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Current Issues in Adult AML

Allogeneic BMT for AML

Appelbaum spacer
Frederick R. Appelbaum, MD
Director, Clinical Research Division
Member, Fred Hutchinson Cancer
Research Center

Because allogeneic bone marrow transplantation is the only therapy capable of achieving cure in patients with AML who fail induction therapy,1,2 all patients 55 years of age or less with newly diagnosed AML and their families should be HLA-typed soon after diagnosis to enable transplantation should induction fail. Allogeneic transplantation is indicated in patients in second remission and in untreated first relapse, since the results (see table below) are superior to those achieved without transplantation3-5 Patients transplanted in first remission achieve the highest cure rates.

Success rates with allogeneic bone marrow transplantation in patients with AML1-7
Patients Estimated Cure Rate
Patients who fail induction therapy 15-20%
Patients in second remission 30%
Patients in untreated first relapse 35%
Patients in first remission 40-70%

Numerous prospective studies have compared marrow transplantation in patients with HLA-matched siblings to chemotherapy in patients without such siblings (see table below). However, there have been important advances in both chemotherapy and transplantation since the conduct of most of these studies. In addition, these studies did not distinguish between different categories of patients. Retrospective studies have suggested that there may be certain categories of patients for whom transplantation may be a particular advantage and others for whom it may be of less benefit. Finally, it remains untested whether a strategy of transplantation in first remission is superior to the combination of initial chemotherapy followed by transplantation as salvage therapy.

Comparative success rates of bone marrow transplantation and chemotherapy in patients with AML
Therapy Estimated Success Rate
14 prospective comparative studies
(published 1984-1994)8-22

Allogeneic bone marrow transplantation 40-64%
Chemotherapy 19-24%
Recent prospective study28 Disease-free survival at 4 yrs
Allogeneic marrow transplantation 54%
Autologous marrow transplantation 49%
Continued chemotherapy 30%

Autologous marrow transplantation for patients with AML in first and second remission in several phase II studies has yielded promising results.23-27 In the largest prospective randomized study so far reported, 569 patients with AML in first remission were assigned to allogeneic transplantation if HLA-matched siblings were available, or were randomized to autologous transplantation or continued chemotherapy if donors were not available.28 Promising results were obtained with transplantation as compared to chemotherapy.

Conclusions

  • Study results of allogeneic bone marrow transplantation are most favorable in patients transplanted in first remission.
  • All patients 55 years of age or less with newly diagnosed AML should be HLA-typed soon after diagnosis, since allogeneic BMT is the only therapy to achieve cure (estimated in 15% to 20% of patients studied)1-7 should induction therapy fail.
  • Results of a large, prospective randomized study of patients in first remission confirm findings of earlier prospective studies that allogeneic bone marrow transplantation improves disease-free survival compared to chemotherapy.

References

  1. Biggs JC, Horowitz MM, Gale RP, et al. Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood. 1992;80:1090-1093.
  2. Forman SJ, Schmidt GM, Nademanee AP, et al. Allogeneic bone marrow transplantation as therapy for primary induction failure for patients with acute leukemia. J Clin Oncol. 1991;9:1570-1574.
  3. Clift RA, Buckner CD, Thomas ED, et al. The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation. Bone Marrow Transplant. 1987;2:243-258.
  4. Appelbaum FR, Clift RA, Buckner CD, et al. Allogeneic marrow transplantation for acute nonlymphoblastic leukemia after first relapse. Blood 1983;61:949-953.
  5. 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.
  6. Thomas ED, Buckner CD, Clift RA, et al. Marrow transplantation for acute nonlymphoblastic leukemia in first remission. N Engl J Med. 1979;301:597-599.
  7. Blume KG, Beutler E, Bross KJ, et al. Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med. 1980;302:1041-1046.
  8. Appelbaum FR, Dahlberg S, Thomas ED, et al. Bone marrow transplantation or chemotherapy after remission induction for adults with acute nonlymphoblastic leukemia: A prospective comparison. Ann Intern Med. 1984;101:581-588.
  9. Appelbaum FR, Fisher LD, Thomas ED, and the Seattle Marrow Transplant Team: Chemotherapy v marrow transplantation for adults with acute nonlymphocytic leukemia: A five-year follow-up. Blood. 1988;72:179-184.
  10. Champlin RE, Ho WG, Gale RP, et al. Treatment of acute myelogenous leukemia. A prospective controlled trial of bone marrow transplantation versus consolidation chemotherapy. Ann Intern Med. 1985;102:285-291.
  11. Marmont A, Bacigalupo A, Van Lint MT, Frassoni F, Carella A. Bone marrow transplantation versus chemotherapy alone for acute nonlymphoblastic leukemia. Exp Hematol. 1985;13(suppl 17):40.
  12. Zander AR, Keating M, Dicke K, et al. A comparison of marrow transplantation with chemotherapy for adults with acute leukemia of poor prognosis in first complete remission. J Clin Oncol. 1988;6:1548-1557.
  13. Conde E, Iriondo A, Rayon C, et al. Allogeneic bone marrow transplantation versus intensification chemotherapy for acute myelogenous leukaemia in first remission: a prospective controlled trial. Br J Haematol. 1988;68:219-226.
  14. Reiffers J, Gaspard MH, Maraninchi D, et al. Comparison of allogeneic or autologous bone marrow transplantation and chemotherapy in patients with acute myeloid leukaemia in first remission: a prospective controlled trial. Br J Haematol. 1989;72:57-63.
  15. Ringdén O, Bolme P, Lönnqvist B, Gustafsson G, Kreuger A. Allogeneic bone marrow transplantation versus chemotherapy in children with acute leukemia in Sweden. Pediatr Hematol Oncol. 1989;6:137-144.
  16. Dahl GV, Kalwinsky DK, Mirro J Jr, et al. Allogeneic bone marrow transplantation in a program of intensive sequential chemotherapy for children and young adults with acute nonlymphocytic leukemia in first remission. J Clin Oncol. 1990;8:295-303.
  17. Schiller GJ, Nimer SD, Territo MC, Ho WG, Champlin RE, Gajewski JL. Bone marrow transplantation versus high-dose cytarabine-based consolidation chemotherapy for acute myelogenous leukemia in first remission. J Clin Oncol. 1992;10:41-46.
  18. Cassileth PA, Lynch E, Hines JD, et al. Varying intensity of postremission therapy in acute myeloid leukemia. Blood. 1992;79:1924-1930.
  19. Amadori S, Testi AM, Aricň M, et al. Prospective comparative study of bone marrow transplantation and postremission chemotherapy for childhood acute myelogenous leukemia. J Clin Oncol. 1993;11: 1046-1054.
  20. Nesbit ME Jr, Buckley JD, Feig SA, et al. Chemotherapy for induction of remission of childhood acute myeloid leukemia followed by marrow transplantation or multiagent chemotherapy: a report from the Childrens Cancer Group. J Clin Oncol. 1994;12:127-135.
  21. Archimbaud E, Thomas X, Michallet M, et al. Prospective genetically randomized comparison between intensive postinduction chemotherapy and bone marrow transplantation in adults with newly diagnosed acute myeloid leukemia. J Clin Oncol. 1994;12:262-267.
  22. Hewlett J, Kopecky JK, Head D, et al. A prospective evaluation of the roles of allogeneic marrow transplantation and low-dose monthly maintenance chemotherapy in the treatment of adult acute myelogenous leukemia (AML): A Southwest Oncology Group study. Leukemia, in press.
  23. Yeager AM, Kaizer H, Santos GW, et al. Autologous bone marrow transplantation in patients with acute nonlymphocytic leukemia, using ex vivo marrow treatment with 4-hydroperoxycyclophosphamide. N Engl J Med. 1986;315:141-147.
  24. Lowenberg B, Verdonck LJ, Dekker AW, et al. Autologous bone marrow transplantation in acute myeloid leukemia in first remission: results of a Dutch prospective study. J Clin Oncol. 1990;8:287-294.
  25. Chao NJ, Stein AS, Long GD, et al. Busulfan/etoposide-initial experience with a new preparatory regimen for autologous bone marrow transplantation in patients with acute nonlymphoblastic leukemia. Blood. 1993;81:319-323.
  26. Ball ED, Mills LE, Cornwell GG III, et al. Autologous bone marrow transplantation for acute myeloid leukemia using monoclonal antibody-purged bone marrow. Blood. 1990;75:1199-1206. 27. Petersen FB, Lynch MHE, Clift RA, et al. Autologous marrow transplantation for patients with acute myeloid leukemia in untreated first relapse or in second complete remission. J Clin Oncol. 1993;11:1353-1360.
  27. Zuttoun R, Mandelli F, Willemze R, et al. Prospective phase III study of autologous bone marrow transplantation (ABMT) v short intensive chemotherapy (IC) v allogeneic bone marrow transplantation (ALLO-BMT) during first complete remission (CR) of acute myelogenous leukemia (AML). Results of the EORTC-GIMEMA AML 8A trial. Blood. 1993;82(suppl 1):85a. Abstract.


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