Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Therapy

An effective chemotherapeutic regimen for acute myeloid leukemia and myelodysplastic syndrome in children with Down's syndrome

Leukemia volume 14, pages 786–791 (2000)Cite this article

Abstract

In recent pediatric collaborative studies of acute myeloid leukemia (AML), patients with Down's syndrome (DS) have better outcome than other patients when they were treated according to their intensive AML protocols. This may be attributed to enhanced sensitivity of DS AML cells to selected chemotherapeutic agents. We evaluated a less intensive chemotherapeutic regimen which was specifically designed for children with AML-DS. Remission induction chemotherapy consisted of daunorubicin (25 mg/m2/day for 2 days), cytosine arabinoside (100 mg/m2/day for 7 days), and etoposide (150 mg/m2/day for 3 days). Patients received one to seven courses of consolidation therapy of the same regimen. Thirty-three patients were enrolled on the study and their clinical, hematologic and immunophenotypic features were analyzed. Of the 33 patients, all were younger than 4 years and diagnosed as having acute megakaryoblastic leukemia or myelodysplastic syndrome. All patients achieved a complete remission and estimated 8 year event-free survival rate was 80 ± 7%. Three patients relapsed and two died due to cardiac toxicity and one due to septic shock. The results of our study showed that patients with AML-DS constitute a unique biologic subgroup and should be treated according to a less intensive protocol designed for AML-DS.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Robinson LL . Down syndrome and leukemia Leukemia 1992 6: 5–7

    Google Scholar 

  2. Avet-Loiseau H, Mechinaud F, Harousseau J-L . Clonal hematologic disorders in Down syndrome J Pediatr Hematol Oncol 1995 17: 19–24

    Article  CAS  Google Scholar 

  3. Kojima S, Matsuyama T, Sato T, Horibe K, Konishi S, Tsuchida M, Hayash Y, Kigasawa H, Akiyama Y, Okamura J, Nakahata T, Bessho F, Eguchi M, Nakazawa S, Ueda R . Down's syndrome and acute leukemia in children: an analysis of phenotype by use of monoclonal antibodies and electron microscopic platelet peroxidase reaction Blood 1990 76: 2348–2353

    CAS  PubMed  Google Scholar 

  4. Ravindranath Y, Abella E, Krischer JP, Wiley J, Inoue S, Harris M, Chauvenet A, Alvarado CS, Dubowy R, Ritchey AK, Land V, Steuber CP, Weinstein H . Acute myeloid luekemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498 Blood 1992 80: 2210–2214

    CAS  PubMed  Google Scholar 

  5. Lie SO, Jonmundsson G, Mellander L, Siimes MA, Yssing M, Gustafsson G . A population-based study of 272 children with acute myeloid leukaemia treated on two consecutive protocols with different intensity: best outcome in girls, infants, and children with Down's syndrome Br J Haematol 1996 94: 82–88

    Article  CAS  Google Scholar 

  6. Creutzig U, Ritter J, Vormoor J, Ludwig WD, Niemeyer C, Reinisch I, Stollmann-Gibbels B, Zimmermann M, Harbott J . Myelodysplasia and acute myelogenous leukemia in Down's syndrome. A report of 40 children of the AML-BFM study group Leukemia 1996 10: 1677–1686

    CAS  PubMed  Google Scholar 

  7. Stevens RF, Hann IM, Wheatley K, Gray RG . Marked improvements in outcome with chemotherapy alone in paediatric acute myeloid leukaemia: results of the United Kingdom Medical Research Council's 10th AML trial Br J Haematol 1998 101: 130–140

    Article  CAS  Google Scholar 

  8. Lange BJ, Kobrinsky N, Barnard DR, Arthur DC, Buckley JD, Howells WB, Gold S, Sanders J, Neudorf S, Smith FO, Woods WG . Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children's Cancer Group Studies 2861 and 2891 Blood 1998 91: 608–615

    CAS  PubMed  Google Scholar 

  9. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C . The French–American–British (FAB) Co-operative Group: Proposals for the classification of the myelodysplastic syndromes Br J Haematol 1982 51: 189–199

    Article  CAS  Google Scholar 

  10. Eguchi M, Sakakibara H, Suda J, Ozawa T, Hayashi Y, Sato T, Kojima S, Furukawa T . Ultrastructural and ultracytochemical differences between transient myeloproliferative disorder and megakaryoblastic leukaemia in Down's syndrome Br J Haematol 1989 73: 315–332

    Article  CAS  Google Scholar 

  11. Kaplan EL, Meier P . Non-parametric estimation from incomplete observations J Am Stat Assoc 1958 53: 457–481

    Article  Google Scholar 

  12. Cheson BD, Cassileth PA, Head DR, Schiffer CA, Bennett JM, Bloomfield CD, Brunning R, Gale RP, Grever MR, Keating MJ . Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia J Clin Oncol 1990 8: 813–819

    Article  CAS  Google Scholar 

  13. Yumura-Yagi K, Hara J, Kurahashi H, Nishiura T, Kaneyama Y, Osugi Y, Sakata N, Inoue M, Tawa A, Okada S, Kawa-Ha K . Mixed phenotype of blasts in acute megakaryocytic leukaemia and transient abnormal myelopoiesis in Down's syndrome Br J Haematol 1992 81: 520–525

    Article  CAS  Google Scholar 

  14. Slordahl SH, Smeland EB, Holte H, Gronn M, Lie SO, Seip M . Leukemic blasts with markers of four cell lineages in Down's syndrome (‘Megakaryoblastic Leukemia’) Med Pediatr Oncol 1993 21: 254–258

    Article  CAS  Google Scholar 

  15. Okumura N, Tsuji K, Nakahata T . Changes in cell surface antigen expressions during proliferation and differentiation of human erythroid progenitors Blood 1992 80: 642–650

    CAS  PubMed  Google Scholar 

  16. Ito E, Kasai M, Hayashi Y, Toki T, Arai K, Yokoyama S, Kato K, Tachibana N, Yamamoto M, Yokoyama M . Expression of erythroid-specific genes in acute megakaryoblastic leukaemia and transient myeloproliferative disorder in Down's syndrome Br J Haematol 1995 90: 607–614

    Article  CAS  Google Scholar 

  17. Kita K, Miwa H, Nakase K, Kawakami K, Kobayashi T, Shirakawa S, Tanaka I, Ohta C, Tsutani H, Oguma S, Kyo T, Dohy H, Kamada N, Nasu K, Uchino H . Clinical importance of CD7 expression in acute myelocytic leukemia Blood 1993 81: 2399–2405

    CAS  PubMed  Google Scholar 

  18. Creutzig U, Harbott J, Sperling C, Ritter J, Zimmermann M, Loffler H, Riehm H, Schellong G, Ludwig W-D . Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of Study AML-BFM-87 Blood 1995 86: 3097–3108

    CAS  PubMed  Google Scholar 

  19. McDonald JP, Sullivan PS . Megakaryocytic and erythrocytic cell lines share a common precursor cell Exp Hematol 1993 21: 1316–1328

    CAS  PubMed  Google Scholar 

  20. Skipper HE, Schable JM, Wilcox WS . Experimental evaluation of potential anticancer agents: scheduling of arabinosylcytosine to take advantage of its S-phase specificity against leukemia cells Cancer Chemother Rep 1967 51: 125–165

    CAS  PubMed  Google Scholar 

  21. Taub JW, Matherly LH, Stout ML, Buck SA, Gurney JG, Ravindranath Y . Enhanced metabolism of 1-β-D-arabinofuranosylcytosine in Down syndrome cells: a contributing factor to the superior event free survival of Down syndrome children with acute myeloid leukemia Blood 1996 87: 3395–3403

    CAS  PubMed  Google Scholar 

  22. Fong C, Brodeur GM . Down's syndrome and leukemia: epidemiology, genetics, cytogenetics and mechanisms of leukemogenesis Cancer Genet Cytogenet 1987 28: 55–76

    Article  CAS  Google Scholar 

  23. Gilladoga AC, Manuel C, Tan CTC, Wollner N, Sternberg SS, Murphy ML . The cardiotoxicity of adriamycin and daunomycin in children Cancer 1976 37: 1070–1078

    Article  CAS  Google Scholar 

  24. Lewis AB, Pilkington R, Takahashi M, Siegel SE . Echocardiographic assessment of anthracycline cardiotoxicity in children Med Pediatr Oncol 1978 5: 167–175

    Article  CAS  Google Scholar 

  25. Lipshultz SE, Colan SD, Gelber RD, Perez-Atayde AR, Sallan SE, Sanders SP . Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood New Engl J Med 1991 324: 808–815

    Article  CAS  Google Scholar 

  26. Hayashi Y, Eguchi M, Sugita K, Nakazawa S, Sato T, Kojima S, Bessho F, Konishi S, Inaba T, Hanada R, Yamamoto K . Cytogenetic findings and clinical features in acute leukemia and transient myeloproliferative disorder in Down's syndrome Blood 1988 72: 15–23

    CAS  PubMed  Google Scholar 

  27. Haas OA, Gadner H . Pathogenesis, biology, and management of myelodysplastic syndromes in children Semin Hematol 1996 33: 225–235

    CAS  PubMed  Google Scholar 

  28. Woods WG, Nesbit ME, Buekley J, Lampkin BC, McCreadie S, Kim TH, Piomelli S, Kersy JH, Feig S, Bernstein I, Hammond D, the Children's Cancer Study Group . Correlation of chromosome abnormalities with patient characteristics, histologic subtype, and induction success in children with acute nonlymphocytic leukemia J Clin Oncol 1985 3: 3–11

    Article  CAS  Google Scholar 

  29. Kalwinsky DK, Raimondi SC, Schell MJ, Mirro JJ, Santana VM, Behm F, Dahl GV, Williams D . Prognostic importance of cytogenetic subgroups in de novo pediatric acute nonlymphocytic leukemia J Clin Oncol 1990 8: 75–83

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Developmental Pediatrics, Nagoya University School of Medicine, Japan

    S Kojima

  2. Department of Pediatrics, Osaka City General Hospital, Osaka, Japan

    M Sako & G Hosoi

  3. Division of Hematology/Oncology, Children's Medical Center, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    K Kato

  4. Department of Pediatrics, School of Medicine, Chiba University, Chiba, Japan

    T Sato

  5. First Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan

    A Ohara & I Tsukimoto

  6. Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan

    K Koike

  7. Division of Hematology/Oncology, Chiba Children's Hospital, Chiba, Japan

    Y Okimoto

  8. Department of Pediatrics, Hiroshima University School of Medicine, Hiroshima, Japan

    S Nishimura & K Ueda

  9. Department of Pediatrics, School of Medicine, Kyoto University, Kyoto, Japan

    Y Akiyama

  10. Department of Pediatrics, Fujita Health University School of Medicine, Toyoake, Japan

    T Yoshikawa

  11. Department of Pediatrics, Hamanomachi Hospital, Fukuoka, Japan

    E Ishii

  12. Section of Pediatrics, National Kyushu Cancer Center, Fukuoka, Japan

    J Okamura

  13. Department of Pediatrics, Nagoya City University Medical School, Nagoya, Japan

    M Yazaki

  14. Department of Pediatrics, University of Tokyo, Tokyo, Japan

    Y Hayashi

  15. Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan

    M Eguchi

Authors
  1. S Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Sako
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Hosoi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Ohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K Koike
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y Okimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Y Akiyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T Yoshikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. E Ishii
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J Okamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. M Yazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Y Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. M Eguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. I Tsukimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. K Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kojima, S., Sako, M., Kato, K. et al. An effective chemotherapeutic regimen for acute myeloid leukemia and myelodysplastic syndrome in children with Down's syndrome. Leukemia 14, 786–791 (2000). https://doi.org/10.1038/sj.leu.2401754

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2401754

Keywords

This article is cited by

Search

Advanced search

Quick links