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High-dose melphalan with or without stem cell support before myeloablative allo-SCT for remission induction in patients with advanced relapsed or refractory AML

Abstract

Treatment strategies for relapsed/refractory AML are limited and disappointing. Recently, high-dose melphalan (HDM) chemotherapy and autologous hematopoietic SCT (HSCT) has been proposed for AML re-induction. We investigated the impact of HDM remission induction in highly advanced relapsed/refractory AML patients planned for allogeneic HSCT. A total of 23 patients with relapsed/refractory AML were prospectively scheduled for HDM with or without stem cell support followed by myeloablative allogeneic HSCT. Patients included nine individuals with a history of previous HSCT (seven allogeneic, two autologous). A total of 18 patients (78%) achieved a leukemia-free state and an additional four had substantial reduction of the initial leukemia burden warranting treatment continuation. There were no differences between patients with or without immediate stem cell support regarding mucositis or other organ toxicity. A total of 20 patients proceeded to myeloablative allogeneic HSCT. Outcome of allogeneic HSCT was poor: 11 patients (55%) relapsed, 7 patients (35%) died from TRM and only 2 patients (10%) were alive at the last follow-up. Our study shows that HDM is effective in inducing a leukemia-free state in patients with highly advanced relapsed/refractory AML. Leukemia burden reduction with HDM, however, did not translate into improved OS.

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References

  1. Estey E, Dohner H . Acute myeloid leukaemia. Lancet 2006; 368: 1894–1907.

    Article  PubMed  Google Scholar 

  2. Sarosy G, Leyland-Jones B, Soochan P, Cheson BD . The systemic administration of intravenous melphalan. J Clin Oncol 1988; 6: 1768–1782.

    Article  CAS  PubMed  Google Scholar 

  3. Lemoli RM, D’Addio A, Marotta G, Pezzullo L, Zuffa E, Montanari M et al. BU/melphalan and auto-SCT in AML patients in first CR: a ‘Gruppo Italiano Trapianto di Midollo Osseo (GITMO)’ retrospective study. Bone Marrow Transplant 2010; 45: 640–646.

    Article  CAS  PubMed  Google Scholar 

  4. Mascret B, Maraninchi D, Gastaut JA, Camerlo J, Novakovitch G, Perrimond H et al. Repeated high-dose-melphalan with autologous bone marrow transplantation in acute non lymphocytic leukemia. Rev Fr Transfus Immunohematol 1985; 28: 477–488.

    Article  CAS  PubMed  Google Scholar 

  5. Tiedemann K, Waters KD, Tauro GP, Tucker D, Ekert H . Results of intensive therapy in childhood acute myeloid leukemia, incorporating high-dose melphalan and autologous bone marrow transplantation in first complete remission. Blood 1993; 82: 3730–3738.

    CAS  PubMed  Google Scholar 

  6. Maraninchi D, Pico JL, Hartmann O, Gastaut JA, Kamioner D, Hayat M et al. High-dose melphalan with or without marrow transplantation: a study of dose-effect in patients with refractory and/or relapsed acute leukemias. Cancer Treat Rep 1986; 70: 445–448.

    CAS  PubMed  Google Scholar 

  7. de Lima M, van Besien K, Gajewski J, Khouri I, Andersson B, Korbling M et al. High-dose melphalan and allogeneic peripheral blood stem cell transplantation for treatment of early relapse after allogeneic transplant. Bone Marrow Transplant 2000; 26: 333–338.

    Article  CAS  PubMed  Google Scholar 

  8. Bug G, Atta J, Klein SA, Hertenstein B, Bergmann L, Boehrer S et al. High-dose melphalan is an effective salvage therapy in acute myeloid leukaemia patients with refractory relapse and relapse after autologous stem cell transplantation. Ann Hematol 2005; 84: 748–754.

    Article  CAS  PubMed  Google Scholar 

  9. Stussi G, Halter J, Tichelli A, Meyer-Monard S, Buser AS, Arber C et al. Double allogeneic hematopoietic SCT as a rescue therapy for poor-risk hematological malignancies. Bone Marrow Transplant 2010; 45: 103–109.

    Article  CAS  PubMed  Google Scholar 

  10. Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003; 21: 4642–4649.

    Article  PubMed  Google Scholar 

  11. Moreau P, Fiere D, Bezwoda WR, Facon T, Attal M, Laporte JP et al. Prospective randomized placebo-controlled study of granulocyte-macrophage colony-stimulating factor without stem-cell transplantation after high-dose melphalan in patients with multiple myeloma. J Clin Oncol 1997; 15: 660–666.

    Article  CAS  PubMed  Google Scholar 

  12. Michallet M, Thomas X, Vernant JP, Kuentz M, Socie G, Esperou-Bourdeau H et al. Long-term outcome after allogeneic hematopoietic stem cell transplantation for advanced stage acute myeloblastic leukemia: a retrospective study of 379 patients reported to the Société Française de Greffe de Moelle (SFGM). Bone Marrow Transplant 2000; 26: 1157–1163.

    Article  CAS  PubMed  Google Scholar 

  13. Estey EH . Treatment of relapsed and refractory acute myelogenous leukemia. Leukemia 2000; 14: 476–479.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to A O'Meara.

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O'Meara, A., Pabst, T., Heim, D. et al. High-dose melphalan with or without stem cell support before myeloablative allo-SCT for remission induction in patients with advanced relapsed or refractory AML. Bone Marrow Transplant 46, 636–640 (2011). https://doi.org/10.1038/bmt.2010.181

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