Skip to main content

Stratification of Postremission Therapy in Adult Acute Myeloid Leukemia According to the Karyotype — Preliminary Results of the Multicenter Treatment Trial AML HD93

  • Conference paper
Acute Leukemias VII

Abstract

Specific chromosome aberrations are one of the most important predictive factors for response rate and remission duration in acute myeloid leukemia (AML). In June 1993, we initiated a multicenter treatment trial for adult AML (AML HD93) in which the karyotype is used for stratifying postremission therapy. The patients, except those with acute promyelocytic leukemia, receive an intensive double induction chemotherapy consisting of 2 cycles of idarubicin, standard-dose cytarabine and etoposide (ICE), followed by an early consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). For second consolidation, patients ≤ 55years are stratified into three treatment arms:

  1. 1.

    low-risk, defined by t(8;21), inv(16), t(15;17): HAM;

  2. 2.

    intermediate-risk, normal karyotype: allogeneic bone marrow transplantation (BMT) for patients with an HLA-identical sibling, or S-HAM; and

  3. 3.

    high-risk, all other chromosome aberrations: allogeneic or autologous BMT.

Patients older than 55 years are treated according the low-risk arm. At present, 172 patients (median age: 44 years; range: 16–60 years) are eligible. Central cytogenetic diagnosis which included chromosome banding analysis and molecular screening by fluorescence in situ hybridization was successful in 167 of the 172 (97%) leukemias. Complete remission (CR) rates were 98, 81 and 56% for the low-, intermediate- and high-risk group, respectively. The estimated disease-free survival (DFS) at 1.5 years is 67, 58 and 45% for the respective groups. In conclusion, the results confirm the high predictive value of the karyotype for achieving a CR. Although the median follow-up time is short, our preliminary data suggest that intensive double induction chemotherapy with ICE and postremission therapy that is stratified according to the karyotype may improve DFS for the intermediate- and high-risk leukemias.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

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. Mitelman F, Kaneko Y, Berger R (1995) Report of the committee on chromosome changes in neoplasia, in Cuticchia AJ, Pearson PL (eds) Human gene mapping. Baltimore, MD, John Hopkins, p 773

    Google Scholar 

  2. Mrózek K, Heinonen K, de la Chapelle A, Bloomfield CD (1997) Clinical significance of cytogenetics in acute myeloid leukemia. Sem Oncol 24: 17

    Google Scholar 

  3. Bloomfield CD, Lawrence D, Arthur DC, Berg DT, Schiffer CA, Mayer RJ (1994) Curative impact of intensification with high-dose cytarbine (HiDAC) in acute myeloid leukemia (AML) varies by cytogenetic group. Blood 84:llla, (abstr.)

    Google Scholar 

  4. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1985) Proposed revised criteria for the classification of acute myeloid leukemia. A report of the FrenchAmerican-British Cooperative Group. Ann Intern Med 103: 620

    Google Scholar 

  5. Döhner H, Arthur DC, Ball ED, Sobol RE, Davey FR, Lawrence D, Gordon L, Patil SR, Surana RB, Testa JR, Verma RS, Schiffer CA, Wurster-Hill DH, Bloomfield CD (1990) Trisomy 13–A new recurring chromosome abnormality in acute leukemia. Blood 76: 1614–1621

    PubMed  Google Scholar 

  6. Fischer K, Scholl C, Sàlat J, Fröhling S, Schlenk R, Bentz M, Stilgenbauer S, Lichter P, Döhner H (1996) Design and validation of DNA probe sets for a comprehensive interphase cytogenetic analysis of acute myeloid leukemia. Blood 88: 3962–3971

    PubMed  CAS  Google Scholar 

  7. Avvisati G, Lo Coco F, Diverio D, Falda M, Ferrara F, Lazzarino M, Russo D, Petti MC, Mandelli F (1996) AIDA (all-trans retinoic acid + idarubicin) in newly diagnosed acute promyelocytic leukemia: a Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto ( GIMEMA) pilot study. Blood 88: 1390

    Google Scholar 

  8. Schlenk R, Döhner H, Pförsich M, Benner A, Fischer K, Fischer JTh, Weber W, Gunzer U, Pralle H, Haas R: Collection of peripheral blood progenitor cells in patients with acute myeloid leukemia following intensive double induction with ICE and consolidation therapy with granulocyte-colony-stimulating factor supported high-dose cytarabine and mitoxantrone. Submitted

    Google Scholar 

  9. Hiddemann W, Büchner Th, Essink M, Koch O, Stenzinger W, van de Loo J (1988) High-dose cytosine arabinoside and mitoxantrone: preliminary results of a pilot study with sequential application ( S-HAM) indicating a high antileukemic activity in refractory acute leukemias. Oncologie 11: 10–12

    Google Scholar 

  10. Berman E, Heller G, Santorsa J, McKenzie S, Gee T, Kempin S, Gulati S, Andreeff M, Kolitz J, Gabrilove J, Reich L, Mayer K, Keefe D, Trainor K, Schluger A, Penenberg D, Raymond V, O’Reilly R, Jhanwar S,Young C, Clarkson B (1991) Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. Blood 77: 1666–1674

    CAS  Google Scholar 

  11. Wiernik PH, Banks PLC, Case Jr DC, Arlin ZA, Periman PO, Todd MB, Ritch PS, Enck RE, Weit-berg AB (1992) Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia. Blood 79: 313–319

    PubMed  CAS  Google Scholar 

  12. Vogler WR, Velez-Garcia E, Weiner RS, Flaum MA, Bartolucci AA, Omura GA, Gerber MC, Banks PLC (1992) A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group study. J Clin Oncol 10: 1103–1111

    PubMed  CAS  Google Scholar 

  13. Wheatley K (1995) Meta-analysis of randomised trials of idarubicin (IDAR) or mitoxantrone (MITO) vs daunorubicin (DNR) as induction therapy for acute myeloid leukemia (AML). Blood 86: 434a, (abstr)

    Google Scholar 

  14. Bishop JF, Joshua D, Lowenthal RM, Matthews JP, Todd D, Cobcroft R, Whiteside MG, Kronenberg H, Ma D, Dodds A, Herrmann R, Szer J, Wolf MM, Young GA (1990) Etoposide in acute nonlymphocytic leukemia. Blood 75: 27

    PubMed  CAS  Google Scholar 

  15. Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, Omura GA, Moore JO, McIntyre OR, Frei III E (1994) Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med 331: 896

    Article  PubMed  CAS  Google Scholar 

  16. Zittoun RA, Mandelli F, Willemze R, De Witte T, Labar B,Resegotti L,Leoni F, Damasi E,Visani G, Papa G, Caronia F, Hayat M, Stryckmans P, Rotoli B, Leoni P, Peetermans ME, Dardenne M, Veg-na ML, Petti MC, Solbu G, Stefan Suciu, for the European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto (GIMEMA) (1995). N Engl J Med 332: 217–223

    Google Scholar 

  17. Büchner T, Hiddemann W, Schaefer UW, Löffler G, Maschmeyer G, Ludwig WD, Aul C, Lathan B, Heinecke A (1992) Combined effect of very early intensification and prolonged postremission chemotherapy in patients with AML. Leukemia 5 (Supp14): 68–70

    Google Scholar 

  18. Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, Bickers JN, Hynes HE, Welborn JL, Simon SR, Grever M (1996) A randomized investigation of high-dose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group Study. Blood 88: 2841–2851

    PubMed  CAS  Google Scholar 

  19. Burnett AK, Goldstone AH, Stevens RF, Hann IM, Rees JK, Wheatley K, Gray RG (1994) The role of BMT in addition to intensive chemotherapy in AML in first CR: Results of the MRC AML-10 trial. Blood 84: 252a

    Google Scholar 

  20. Schiffer CA, Lee EJ, Tomiyasu T, Wiernik PH, Testa JR (1989) Prognostic impact of cytogenetic abnormalities in patients with de novo acute nonlymphocytic leukemia. Blood 73: 263–270

    PubMed  CAS  Google Scholar 

  21. Marosi C, Köller U, Koller-Weber E, Schwarzinger I, Schneider B, Jäger U, Vahls P, Nowotny H, Pirc-Danoewinata H, Steger G, Kreiner G, Wagner B, Lechner K, Lutz D, Bettelheim P, Haas OA (1992) Prognostic impact of karyotype and immunologic phenotype in 125 adult patients with de novo AML. Cancer Genet Cytogenet 61: 14–25

    Article  PubMed  CAS  Google Scholar 

  22. Stasi R, Del Poeta G, Masi M, Tribalto M,Venditti A, Papa G, Nicoletti B, Vernole P, Tedeschi B, Delaroche I, Mingarelli R, Dallapiccola B (1993) Incidence of chromosome abnormalities and clinical significance of karyotype in de novo acute myeloid leukemia. Cancer Genet Cytogenet 67: 28–34

    Article  PubMed  CAS  Google Scholar 

  23. Dastugue N, Payen C, Lafage-Pochitaloff M, Bernard P, Leroux D, Huguet-Rigal F, Stoppa AM, Marit G, Molina L, Michallet M, Maraninchi D, Attal M, Reiffers J for the BGMT group (1995) Prognostic significance of karyotype in de novo adult acute myeloid leukemia. Leukemia 9: 1491 1498

    Google Scholar 

  24. Joventino LP, Stock W, Lane NJ, Daly KM, Mick R, Le Beau MM, Larson RA (1995) Certain HLA antigens are associated with specific morphologic and cytogenetic subsets of acute myeloid leukemia. Leukemia 9: 433–439

    PubMed  CAS  Google Scholar 

  25. Byrd JC, Lawrence D, Arthur DC, Davey F, Schiffer CA, Bloomfield CD (1996) Acute myeloid leukemia (AML) patients with pre-treatment isolated trisomy 8 are rarely cured with chemotherapy (1996) results of CALGB 8461. Proc Am Assoc Cancer Res 37: 188 (abstr)

    Google Scholar 

  26. Grimwade D, Walker H, Harrison C, Oliver F, Wheatley K, Harrison G, Gray R, Hann I, Stevens R, Rees J, Goldstone A, Burnett A, on behalf of the Medical Research Council Leukaemia Working Parties (1996) Impact of diagnostic cytogenetics on outcome in AML: Analysis of 1,613 patients entered into the UK MRC AML-10 trial. Blood 88: 634a (abstr)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Schlenk, R. et al. (1998). Stratification of Postremission Therapy in Adult Acute Myeloid Leukemia According to the Karyotype — Preliminary Results of the Multicenter Treatment Trial AML HD93. In: Hiddemann, W., et al. Acute Leukemias VII. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 39. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71960-8_119

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-71960-8_119

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-71962-2

  • Online ISBN: 978-3-642-71960-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics