Skip to main content
SpringerLink
Log in

Proposal for the Classification of Relapsed and Refractory Acute Myeloid Leukemias as the Basis for an Age-Adjusted Randomized Comparison of Sequentially Applied High-Dose Versus Intermediate-Dose Cytosine Arabinoside in Combination with Mitoxantrone (S-HAM)

  • Conference paper
Acute Leukemias II

Part of the book series: Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ((HAEMATOLOGY,volume 33))

  • 154 Accesses

Abstract

In spite of the substantial improvement of first-line treatment in adult patients with acute myeloid leukemia (AML) and a grad-ual increase in long-term remissions, the majority of patients still relapse with their disease and ultimately die due to drug-resistant leukemia. More effective antileukemic therapy is therefore warranted and a variety of new drugs or new applications and dose ranges of established agents have been explored in clinical phase I and II studies. From these investigations cytosine arabinoside (Ara-C) obviously emerged as the most active single agent when administered at doses between 1.0 and 3.0 g/m2 over 4–6 days [1–7]. A more detailed analysis, however, reveals a substantial interstudy variation of response rates ranging from 11% to 70% even when considering only studies using the original Herzig regimen of 12 single doses of 3.0 g/m2 high-dose (HD) Ara-C [1–8].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Early AP, Preisler HD, Higby DJ, Brecher M, Browman G, McBride J A (1982) High-dose cytosine arabinoside. Clinical response to therapy in acute leukemia. Med Pediatr Oncol [Suppl 1]: 239

    Google Scholar 

  2. Willemze R, Zwaan FE, Colpin G, Keuning JJ (1982) High-dose cytosine arabinoside in the management of refractory acute leukaemia. Scand J Haematol 29: 141

    Article  PubMed  CAS  Google Scholar 

  3. Herzig RH, Wolff SN, Lazarus HM, Phillips GL, Karanes C, Herzig GP (1983) High-dose cytosine arabinoside therapy for refractory leukemia. Blood 62: 361

    PubMed  CAS  Google Scholar 

  4. Cantin G, Brennan JK (1984) High-dose cytosine arabinoside for acute nonlymphocytic leukemia. Am J Hematol 16: 59

    Article  PubMed  CAS  Google Scholar 

  5. Preisler HD, Epstein J, Barcos M, Priore R, Raza A, Browman GP, Vogler R, Winton E, Grunwald H, Rai K, Brennan J, Bennett J, Goldberg J, Gottlieb A, Chervenick P, Joyce R, Miller K, Larson R, D’Arrigo T, Doeblin T, Stein M, Bloom M, Steele R, Lee H (1984) Prediction of response of acute nonlymphocytic leukaemia to therapy with “high-dose” cytosine arabinoside. Br J Haematol 58: 19

    Article  PubMed  CAS  Google Scholar 

  6. Takaku F, Urabe A, Mizoguchi H, Yamada O, Wakabayashi Y, Miura Y, Sakamoto S, Yoshida M, Miwa S, Asano S, Morisaki T, Nomura T, Toyama K, Aoki I, Murase T, Maekawa T, Miyawaki S, Murakami H, Yamada H, Ohno R, Kawashima K, Yokomaku S, Kinugasa K, Adachi Y, Mori M, Ise T, Mutoh Y, Yamaguchi H (1985) High-dose cytosine arabinoside in the treatment of resistant acute leukemia. Semin Oncol 12 [Suppl 3]: 144

    PubMed  CAS  Google Scholar 

  7. Kantarjian HM, Estey EH, Plunkett W, Keating MJ, Walters RS, Iacoboni S, McCredie KB, Freireich EJ (1986) Phase I-II clinical and pharmacologic studies of high-dose cytosine arabinoside in refractory leukemia. Am J Med 81: 387

    Article  PubMed  CAS  Google Scholar 

  8. Vogler WR, Preisler HD, Winton EF, Gottlieb AJ, Goldberg J, Brennan J, Grunwald H, Rai K, Browman G, Miller KB, Chervenick P, Azarnia N (1986) Randomized trial of high-dose cytarabine versus amsacrine in acute myelogenous leukemia in relapse: a leukemia intergroup study. Cancer Treat Rep 70: 455

    PubMed  CAS  Google Scholar 

  9. Hiddemann W, Martin WR, Biichner T (1987) Definition of refractoriness to conventional therapy in advanced acute myeloid leukemia: an essential prerequisite for clinical phase I/II studies. Proc Am Assoc Cancer Res Am Soc Clin Oncol 6: 156

    Google Scholar 

  10. Keating MJ, Kantarjian H, Smith TL, Estey E, Walters R, Andersson B, Beran M, McCredie KB, Freireich EJ Response to salvage therapy and survival after relapse in acute myelogenous leukemia. J Clin Oncol (in press)

    Google Scholar 

  11. Biichner T, Urbanitz D, Hiddemann W, Riihl H, Ludwig WD, Fischer J, Aul HC, Vaupel HA, Kuse R, Zeile G, Nowrousian MR, Konig HJ, Walter M, Wendt FC, Sodomann H, Hossfeld DK, von Paleske A, Loffler H, Gassmann W, Hellriegel K-P, Fulle HH, Lunscken CH, Emmerich B, Pralle H, Pees HW, Pfreundschuh M, Bartels H, Koeppen K-M, Schwerdtfeger R, Donhuijsen-Ant R, Mainzer K, Bonfert B, Koppler H, Zurborn K-H, Ranft K, Thiel E, Heinecke A (1985) Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multi-center studies of the German AML Cooperative Group. J Clin Oncol 3: 1583

    Google Scholar 

  12. Buchner T, Hiddemann W, Koch P, Pielken H, Urbanitz D, Kreutzmann H, Maschmeyer G, Wendt F, Kuse R, Thiel E, Ludwig WD, Seibt H, Gassmann W, Loffler H, Aul C, Heyll A, Schneider W, Mertelsmann R, Anders CH, Nowrousian MR, Straif K, Hossfeld D, von Paleske A, Ho A, Fulle HH, Hellriegel K-P, Konig HJ, Emmerich B, Lengfelder E, Siegert W, Bartels H, Schwammborn J, Donhuijsen-Ant R, Vaupel HA, Konig E, Planker M, Middelhoff G, Mainzer K, Zurborn K-H, Koppler H, Nowicki L, Augener W, Karow J, Schroeder M, Eimermacher H, Sauerland MC, Heinecke A for the AML Cooperative Group. The role of maintenance chemotherapy, immunotherapy, induction dose reduction in elderly patients and double induction in the treatment of adult acute myeloid leukemia. Four randomized studies of the AML Cooperative Group. Blut (in press)

    Google Scholar 

  13. Hiddemann W, Aul C, Maschmeyer G, Lathan B, Koppler H, Hoffmann R, Griineisen T, Donhuijsen-Ant R, Ludwig WD, Balleisen L, Urbanitz D, Bettelheim P, Reichle A, Bartels H, Buchner T Age related randomized comparison of sequentially applied high-dose versus intermediate dose cytosine arabinoside in combination with mitoxantrone (S-HAM) in the treatment of relapsed and refractory acute myeloid leukemia: study design and preliminary results. Onkologie (in press)

    Google Scholar 

  14. Rees JKH, Swirsky D, Gray RG, Hayhoe FGJ (1986) Principal results of the Medical Research Councils’ 8th acute myeloid leukaemia trial. Lancet ii: 1236

    Google Scholar 

  15. Keating MJ, Estey E, Kantarjian H, Walters R, Smith T, McCredie KB, Freireich EJ (1987) Comparison of results of salvage therapy in adult acute myelogenous leukemia. Acta Haematol 78 [Suppl 1]: 120

    Article  PubMed  Google Scholar 

  16. Riva CM, Rustum YM, Preisler HD (1985) Pharmacokinetics and cellular determinants of response to l-β-arabinofuranosylcytosine (Ara-C). Semin Oncol 12 [Suppl 3]: 1

    PubMed  CAS  Google Scholar 

  17. Plunkett W, Lilienmark JO, Adams TM, Nowak B, Estey E, Kantarjian H, Keating MJ (1987) Saturation of 1-β-arabinofura-nosylcytosine 5’-triphosphate accumulation in leukemia cells during high-dose 1-β-D-arabinofuranosylcytosine therapy. Cancer Res 47: 3005

    PubMed  CAS  Google Scholar 

  18. Kessel D, Hall TC, Wodinsky I (1967) Transport and phosphorylation as factors in the antitumor action of cytosine arabinoside. Science 156: 1240

    Article  PubMed  CAS  Google Scholar 

  19. Chu MY, Fischer GA (1968) The incorporation of 3H-cytosine arabinoside and its effects on murine leukemia cells. Biochem Pharmacol 17: 753

    Article  PubMed  CAS  Google Scholar 

  20. Momparler RL, Chu MY, Fischer GA (1968) Studies on a new mechanism of resistance of L 5178 Y murine leukemia cells to cytosine arabinoside. Biochem Biophys Acta 161: 481

    PubMed  CAS  Google Scholar 

  21. Stewart CD, Burke PJ (1971) Cytidine deaminase and development of resistance to arabinosyl cytosine. Nature 223: 109

    Google Scholar 

  22. Tattersall MHN, Ganeshaguru K, Hoffbrand AV (1974) Mechanisms of resistance of human acute leukemia cells to cytosine arabinoside. Br J Haematol 27: 39

    Article  PubMed  CAS  Google Scholar 

  23. Abe I, Sato S, Honi K, Suzuki M, Sato H (1982) Role of dephosphorylation in accumulation of l-/?-D-arabinofuranosylcytosine 5’-triphosphate in human lymphoblastic cell lines with reference to their drug sensitivity. Cancer Res 42: 2846

    PubMed  CAS  Google Scholar 

  24. Willemze R, Fibbe WE, Zwaan FE (1983) Experience with intermediate and high-dose cytosine arabinoside in refractory acute leukemia. Onkologie 6: 200

    Article  PubMed  CAS  Google Scholar 

  25. Herzig RH, Hines JD, Herzig GP, Wolff SN, Cassileth PA, Lazarus HM, Adelstein DJ, Brown RA, Coccia PF, Strandjord S, Mazza JJ, Fay J, Phillips GL (1987) Cerebellar toxicity with high-dose cytosine arabinoside. J Clin Oncol 5: 927

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Internal Medicine, University of Münster, Germany

    W. Hiddemann & T. Büchner

  2. Departments of Internal Medicine, University of Düsseldorf, Germany

    H. C. Aul

  3. Departments of Internal Medicine, University of Ev. Krankenhaus Essen-Werden, Germany

    G. Maschmeyer

  4. Departments of Internal Medicine, University of St. Bernward Krankenhaus Hildesheim, Germany

    D. Urbanitz

  5. Departments of Internal Medicine, University of Köln, Germany

    B. Lathan

  6. Departments of Internal Medicine, University of München Innenstadt, Germany

    A. Reichle

  7. Departments of Internal Medicine, University of Marburg, Germany

    H. Köppler

  8. Departments of Internal Medicine, University of St.-Josefs-Hospital Duisburg-Hamborn, Germany

    R. Donhuijsen-Ant

  9. Departments of Internal Medicine, University of FU Berlin, Germany

    W. D. Ludwig

  10. Departments of Internal Medicine, University of Krankenhaus Berlin-Neukölln, Germany

    T. Grüneisen

  11. Departments of Internal Medicine, University of Wien, Austria

    P. Bettelheim

  12. Departments of Internal Medicine, University of Giessen, Germany

    W. Schroyens

  13. Departments of Internal Medicine, University of Ev. Krankenhaus Hamm, Germany

    L. Balleisen

  14. Departments of Internal Medicine, University of Städt. Krankenhaus Süd Lübeck, Germany

    H. Bartels

  15. Departments of Internal Medicine, University of Institut für Medizinische Dokumentation und Informatik Univ. Münster, Germany

    C. Sauerland & A. Heinecke

Authors
  1. W. Hiddemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. C. Aul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Maschmeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Urbanitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Lathan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Reichle
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H. Köppler
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. Donhuijsen-Ant
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. W. D. Ludwig
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T. Grüneisen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. P. Bettelheim
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. W. Schroyens
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. L. Balleisen
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. H. Bartels
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. C. Sauerland
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. A. Heinecke
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. T. Büchner
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Departments of Internal Medicine and Pediatrics, University of Münster, Albert-Schweitzer-Straße 33, D-4400, Münster, Federal Republic of Germany

    T. Büchner , G. Schellong , W. Hiddemann  & J. Ritter , ,  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Hiddemann, W. et al. (1990). Proposal for the Classification of Relapsed and Refractory Acute Myeloid Leukemias as the Basis for an Age-Adjusted Randomized Comparison of Sequentially Applied High-Dose Versus Intermediate-Dose Cytosine Arabinoside in Combination with Mitoxantrone (S-HAM). In: Büchner, T., Schellong, G., Hiddemann, W., Ritter, J. (eds) Acute Leukemias II. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 33. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74643-7_110

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-74643-7_110

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-50984-4

  • Online ISBN: 978-3-642-74643-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation