging gallium scans predict outcome in poor-prognosis patients with aggressive non-Hodgkin’s lymphoma treated with high-dose CHOP chemotherapy. J Clin Oncol 15:1631–1637.PubMedGoogle Scholar
  18. 18.
    Grogan T, Lippman S, Spier C, et al. 1988. Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67. Blood 71:1157–1160.PubMedGoogle Scholar
  19. 19.
    Coiffier B, Brousse N, Peuchmaur M, et al. 1990. Peripheral T-cell lymphomas have a worse prognosis than B-cell lymphomas: a prospective study of 361 immunophenotyped patients treated with the LNH-84 regimen. The GELA (Groupe d’Etude des Lymphomes Agressives). Ann Oncol 1:45–50.PubMedGoogle Scholar
  20. 20.
    Miller T, Lippman S, Spier C, Slymen D, Grogan T. 1988. HLA-DR (Ia) immune phenotype predicts outcome for patients with diffuse large cell lymphoma. J Clin Invest 82:370–372.PubMedGoogle Scholar
  21. 21.
    Medeiros L, Picker L, Gelb A, et al. 1989. Numbers of host ‘helper’ T cells and proliferating cells predict survival in diffuse small-cell lymphomas. J Clin Oncol 7:1009–1017.PubMedGoogle Scholar
  22. 22.
    Swan FJ, Velasquez W, Tucker S, et al. 1989. A new serologic staging system for large-cell lymphomas based on initial beta 2-microglobulin and lactate dehydrogenase levels. J Clin Oncol 7:1518–1527.PubMedGoogle Scholar
  23. 23.
    Horst E, Meijer C, Radaszkiewicz T, Ossekoppele G, Van Krieken J, Pals S. 1990. Adhesion molecules in the prognosis of diffuse large-cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD54). Leukemia 4:595–599.PubMedGoogle Scholar
  24. 24.
    Cabanillas F, Pathak S, Grant G, et al. 1989. Refractoriness to chemotherapy and poor survival related to abnormalities of chromosomes 17 and 7 in lymphoma. Am J Med 87:167–172.PubMedGoogle Scholar
  25. 25.
    Hermine O, Haioun C, Lepage E, et al. 1996. Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin’s lymphoma. Groupe d’Etude des Lymphomes de l’Adulte (GELA). Blood 87:265–272.PubMedGoogle Scholar
  26. 26.
    De Vita VJ, Canellos G, Chabner B, Schein P, Hubbard S, Young R. 1975. Advanced diffuse histiocytic lymphoma, a potentially curable disease. Lancet 1:248–250.Google Scholar
  27. 27.
    Fisher R. 1994. Treatment of aggressive non-Hodgkin’ lymphomas. Lessons from the past 10 years. Cancer 74:2657–2661.PubMedGoogle Scholar
  28. 28.
    Fisher R, Gaynor E, Dahlberg S, et al. 1994. A phase III comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B in patients with intermediate-or high-grade non-Hodgkin’s lymphoma: results of SWOG-8516 (Intergroup 0067), the National High-Priority Lymphoma Study. Ann Oncol 5:91–95.PubMedGoogle Scholar
  29. 29.
    Kaminski M, Coleman C, Colby T, Cox R, Rosenberg S. 1986. Factors predicting survival in adults with stage I and II large-cell lymphoma treated with primary radiation therapy. Ann Intern Med 104:747–756.PubMedGoogle Scholar
  30. 30.
    Miller T, Jones S. 1983. Initial chemotherapy for clinically localized lymphomas of unfavorable histology. Blood 62:413–418.PubMedGoogle Scholar
  31. 31.
    Mauch P, Leonard R, Skarin A, et al. 1985. Improved survival following combined radiation therapy and chemotherapy for unfavorable prognosis stage I—II non-Hodgkin’s lymphomas. J Clin Oncol 3:1301–1308.PubMedGoogle Scholar
  32. 32.
    Glick J, Kim K, Earle J, O’Connell M. 1995. An ECOG randomized phase III trial of CHOP vs. CHOP + radiotherapy for intermediate grade early stage non-Hodgkin’s lymphoma. Proc Am Soc Clin Oncol 14:A1221.Google Scholar
  33. 33.
    Miller T, Dahlberg S, Cassady J, et al. 1996. Three cycles of CHOP plus radiotherapy is superior to eight cycles of CHOP alone for localized intermediate and high grade non-Hodgkin’s lymphoma: A Southwest Oncology Group Study. J Clin Oncol 15:A1257.Google Scholar
  34. 34.
    Longo D, Glatstein E, Duffey P, et al. 1989. Treatment of localized aggressive lymphomas with combination chemotherapy followed by involved-field radiation therapy. J Clin Oncol 7:1295–1302.PubMedGoogle Scholar
  35. 35.
    Connors J, Klimo P, Fairey R, Voss N. 1987. Brief chemotherapy and involved field radiation therapy for limited-stage, histologically aggressive lymphoma. Ann Intern Med 107:25–30.PubMedGoogle Scholar
  36. 36.
    Fisher R, Gaynor E, Dahlberg S, et al. 1993. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med 328:1002–1006.PubMedGoogle Scholar
  37. 37.
    Hryniuk W, Bush J. 1984. The importance of dose intensity in the chemotherapy of metastatic breast cancer. J Clin Oncol 2:1281–1288.PubMedGoogle Scholar
  38. 38.
    De Vita VJ, Hubbard S, Longo D. 1987. The chemotherapy of lymphomas: looking back, moving forward — the Richard and Hinda Rosenthal Foundation award lecture. Cancer Res 47:5810–5824.PubMedGoogle Scholar
  39. 39.
    Lepage E, Gisselbrecht C, Haioun C, et al. 1993. Prognostic significance of received relative dose intensity in non-Hodgkin’s lymphoma patients: application to LNH-87 protocol. The GELA (Groupe d’Etude des Lymphomes de l’Adulte). Ann Oncol 4:651–656.PubMedGoogle Scholar
  40. 40.
    Meyer R, Quirt I, Skillings J, et al. 1993. Escalated as compared with standard doses of doxorubicin in BACOP therapy for patients with non-Hodgkin’s lymphoma. N Engl J Med 329:1770–1776.PubMedGoogle Scholar
  41. 41.
    Pettengell R, Gurney H, Radford J, et al. 1992. Granulocyte colony-stimulating factor to prevent dose-limiting neutropenia in non-Hodgkin’s lymphoma: a randomized controlled trial. Blood 80:1430–1436.PubMedGoogle Scholar
  42. 42.
    Gerhartz H, Engelhard M, Meusers P, et al. 1993. Randomized, double-blind, placebo-controlled, phase III study of recombinant human granulocyte-macrophage colony-stimulating factor as adjunct to induction treatment of high-grade malignant non-Hodgkin’s lymphomas. Blood 82:2329–2339.PubMedGoogle Scholar
  43. 43.
    Shipp M, Neuberg D, Janicek M, Canellos G, Shulman L. 1995. High-dose CHOP as initial therapy for patients with poor-prognosis aggressive non-Hodgkin’s lymphoma: a dose-finding pilot study. J Clin Oncol 13:2916–2923.PubMedGoogle Scholar
  44. 44.
    Waits T, Greco F, Greer J, et al. 1993. Effective therapy for poor-prognosis non-Hodgkin’s lymphoma with 8 weeks of high-dose-intensity combination chemotherapy. J Clin Oncol 11:943–949.PubMedGoogle Scholar
  45. 45.
    Haioun C, Lepage E, Gisselbrecht C, et al. 1994. Comparison of Autologous Bone Marrow Transplantation with sequential chemotherapy for intermediate grade and high grade non-Hodgkin’s lymphoma in first complete remission: a study of 464 patients. J Clin Oncol 12: 2543–2551.PubMedGoogle Scholar
  46. 46.
    Reyes F, Lepage E, Morel P, et al. 1997. Failure of first line high-dose chemotherapy in poor risk patients with aggressive lymphoma: updated results of the randomized LNH93-3 study. Blood 90:594a.Google Scholar
  47. 47.
    Vitolo U, Cortellazzo S, Liberati A, et al. 1997. Intensified and high-dose chemotherapy with granulocyte colony-stimulating factor and autologous stem-cell transplantation support as first-line therapy in high-risk diffuse large-cell lymphoma. J Clin Oncol 15:491–498.PubMedGoogle Scholar
  48. 48.
    Stoppa A, Bouabdallah R, Chabannon C, et al. 1997. Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin’s lymphoma. J Clin Oncology 15:1722–1729.Google Scholar
  49. 49.
    Verdonck L, van Putten W, Hagenbeek A, et al. 1995. Comparison of CHOP chemotherapy with autologous bone marrow transplantation for slowly responding patients with aggressive non-Hodgkin’s lymphoma. N Engl J Med 332:1045–1051.PubMedGoogle Scholar
  50. 50.
    Martelli M, Vignetti M, Zinzani P, et al. 1996. High-dose chemotherapy followed by autologous bone marrow transplantation versus dexamethasone, cisplatin, and cytarabine in aggressive non-Hodgkin’s lymphoma with partial response to front-line chemotherapy: a prospective randomized Italian multicenter study. J Clin Oncol 14:534–542.PubMedGoogle Scholar
  51. 51.
    Gianni A, Bregni M, Siena S, et al. 1997. High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med 336:1290–1297.PubMedGoogle Scholar
  52. 52.
    Schenkein D, Roitman D, Miller K, et al. 1997. A phase II multicenter trial of high-dose sequential chemotherapy and peripheral blood stem cell transplantation as initial therapy for patients with high-risk non-Hodgkin’s lymphoma. Biol Blood Marrow Transplant 3:210–216.PubMedGoogle Scholar
  53. 53.
    Press O, Livingston R, Mortimer J, Collins C, Appelbaum F. 1991. Treatment of relapsed non-Hodgkin’s lymphomas with dexamethasone, high-dose cytarabine, and cisplatin before marrow transplantation. J Clin Oncol 9:423–431.PubMedGoogle Scholar
  54. 54.
    Velasquez W, Cabanillas F, Salvador P, et al. 1988. Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood 71: 117–122.PubMedGoogle Scholar
  55. 55.
    Velasquez W, McLaughlin P, Tucker S, et al. 1994. ESHAP — an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol 12: 1169–1176.PubMedGoogle Scholar
  56. 56.
    Chao N, Rosenberg S, Horning S. 1990. CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non-Hodgkin’s lymphoma. Blood 76:1293–1298.PubMedGoogle Scholar
  57. 57.
    Cabanillas F, Hagemeister F, Bodey G, Freireich E. 1982. IMVP-16: an effective regimen for patients with lymphoma who have relapsed after initial combination chemotherapy. Blood 60:693–697.PubMedGoogle Scholar
  58. 58.
    Engert A, Schnell R, Kupper F, et al. 1997. A phase-II study with idarubicin, ifosfamide and VP-16 (IIVP-16) in patients with refractory or relapsed aggressive and high grade non-Hodgkin’s lymphoma. Leuk Lymphoma 24:513–522.PubMedGoogle Scholar
  59. 59.
    Wilson W, Bryant G, Bates S, et al. 1993. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin’s lymphoma. J Clin Oncol 11:1573–1582.PubMedGoogle Scholar
  60. 60.
    Sparano J, Wiernik P, Leaf A, Dutcher J. 1993. Infusional cyclophosphamide, doxorubicin, and etoposide in relapsed and resistant non-Hodgkin’s lymphoma: evidence for a schedule-dependent effect favoring infusional administration of chemotherapy. J Clin Oncol 11:1071–1079.PubMedGoogle Scholar
  61. 61.
    Bosly A, Coiffier B, Gisselbrecht C, et al. 1992. Bone marrow transplantation prolongs survival after relapse in aggressive-lymphoma patients treated with the LNH-84 regimen. J Clin Oncol 10:1615–1623.PubMedGoogle Scholar
  62. 62.
    Takvorian T, Canellos G, Ritz J, et al. 1987. Prolonged disease-free survival after autologous bone marrow transplantation in patients with non-Hodgkin’s lymphoma with a poor prognosis. N Engl J Med 316:1499–1505.PubMedGoogle Scholar
  63. 63.
    Philip T, Armitage J, Spitzer G, et al. 1987. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin’s lymphoma. N Engl J Med 316:1493–1498.PubMedGoogle Scholar
  64. 64.
    Philip T, Hartmann O, Biron P, et al. 1988. High-dose therapy and autologous bone marrow transplantation in partial remission after first-line induction therapy for diffuse non-Hodgkin’s lymphoma. J Clin Oncol 6:1118–1124.PubMedGoogle Scholar
  65. 65.
    Gribben J, Goldstone A, Linch D, et al. 1989. Effectiveness of high-dose combination chemotherapy and autologous bone marrow transplantation for patients with non-Hodgkin’s lymphomas who are still responsive to conventional-dose therapy. J Clin Oncol 7:1621–1629.PubMedGoogle Scholar
  66. 66.
    Freedman A, Takvorian T, Anderson K, et al. 1990. Autologous bone marrow transplantation in B-cell non-Hodgkin’s lymphoma: very low treatment-related mortality in 100 patients in sensitive relapse. J Clin Oncol 8:784–791.PubMedGoogle Scholar
  67. 67.
    Weaver C, Petersen F, Appelbaum F, et al. 1994. High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma. J Clin Oncol 12:2559–2566.PubMedGoogle Scholar
  68. 68.
    Horning S, Negrin R, Chao J, Long G, Hoppe R, Blume K. 1994. Fractionated total-body irradiation, etoposide, and cyclophosphamide plus autografting in Hodgkin’s disease and non-Hodgkin’s lymphoma. J Clin Oncol 12:2552–2558.PubMedGoogle Scholar
  69. 69.
    Philip T, Guglielmi C, Hagenbeek A, et al. 1995. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med 333:1540–1545.PubMedGoogle Scholar
  70. 70.
    McCann J, Kanteti R, Shilepsky B, Miller K, Sweet M, Schenkein D. 1996. High degree of occult tumor contamination in bone marrow and peripheral blood stem cells of patients undergoing autologous transplantation for non-Hodgkin’s lymphoma. Biol Blood Marrow Transplant 2:37–43.PubMedGoogle Scholar
  71. 71.
    Hoskins P, Ng V, Spinelli J, Klimo P, Connors J. 1991. Prognostic variables in patients with diffuse large-cell lymphoma treated with MACOP-B. J Clin Oncol 9:220–226.PubMedGoogle Scholar
  72. 72.
    d’Amore F, Brincker H, Christensen B, et al. 1992. Non-Hodgkin’s lymphoma in the elderly. A study of 602 patients aged 70 or older from a Danish population-based registry. The Danish LYEO-Study Group. Ann Oncol 3:379–386.PubMedGoogle Scholar
  73. 73.
    Vose J, Armitage J, Weisenburger D, et al. 1988. The importance of age in survival of patients treated with chemotherapy for aggressive non-Hodgkin’s lymphoma. J Clin Oncol 6:1838–1844.PubMedGoogle Scholar
  74. 74.
    Epelbaum R, Haim N, Leviov M, Ben-Shahar M, Ben-Arie Y, Dror Y. 1995. Full dose CHOP chemotherapy in elderly patients with non-Hodgkin’s lymphoma. Acta Oncol 34:87–91.PubMedGoogle Scholar
  75. 75.
    Meyer R, Browman G, Samosh M, et al. 1995. Randomized phase II comparison of standard CHOP with weekly CHOP in elderly patients with non-Hodgkin’s lymphoma. J Clin Oncol 13:2386–2393.PubMedGoogle Scholar
  76. 76.
    Gaynor E, Dahlberg S, Fisher R. 1994. Factors affecting reduced survival of the elderly with intermediate and high grade lymphoma: an analysis of SWOG-8516 (INT 0067) The National High Priority Lymphoma Study — a randomized comparison of CHOP vs. m-BACOD vs. ProMACE-CytaBOM vs. MACOP-B. Proc Am Soc Clin Oncol 13: 1250a.Google Scholar
  77. 77.
    Tirelli U, Errante D, Glaggeke M, et al. 1998. CHOP is the standard regimen in patients ≥70 years of age with intermediate-grade and high-grade non-Hodgkin’s lymphoma: Results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group. J Clin Oncol 16:27–34.PubMedGoogle Scholar
  78. 78.
    Coiffier B. 1994. What treatment for elderly patients with aggressive lymphoma? Ann Oncol 5:873–875.PubMedGoogle Scholar
  79. 79.
    Sonneveld P, de Ridder M, van der Lelie H, et al. 1995. Comparison of doxorubicin and mitoxantrone in the treatment of elderly patients with advanced diffuse non-Hodgkin’s lymphoma using CHOP versus CNOP chemotherapy. J Clin Oncol 13:2530–2539.PubMedGoogle Scholar
  80. 80.
    Bertini M, Freilone R, Vitolo U, et al. 1994. P-VEBEC: a new 8-weekly schedule with or without rG-CSF for elderly patients with aggressive non-Hodgkin’s lymphoma (NHL). Ann Oncol 5:895–900.PubMedGoogle Scholar
  81. 81.
    McMaster M, Greer J, Greco F, Johnson D, Wolff S, Hainsworth J. 1991. Effective treatment of small-noncleaved-cell lymphoma with high-intensity, brief-duration chemotherapy. J Clin Oncol 9:941–946.PubMedGoogle Scholar
  82. 82.
    Martelli M, Guglielmi C, Coluzzi S, et al. 1993. P-VABEC: a prospective study of a new weekly chemotherapy regimen for elderly aggressive non-Hodgkin’s lymphoma. J Clin Oncol 11:2362–2369.PubMedGoogle Scholar
  83. 83.
    Tirelli U, Zagonel V, Errante D, et al. 1992. A prospective study of a new combination chemotherapy regimen in patients older than 70 years with unfavorable non-Hodgkin’s lymphoma. J Clin Oncol 10:228–236.PubMedGoogle Scholar
  84. 84.
    O’Reilly S, Klimo P, Connors J. 1991. Low-dose ACOP-B and VABE. weekly chemotherapy for elderly patients with advanced-stage diffuse large-cell lymphoma. J Clin Oncol 9:741–747.PubMedGoogle Scholar
  85. 85.
    O’Reilly S, Connors J, Howdle S, et al. 1993. In search of an optimal regimen for elderly patients with advanced-stage diffuse large-cell lymphoma: results of a phase II study of P/ DOCE chemotherapy. J Clin Oncol 11:2250–2257.PubMedGoogle Scholar
  86. 86.
    Armitage J. 1997. A clinical evaluation of the international lymphoma study group classification of non-Hodgkin’s lymphoma. Blood 89:3909–3918.Google Scholar
  87. 87.
    Levine A, Pavlova Z, Pockros A, et al. 1983. Small noncleaved follicular center cell (FCC) lymphoma: Burkitt and non-Burkitt variants in the United States. I. Clinical features. Cancer 52:1073–1079.PubMedGoogle Scholar
  88. 88.
    Yano T, van Krieken J, Magrath I, Longo D, Jaffe E, Raffeid M. 1992. Histogenetic correlations between subcategories of small noncleaved cell lymphomas. Blood 79:1282–1290.PubMedGoogle Scholar
  89. 89.
    Magrath I, Shiramizu B. 1989. Biology and treatment of small non-cleaved cell lymphoma. Oncology 3:41–53.PubMedGoogle Scholar
  90. 90.
    Croce C. 1993. Molecular biology of lymphomas. Semin Oncol 20:31–46.PubMedGoogle Scholar
  91. 91.
    Murphy S, Bowman W, Abromowitch M, et al. 1986. Results of treatment of advanced-stage Burkitt’s lymphoma and B cell (SIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and coordinated high-dose methotrexate and cytarabine. J Clin Oncol 4:1732–1739.PubMedGoogle Scholar
  92. 92.
    Straus D, Wong G, Liu J, et al. 1991. Small non-cleaved-cell lymphoma (undifferentiated lymphoma, Burkitt’s type) in American adults: results with treatment designed for acute lymphoblastic leukemia. Am J Med 90:328–337.PubMedGoogle Scholar
  93. 93.
    Schwenn M, Blattner S, Lynch E, Weinstein H. 1991. HiC-COM: a 2-month intensive chemotherapy regimen for children with stage III and IV Burkitt’s lymphoma and B-cell acute lymphoblastic leukemia. J Clin Oncol 9:133–138.PubMedGoogle Scholar
  94. 94.
    Lopez T, Hagemeister F, McLaughlin P, et al. 1990. Small noncleaved cell lymphoma in adults: superior results for stages I–III disease. J Clin Oncol 8:615–622.PubMedGoogle Scholar
  95. 95.
    McMaster M, Johnson D, Greer J, et al. 1991. A brief-duration combination chemotherapy for elderly patients with poor-prognosis non-Hodgkin’s lymphoma. Cancer 67:1487–1492.PubMedGoogle Scholar
  96. 96.
    Soussain C, Patte C, Ostronoff M, et al. 1995. Small noncleaved cell lymphoma and leukemia in adults. A retrospective study of 65 adults treated with the LMB pediatric protocols. Blood 85:664–674.PubMedGoogle Scholar
  97. 97.
    Troussard X, Leblond V, Kuentz M, et al. 1990. Allogeneic bone marrow transplantation in adults with Burkitt’s lymphoma or acute lymphoblastic leukemia in first complete remission. J Clin Oncol 8:809–812.PubMedGoogle Scholar
  98. 98.
    Nathwani B, Kim H, Rappaport H. 1976. Malignant lymphoma, lymphoblastic. Cancer 38:964–983.PubMedGoogle Scholar
  99. 99.
    Foon K, Todd R. 1986. Immunologic classification of leukemia and lymphoma. Blood 68:1–31.PubMedGoogle Scholar
  100. 100.
    Weiss L, Bindl J, Picozzi V, Link M, Warnke R. 1986. Lymphoblastic lymphoma: an immunophenotype study of 26 cases with comparison to T cell acute lymphoblastic leukemia. Blood 67:474–478.PubMedGoogle Scholar
  101. 101.
    Picozzi VJ, Coleman C. 1990. Lymphoblastic lymphoma. Semin Oncol 17:96–103.PubMedGoogle Scholar
  102. 102.
    Anonymous. 1982. National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphomas: summary and description of a working formulation or clinical usage. The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Cancer 49:2112–2135.Google Scholar
  103. 103.
    Coleman C, Picozzi VJ, Cox R, et al. 1986. Treatment of lymphoblastic lymphoma in adults. J Clin Oncol 4:1628–1637.PubMedGoogle Scholar
  104. 104.
    Coleman C, Cohen J, Burke J, Rosenberg S. 1981. Lymphoblastic lymphoma in adults: results of a pilot protocol. Blood 57:679–684.PubMedGoogle Scholar
  105. 105.
    Levine A, Forman S, Meyer P, et al. 1983. Successful therapy of convoluted T-lymphoblastic lymphoma in the adult. Blood 61:92–98.PubMedGoogle Scholar
  106. 106.
    Slater D, Mertelsmann R, Koziner B, et al. 1986. Lymphoblastic lymphoma in adults. J Clin Oncol 4:57–67.PubMedGoogle Scholar
  107. 107.
    Colgan J, Andersen J, Habermann T, et al. 1994. Long-term follow-up of a CHOP-based regimen with maintenance therapy and central nervous system prophylaxis in lymphoblastic non-Hodgkin’s lymphoma. Leuk Lymphoma 15:291–296.PubMedGoogle Scholar
  108. 108.
    Morel P, Lepage E, Brice P, et al. 1992. Prognosis and treatment of lymphoblastic lymphoma in adults: a report on 80 patients. J Clin Oncol 10:1078–1085.PubMedGoogle Scholar
  109. 109.
    Zinzani P, Bendandi M, Visani G, et al. 1996. Adult lymphoblastic lymphoma: clinical features and prognostic factors in 53 patients. Leuk Lymphoma 23:577–582.PubMedGoogle Scholar
  110. 110.
    Willemze R, Zijlmans J, den Ottolander G, et al. 1995. High-dose Ara-C for remission induction and consolidation of previously untreated adults with ALL or lymphoblastic lymphoma. Ann Hematol 70:71–74.PubMedGoogle Scholar
  111. 111.
    Santini G, Congiu A, Coser P, et al. 1991. Autologous bone marrow transplantation for adult advanced stage lymphoblastic lymphoma in first CR. A study of the NHLCSG. Leukemia 5:42–45.PubMedGoogle Scholar
  112. 112.
    Verdonck L, Dekker A, de Gast G, Lokhorst H, Nieuwenhuis H. 1992. Autologous bone marrow transplantation for adult poor-risk lymphoblastic lymphoma in first remission. J Clin Oncol 10:644–646.PubMedGoogle Scholar
  113. 113.
    Sweetenham J, Liberti G, Pearce R, Taghipour G, Santini G, Goldstone A. 1994. High-dose therapy and autologous bone marrow transplantation for adult patients with lymphoblastic lymphoma: results of the European Group for Bone Marrow Transplantation. J Clin Oncol 12:1358–1365.PubMedGoogle Scholar
  114. 114.
    De Witte T, Awwad B, Boezeman J, et al. 1994. Role of allogenic bone marrow transplantation in adolescent or adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma in first remission. Bone Marrow Transplant 14:767–774.PubMedGoogle Scholar
  115. 115.
    Pileri S, Bocchia M, Baroni C, et al. 1994. Anaplastic large cell lymphoma (CD30 +/Ki-1+): results of a prospective clinico-pathological study of 69 cases. Br J Haematol 86:513–523.PubMedGoogle Scholar
  116. 116.
    Yee H, Ponzoni M, Merson A, et al. 1996. Molecular characterization of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin’s disease. Blood 87: 1081–1088.PubMedGoogle Scholar
  117. 117.
    Lamant L, Meggetto F, al Saati T, et al. 1996. High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin’s disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining. Blood 87:284–291.PubMedGoogle Scholar
  118. 118.
    Elmberger P, Lozano M, Weisenburger D, Sanger W, Chan W. 1995. Transcripts of the npmalk fusion gene in anaplastic large cell lymphoma, Hodgkin’s disease, and reactive lymphoid lesions. Blood 86:3517–3521.PubMedGoogle Scholar
  119. 119.
    Gause A, Jung W, Schmits R, et al. 1992. Soluble CD8, CD25 and CD30 antigens as prognostic markers in patients with untreated Hodgkin’s lymphoma. Ann Oncol 3:49–52.PubMedGoogle Scholar
  120. 120.
    Nadali G, Vinante F, Stein H, et al. 1995. Serum levels of the soluble form of CD30 molecule as a tumor marker in CD30+ anaplastic large-cell lymphoma. J Clin Oncol 13:1355–1360.PubMedGoogle Scholar
  121. 121.
    Paulli M, Berti E, Rosso R, et al. 1995. CD30/Ki-1-positive lymphoproliferative disorders of the skin — clinicopathologic correlation and statistical analysis of 86 cases: a multicentric study from the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group. J Clin Oncol 13:1343–1354.PubMedGoogle Scholar
  122. 122.
    Zinzani P, Bendandi M, Martelli M, et al. 1996. Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients. J Clin Oncol 14:955–962.PubMedGoogle Scholar
  123. 123.
    Nakamura S, Takagi N, Kojima M, et al. 1991. Clinicopathologic study of large cell anaplastic lymphoma (Ki-1-positive large cell lymphoma) among the Japanese. Cancer 68:118–129.PubMedGoogle Scholar
  124. 124.
    Greer J, Kinney M, Collins R, et al. 1991. Clinical features of 31 patients with Ki-1 anaplastic large-cell lymphoma. J Clin Oncol 9:539–547.PubMedGoogle Scholar
  125. 125.
    Tilly H, Gaulard P, Lepage E, et al. 1997. Primary anaplastic large-cell lymphoma in adults: clinical presentation, immunophenotype, and outcome. Blood 90:3727–3734.PubMedGoogle Scholar
  126. 126.
    Fisher R. 1997. Cyclophosphamide, doxorubicin, vincristine, and prednisone versus intensive chemotherapy in non-Hodgkin’s lymphoma. Cancer Chemother Pharmacol 40:S42–S46.PubMedGoogle Scholar
  127. 127.
    Grogan T, Miller T, Dahlberg S, et al. 1996. REAL classification of lymphoma allows improved delineation of histologic risk groups: a Southwest Oncology Group study. Proc Annu Meet Am Soc Clin Oncol 15:A1310.Google Scholar
  128. 128.
    Shiota M, Nakamura S, Ichinohasama R, et al. 1995. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity. Blood 86:1954–1960.PubMedGoogle Scholar
  129. 129.
    Shiota M, Mori S. 1997. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity. Leukemia 11:538–540.PubMedGoogle Scholar
  130. 130.
    Fanin R, Silvestri F, Geromin A, et al. 1997. Sequential intensive treatment with the F-MACHOP regimen (+/-radiotherapy) and autologous stem cell transplantation for primary systemic CD30 (Ki-1) — positive anaplastic large cell lymphoma in adults. Leuk Lymphoma 24:369–377.PubMedGoogle Scholar
  131. 131.
    Fanin R, Silvestri F, Geromin A, et al. 1996. Primary systemic CD30 (Ki-1)-positive anaplastic large cell lymphoma of the adult: sequential intensive treatment with the F-MACHOP regimen (+/-radiotherapy) and autologous bone marrow transplantation. Blood 87:1243–1248.PubMedGoogle Scholar
  132. 132.
    Cheng A, Chen Y, Wang C, et al. 1989. Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades — should peripheral T-cell lymphoma be considered separately? J Clin Oncol 7:725–731.PubMedGoogle Scholar
  133. 133.
    Coiffier B, Berger F, Bryon P, Magaud J. 1988. T-cell lymphomas: immunologic, histologic, clinical, and therapeutic analysis of 63 cases. J Clin Oncol 6:1584–1589.PubMedGoogle Scholar
  134. 134.
    Armitage J, Greer J, Levine A, et al. 1989. Peripheral T-cell lymphoma. Cancer 63:158–163.PubMedGoogle Scholar
  135. 135.
    Ascani S, Zinzani P, Gherlinzoni F, et al. 1997. Peripheral T-cell lymphomas. Clinicopathologic study of 168 cases diagnosed according to the R.E.A.L. Classification. Ann Oncol 8:583–592.Google Scholar
  136. 136.
    Zaja F, Russo D, Silvestri F, et al. 1997. Retrospective analysis of 23 cases with peripheral T-cell lymphoma, unspecified: clinical characteristics and outcome. Haematologica 82:171–177.PubMedGoogle Scholar
  137. 137.
    Su I, Cheng A, Tsai T, Lay J. 1993. Retinoic acid-induced apoptosis and regression of a refractory Epstein—Barr virus-containing T cell lymphoma expressing multidrug-resistance phenotypes. Br J Haematol 85:826–828.PubMedGoogle Scholar
  138. 138.
    Bonnefoix T, Gressin R, Jacrot M, et al. 1997. Growth modulation of freshly isolated non-Hodgkin’s B-lymphoma cells induced by various cytokines and all-trans-retinoic-acid. Leuk Lymphoma 25:169–178.PubMedGoogle Scholar
  139. 139.
    Chan L, Zhang S, Shao J, Waikel R, Thompson E, Chan T. 1997. N-(4-hydroxyphenyl)retinamide induces apoptosis in T lymphoma and T lymphoblastoid leukemia cells. Leuk Lymphoma 25:271–280.PubMedGoogle Scholar
  140. 140.
    Dreno B, Celerier P, Litoux P. 1993. Roferon-A in combination with Tigason in cutaneous T-cell lymphomas. Acta Haematol 89:28–32.PubMedGoogle Scholar
  141. 141.
    Cheng A, Su I, Chen C, et al. 1994. Use of retinoic acids in the treatment of peripheral T-cell lymphoma: a pilot study. J Clin Oncol 12:1185–1192.PubMedGoogle Scholar
  142. 142.
    Chou W, Su I, Tien H, et al. 1996. Clinicopathologic, cytogenetic, and molecular studies of 13 Chinese patients with Ki-1 anaplastic large cell lymphoma. Special emphasis on the tumor response to 13-cis retinoic acid. Cancer 78:1805–1812.PubMedGoogle Scholar
  143. 143.
    Dyer M, Hale G, Hayhoe F, Waldmann H. 1989. Effects of CAMPATH-1 antibodies in vivo in patients with lymphoid malignancies: influence of antibody isotype. Blood 73:1431–1439.PubMedGoogle Scholar
  144. 144.
    Press O, Appelbaum F, Ledbetter J, et al. 1987. Monoclonal antibody 1F5 (anti-CD20) serotherapy of human B cell lymphomas. Blood 69:584–591.PubMedGoogle Scholar
  145. 145.
    Maloney D, Grillo-Lopez A, White C, et al. 1997. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin’s lymphoma. Blood 90:2188–2195.PubMedGoogle Scholar
  146. 146.
    Corcoran M, Eary J, Bernstein I, Press O. 1997. Radioimmunotherapy strategies for non-Hodgkin’s lymphomas. Ann Oncol 8:133–138.PubMedGoogle Scholar
  147. 147.
    Press O, Eary J, Badger C, et al. 1989. Treatment of refractory non-Hodgkin’s lymphoma with radiolabeled MB-1 (anti-CD37) antibody. J Clin Oncol 7:1027–1038.PubMedGoogle Scholar
  148. 148.
    Kaminski M, Zasadny K, Francis I, et al. 1996. Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma. J Clin Oncol 14:1974–1981.PubMedGoogle Scholar
  149. 149.
    Matthews D, Appelbaum F, Press O, Eary J, Bernstein I. 1997. The use of radiolabeled antibodies in bone marrow transplantation for hematologic malignancies. Cancer Treat Res 77:121–139.PubMedGoogle Scholar
  150. 150.
    Press O, Eary J, Appelbaum F, et al. 1995. Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet 346:336–340.PubMedGoogle Scholar
  151. 151.
    Pasqualucci L, Wasik M, Teicher B, et al. 1995. Antitumor activity of anti-CD30 immunotoxin (Ber-H2/saporin) in vitro and in severe combined immunodeficiency disease mice xenografted with human CD30+ anaplastic large-cell lymphoma. Blood 85:2139–2146.PubMedGoogle Scholar
  152. 152.
    Flavell D, Boehm D, Emery L, Noss A, Ramsay A, Flavell S. 1995. Therapy of human B-cell lymphoma bearing SCID mice is more effective with anti-CD 19-and anti-CD38-saporin immunotoxins used in combination than with either immunotoxin used alone. Int J Cancer 62:337–344.PubMedGoogle Scholar
  153. 153.
    LeMaistre C, Saleh M, Kuzel T, et al. 1988. Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for Interleukin-2. Blood 91:399–405.Google Scholar
  154. 154.
    Scadden D, Diweiko J, Schenkein D, Bernstein Z, Levine A. 1993. A Phase I/II trial of combined immunoconjugate and chemotherapy for AIDS-related lymphoma. Blood 82:386a.Google Scholar
  155. 155.
    Grossbard M, Lambert J, Goldmacher V, et al. 1993. Anti-B4-blocked ricin: a phase I trial of 7-day continuous infusion in patients with B-cell neoplasms. J Clin Oncol 11:726–737.PubMedGoogle Scholar
  156. 156.
    Grossbard M, Gribben J, Freedman A, et al. 1993. Adjuvant immunotoxin therapy with anti-B4-blocked ricin after autologous bone marrow transplantation for patients with B-cell non-Hodgkin’s lymphoma. Blood 81:2263–2271.PubMedGoogle Scholar
  157. 157.
    Nelson E, Li X, Hsu F, et al. 1996. Tumor-specific, cytotoxic T-lymphocyte response after idiotype vaccination for B-cell, non-Hodgkin’s lymphoma. Blood 88:580–589.PubMedGoogle Scholar
  158. 158.
    Hsu F, Benike C, Fagnoni F, et al. 1996. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 2:52–58.PubMedGoogle Scholar
  159. 159.
    George A, Stevenson F. 1989. Prospects for the treatment of B cell tumors using idiotypic vaccination. Int Rev Immunol 4:271–310.PubMedGoogle Scholar
  160. 160.
    Smith C, Ng C, Loftin S, et al. 1996. Adoptive immunotherapy for Epstein—Barr virus-related lymphoma. Leuk Lymphoma 23:213–220.PubMedGoogle Scholar
  161. 161.
    Ueda M, Joshi I, Dan M, et al. 1993. Preclinical studies for adoptive immunotherapy in bone marrow transplantation. Generation of anti-CD3 activated cytotoxic T cells from normal donors and autologous bone marrow transplant candidates. Transplantation 56:351–356.PubMedGoogle Scholar
  162. 162.
    O’Reilly R, Lacerda J, Lucas K, Rosenfield N, Small T, Papadopoulos E. 1996. Adoptive cell therapy with donor lymphocytes for EBV-associated lymphomas developing after allogeneic marrow transplants. Important Adv Oncol 11:149–166.Google Scholar
  163. 163.
    Haioun C, Lepage E, Gisselbrecht C, et al. 1997. Benefit of autologous bone marrow transplantation over sequential chemotherapy in poor-risk aggressive non-Hodgkin’s lymphoma: updated results of the prospective study LNH87-2. Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol 15:1131–1137.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1999

Authors and Affiliations

  • Yener Koc
  • David P. Schenkein

There are no affiliations available

Personalised recommendations