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Allografting

Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia

Summary:

Allogeneic bone marrow transplantation (BMT) may offer the only chance of cure for children with acute myeloid leukemia (AML) in second complete remission (CR2) or with relapsed disease, but the outcome of these patients has not been clearly defined. We conducted a retrospective study of 58 children, median age 7.4 years (range 0.8–17.3), who received matched related or unrelated BMT at our institution for AML in CR2 (n=12), in untreated first relapse (n=11) or with refractory disease (n=35), to identify risk factors associated with disease-free survival (DFS). Life threatening to fatal regimen-related toxicity was observed in 22% of patients. Estimates of DFS at 5 years (95% confidence interval) for patients in CR2, with untreated first relapse and refractory disease were 58% (27–80%), 36% (11–63%) and 9% (2–21%), respectively. Non-relapse mortality estimates were 0%, 27% (0–54%) and 17% (5–30%), and relapse estimates were 42% (14–70%), 36% (8–65%) and 74% (60–89%), respectively. Advanced disease phase and cytogenetic abnormalities at the time of transplantation were each associated with decreased DFS and increased relapse in multivariable regression models. Survival for children transplanted in CR2 or untreated first relapse is higher than that previously reported, but relapse remains the major cause of treatment failure regardless of disease stage.

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References

  1. Woods WG, Neudorf S, Gold S et al. A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood 2001; 97: 56–62.

    Article  CAS  PubMed  Google Scholar 

  2. Amadori S, Testi AM, Arico M et al. Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica Cooperative Group. J Clin Oncol 1993; 11: 1046–1054.

    Article  CAS  PubMed  Google Scholar 

  3. Burnett AK, Wheatley K, Goldstone AH et al. The value of allogeneic bone marrow transplant in patients with acute myeloid leukaemia at differing risk of relapse: results of the UK MRC AML 10 trial. Br J Haematol 2002; 118: 385–400.

    Article  PubMed  Google Scholar 

  4. Feig SA, Lampkin B, Nesbit ME et al. Outcome of BMT during first complete remission of AML: a comparison of two sequential studies by the Children's Cancer Group. Bone Marrow Transplant 1993; 12: 65–71.

    CAS  PubMed  Google Scholar 

  5. Wells RJ, Woods WG, Buckley JD et al. Treatment of newly diagnosed children and adolescents with acute myeloid leukemia: a Children's Cancer Group study. J Clin Oncol 1994; 12: 2367–2377.

    Article  CAS  PubMed  Google Scholar 

  6. Ravindranath Y, Yeager AM, Chang MN et al. Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. Pediatric Oncology Group. N Engl J Med 1996; 334: 1428–1434.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  8. Fleischhack G, Hasan C, Graf N et al. IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial. Br J Haematol 1998; 102: 647–655.

    Article  CAS  PubMed  Google Scholar 

  9. Dini G, Boni L, Abla O et al. Allogeneic bone marrow transplantation in children with acute myelogenous leukemia in first remission. Bone Marrow Transplant 1994; 13: 771–776.

    CAS  PubMed  Google Scholar 

  10. Schiller G, Feig SA, Territo M et al. Treatment of advanced acute leukaemia with allogeneic bone marrow transplantation from unrelated donors. Br J Haematol 1994; 88: 72–78.

    Article  CAS  PubMed  Google Scholar 

  11. Aladjidi N, Auvrignon A, Leblanc T et al. Outcome in children with relapsed acute myeloid leukemia after initial treatment with the French Leucemie Aique Myeloide Enfant (LAME) 89/91 protocol of the French Society of Pediatric Hematology and Immunology. J Clin Oncol 2003; 21: 4377–4385.

    Article  CAS  PubMed  Google Scholar 

  12. Webb DK, Wheatley K, Harrison G et al. Outcome for children with relapsed acute myeloid leukaemia following initial therapy in the Medical Research Council (MRC) AML 10 trial. MRC Childhood Leukaemia Working Party. Leukemia 1999; 13: 25–31.

    Article  CAS  PubMed  Google Scholar 

  13. Sierra J, Storer B, Hansen JA et al. Unrelated donor marrow transplantation for acute myeloid leukemia: an update of the Seattle experience. Bone Marrow Transplant 2000; 26: 397–404.

    Article  CAS  PubMed  Google Scholar 

  14. Woolfrey AE, Gooley TA, Sievers EL et al. Bone marrow transplantation for children less than 2 years of age with acute myelogenous leukemia or myelodysplastic syndrome. Blood 1998; 92: 3546–3556.

    CAS  PubMed  Google Scholar 

  15. Casper J, Camitta B, Truitt R et al. Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia. Blood 1995; 85: 2354–2363.

    CAS  PubMed  Google Scholar 

  16. Davies SM, Wagner JE, Shu XO et al. Unrelated donor bone marrow transplantation for children with acute leukemia. J Clin Oncol 1997; 15: 557–565.

    Article  CAS  PubMed  Google Scholar 

  17. Balduzzi A, Gooley T, Anasetti C et al. Unrelated donor marrow transplantation in children. Blood 1995; 86: 3247–3256.

    CAS  PubMed  Google Scholar 

  18. Dinndorf P, Bunin N . Bone marrow transplantation for children with acute myelogenous leukemia. J Pediatr Hematol Oncol 1995; 17: 211–224.

    Article  CAS  PubMed  Google Scholar 

  19. Hongeng S, Krance RA, Bowman LC et al. Outcomes of transplantation with matched-sibling and unrelated-donor bone marrow in children with leukaemia. Lancet 1997; 350: 767–771.

    Article  CAS  PubMed  Google Scholar 

  20. Horowitz MM, Bortin MM . Results of bone marrow transplants from human leukocyte antigen-identical sibling donors for treatment of childhood leukemias. A report from the International Bone Marrow Transplant Registry. Am J Pediatr Hematol Oncol 1993; 15: 56–64.

    Article  CAS  PubMed  Google Scholar 

  21. Brochstein JA, Kernan NA, Groshen S et al. Allogeneic bone marrow transplantation after hyperfractionated total-body irradiation and cyclophosphamide in children with acute leukemia. N Engl J Med 1987; 317: 1618–1624.

    Article  CAS  PubMed  Google Scholar 

  22. Balduzzi A, Valsecchi MG, Silvestri D et al. Transplant-related toxicity and mortality: an AIEOP prospective study in 636 pediatric patients transplanted for acute leukemia. Bone Marrow Transplant 2002; 29: 93–100.

    Article  CAS  PubMed  Google Scholar 

  23. Bennett JM, Catovsky D, Daniel MT et al. Proposals for the classification of the acute leukaemias. French–American–British (FAB) co-operative group. Br J Haematol 1976; 33: 451–458.

    Article  CAS  PubMed  Google Scholar 

  24. Webb DK, Harrison G, Stevens RF et al. Relationships between age at diagnosis, clinical features, and outcome of therapy in children treated in the Medical Research Council AML 10 and 12 trials for acute myeloid leukemia. Blood 2001; 98: 1714–1720.

    Article  CAS  PubMed  Google Scholar 

  25. Slattery JT, Sanders JE, Buckner CD et al. Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transplant 1995; 16: 31–42.

    CAS  PubMed  Google Scholar 

  26. Hansen JA, Mickelson EM, Choo SY et al. Clinical bone marrow transplantation: donor selection and recipient monitoring. In: Rose NR, De Macario EC, Fahey JL, Friedman H, Penn GM (eds). Manual of Clinical Laboratory Immunology. American Society for Microbiology: Washington, DC, 1992, pp 850–866.

    Google Scholar 

  27. Dupont B, Yang SY . Histocompatibility. In: Forman SJ, Blume KG, Thomas ED (eds). Bone Marrow Transplantation. Blackwell Scientific: Boston, MA, 1994; pp 22–40.

    Google Scholar 

  28. Thomas ED, Storb R, Clift RA et al. Bone-marrow transplantation. N Engl J Med 1975; 292: 895–902.

    Article  CAS  PubMed  Google Scholar 

  29. Storb R, Deeg HJ, Whitehead J et al. Marrow transplantation for leukemia and aplastic anemia: two controlled trials of a combination of methotrexate and cyclosporine v cyclosporine alone or methotrexate alone for prophylaxis of acute graft-v-host disease. Transplant Proc 1987; 19: 2608–2613.

    CAS  PubMed  Google Scholar 

  30. Common Toxicity Criteria Manual Version 2, Cancer Therapy Evaluation Program, National Institutes of Health, National Cancer Institute, 1999.

  31. Doney KC, Weiden PL, Storb R, Thomas ED . Treatment of graft-versus-host disease in human allogeneic marrow graft recipients: a randomized trial comparing antithymocyte globulin and corticosteroids. Am J Hematol 1981; 11: 1–8.

    Article  CAS  PubMed  Google Scholar 

  32. Sullivan KM, Shulman HM, Storb R et al. Chronic graft-versus-host disease in 52 patients: adverse natural course and successful treatment with combination immunosuppression. Blood 1981; 57: 267–276.

    CAS  PubMed  Google Scholar 

  33. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  34. Kalbfleisch JD, Prentice RL . The Statistical Analysis of Failure Time Data. Wiley: New York, NY, 1980.

    Google Scholar 

  35. Clift RA, Buckner CD, Appelbaum FR et al. Allogeneic marrow transplantation during untreated first relapse of acute myeloid leukemia. J Clin Oncol 1992; 10: 1723–1729.

    Article  CAS  PubMed  Google Scholar 

  36. Fung HC, Stein A, Slovak M et al. A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome. Biol Blood Marrow Transplant 2003; 9: 766–771.

    Article  CAS  PubMed  Google Scholar 

  37. Sierra J, Storer B, Hansen JA et al. Transplantation of marrow cells from unrelated donors for treatment of high-risk acute leukemia: the effect of leukemic burden, donor HLA-matching, and marrow cell dose. Blood 1997; 89: 4226–4235.

    CAS  PubMed  Google Scholar 

  38. Bearman SI, Appelbaum FR, Buckner CD et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol 1988; 6: 1562–1568.

    Article  CAS  PubMed  Google Scholar 

  39. Svennilson J, Remberger M, Ringden O . Risk factors for moderate-to-severe acute graft-vs-host disease after allogeneic stem cell transplantation in children. Pediatr Transplant 2003; 7: 130–136.

    Article  PubMed  Google Scholar 

  40. Locatelli F, Uderzo C, Dini G et al. Graft-versus-host disease in children: the AIEOP-BMT Group experience with cyclosporin A. Bone Marrow Transplant 1993; 12: 627–633.

    CAS  PubMed  Google Scholar 

  41. Ferrara JL, Deeg HJ . Graft-versus-host disease. N Engl J Med 1991, 324.

  42. Thomas ED, Buckner CD, Banaji M et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood 1977; 49: 511–533.

    CAS  PubMed  Google Scholar 

  43. Jonson FL, Hartmann JR, Thomas ED et al. Marrow transplantation in treatment of children with aplastic anaemia or acute leukaemia. Arch Dis Child 1976; 51: 403–410.

    Article  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Mr Paul Hoffmeister for his assistance in data collection. This work was supported in part by Grants CA100394 and CA18029 from the National Cancer Institute, National Institutes of Health.

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Correspondence to E R Nemecek.

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Nemecek, E., Gooley, T., Woolfrey, A. et al. Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia. Bone Marrow Transplant 34, 799–806 (2004). https://doi.org/10.1038/sj.bmt.1704689

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