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Conditioning Regimens

Outcomes of patients with AML and MDS who relapse or progress after reduced intensity allogeneic hematopoietic cell transplantation

Abstract

We describe treatment, outcomes and prognostic factors for patients who relapse following transplantation with a reduced intensity conditioning regimen. Seventy consecutive patients with high-risk myeloid malignancies underwent transplant and 25 (36%) relapsed, a median of 120 days later. The median percentage of bone marrow blasts at relapse was 24, the median donor chimerism was 73% and new karyotypic abnormalities occurred in 8 out of 20 (40%) evaluable patients. Twenty-one patients (84%) received aggressive treatment for relapse, including chemotherapy (60%), second hematopoietic cell transplantation (HCT; 52%) and/or donor lymphocyte infusion (DLI; 12%). Thirteen achieved a complete response (CR) and four remain in CR. Median overall survival (OS) after relapse was 6 months (95% confidence interval=2.7–9.9 months), and actuarial 1 year OS was 24%. Most deaths were due to disease progression (17/20, 85%). We did not observe an advantage for cellular therapy (DLI or second transplant) compared to chemotherapy. Salvage therapy for relapse after reduced intensity HCT is feasible, associated with low treatment-related mortality, and may result in prolonged survival in select patients. Studies exploring the optimal treatment for relapse following reduced intensity HCT are warranted.

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References

  1. Mortimer J, Blinder MA, Schulman S, Appelbaum FR, Buckner CD, Clift RA et al. Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy. J Clin Oncol 1989; 7: 50–57.

    Article  CAS  Google Scholar 

  2. Frassoni F, Barrett AJ, Granena A, Ernst P, Garthon G, Kolb HJ et al. Relapse after allogeneic bone marrow transplantation for acute leukaemia: a survey by the E.B.M.T. of 117 cases. Br J Haematol 1988; 70: 317–320.

    Article  CAS  Google Scholar 

  3. Bosi A, Laszlo D, Labopin M, Reffeirs J, Michallet M, Gluckman E et al. Second allogeneic bone marrow transplantation in acute leukemia: results of a survey by the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol 2001; 19: 3675–3684.

    Article  CAS  Google Scholar 

  4. Mehta JPR, Treleaven J, Horton C, Meller S, Pinkerton CR, Singhal S . Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy. Bone Marrow Transplant 1997; 19: 709–719.

    Article  CAS  Google Scholar 

  5. Wagner JE, Vogelsang GB, Zehnbauer BA, Griffin CA, Shah N, Santos GW . Relapse of leukemia after bone marrow transplantation: effect of second myeloablative therapy. Bone Marrow Transplant 1992; 9: 205–209.

    CAS  PubMed  Google Scholar 

  6. Hosing C, Saliba RM, Shahjahan M, Estey EH, Couriel D, Giralt S et al. Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia. Bone Marrow Transplant 2005; 36: 157–162.

    Article  CAS  Google Scholar 

  7. Kishi KTS, Gondo H, Shiobara S, Kanamaru A, Kato S, Hirabayashi N et al. Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes. Bone Marrow Transplant 1997; 19: 461–466.

    Article  CAS  Google Scholar 

  8. Artz AS . Comorbidity and beyond: pre-transplant clinical assessment. Bone Marrow Transplant 2005; 36: 473–474.

    Article  CAS  Google Scholar 

  9. Diaconescu R, Flowers CR, Storer B, Sorror ML, Maris MB, Maloney DG et al. Morbidity and mortality with nonmyeloablative compared with myeloablative conditioning before hematopoietic cell transplantation from HLA-matched related donors. Blood 2004; 104: 1550–1558.

    Article  CAS  Google Scholar 

  10. Sorror ML, Maris MB, Storer B, Sandmaier BM, Diaconescu R, Flowers C et al. Comparing morbidity and mortality of HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative and myeloablative conditioning: influence of pretransplantation comorbidities. Blood 2004; 104: 961–968.

    Article  CAS  Google Scholar 

  11. van Besien K, Artz A, Smith S, Cao D, Rich S, Godley L et al. Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005; 23: 5728–5738.

    Article  CAS  Google Scholar 

  12. Van Besien K, Devine S, Wickrema A, Jessop E, Amin K, Yassine M et al. Regimen-related toxicity after fludarabine-melphalan conditioning: a prospective study of 31 patients with hematologic malignancies. Bone Marrow Transplant 2003; 32: 471–476.

    Article  CAS  Google Scholar 

  13. Michaelis L, Lin S, Joseph L, Artz AS, Kline J, Pollyea D et al. Chimerism does not predict for outcome after alemtuzumab based conditioning. Bone Marrow Transplant 2007; 40: 181.

    Article  CAS  Google Scholar 

  14. StataCorp. Stata Statistical Software, 8.0 edn. Stata Corporation: College Station, TX, 2003.

  15. Herens C, Brasseur E, Jamar M, Vierset L, Schoenen I, Koulischer L . Loss of the Y chromosome in bone marrow cells: results on 1907 consecutive cases of leukaemia and preleukaemia. Clin Lab Haematol 1999; 21: 17–20.

    Article  CAS  Google Scholar 

  16. Giralt S, Escudier S, Kantarjian H, Deisseroth A, Freireich EJ, Andersson BS et al. Preliminary results of treatment with filgrastim for relapse of leukemia and myelodysplasia after allogeneic bone marrow transplantation. N Engl J Med 1993; 329: 757–761.

    Article  CAS  Google Scholar 

  17. Tauro S, Craddock C, Peggs K, Begum G, Mahendra P, Cook G et al. Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia. J Clin Oncol 2005; 23: 9387–9393.

    Article  CAS  Google Scholar 

  18. Mrsic M, Horowitz MM, Atkinson K, Biggs JC, Champlin RE, Ehninger G et al. Second HLA-identical sibling transplants for leukemia recurrence. Bone Marrow Transplant 1992; 9: 269–275.

    CAS  PubMed  Google Scholar 

  19. Kobayashi K, Kami M, Murashige N, Kusumi E, Kishi Y, Hamaki T et al. Outcomes of patients with acute leukaemia who relapsed after reduced-intensity stem cell transplantation from HLA-identical or one antigen-mismatched related donors. Br J Haematol 2005; 129: 795–802.

    Article  Google Scholar 

  20. Radich JP, Gooley T, Sanders JE, Anasetti C, Chauncey T, Appelbaum FR . Second allogeneic transplantation after failure of first autologous transplantation. Biol Blood Marrow Transplant 2000; 6: 272–279.

    Article  CAS  Google Scholar 

  21. Michallet M, Tanguy ML, Socie G, Thiebaut A, Belhabri A, Milpied N et al. Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Societe Francaise de Greffe de Moelle (SFGM). Br J Haematol 2000; 108: 400–407.

    Article  CAS  Google Scholar 

  22. Kottaridis PD, Milligan DW, Chopra R, Chakraverty RK, Chakrabarti S, Robinson S et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation. Blood 2000; 96: 2419–2425.

    CAS  PubMed  Google Scholar 

  23. van Besien K, Artz A, Stock W . Unrelated donor transplantation over the age of 55. Are we merely getting (b)older? Leukemia 2005; 19: 31–33.

    Article  CAS  Google Scholar 

  24. Kumar L . Leukemia: management of relapse after allogeneic bone marrow transplantation. J Clin Oncol 1994; 12: 1710–1717.

    Article  CAS  Google Scholar 

  25. Bethge WA, Storer BE, Maris MB, Flowers ME, Maloney DG, Chauncey TR et al. Relapse or progression after hematopoietic cell transplantation using nonmyeloablative conditioning: effect of interventions on outcome. Exp Hematol 2003; 31: 974–980.

    Article  Google Scholar 

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Pollyea, D., Artz, A., Stock, W. et al. Outcomes of patients with AML and MDS who relapse or progress after reduced intensity allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 40, 1027–1032 (2007). https://doi.org/10.1038/sj.bmt.1705852

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