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Transplant outcomes for patients with therapy-related acute myeloid leukemia with prior lymphoid malignancy: an ALWP of EBMT study

Bone Marrow Transplantation volume 55, pages 224–232 (2020)Cite this article

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Abstract

Allogeneic hematopoietic cell transplant (HCT) is a curative therapy for patients with secondary acute myeloid leukemia (sAML), though the impact of conditioning regimens on HCT outcomes for patients with antecedent lymphoid malignancy is largely unknown. This multicenter, retrospective registry study of the ALWP of the EBMT assessed HCT outcomes in this population. In all, 549 patients ≥18 years with sAML following an antecedent lymphoid malignancy treated with first allograft between 2000–2016 were included. Myeloablative (MAC) and reduced intensity conditioning (RIC) was given in 258 (47%) and 291 (53%), respectively. At 2 years, leukemia-free survival (LFS) was 31.7% (95% CI, 27.5–35.9), overall survival (OS) was 37.4% (95% CI, 33–41.8), nonrelapse mortality (NRM) was 28.9% (95% CI, 25–33), and GVHD-free, relapse-free survival (GRFS) was 22.8% (95% CI, 19–26.6). In multivariate analysis, patients receiving RIC regimens had lower risk of NRM (HR: 0.58, CI: 0.40–0.83, p = 0.003), and improved LFS (HR: 0.67, CI: 0.52–0.85, p = 0.001). Patients with prior autologous HCT had inferior LFS (HR: 1.30, CI: 1.01–1.67, p = 0.01). This study demonstrates that sAML patients following prior lymphoid malignancy treated with RIC regimens have a lower risk of NRM and improved LFS, OS, and GFRS. Other variables associated with inferior outcomes include older age, active disease, adverse cytogenetics, and prior auto-HCT.

Highlights

  • Allogeneic HCT can result in long-term survival for patients with t-AML and prior lymphoid malignancies other than MDS/MPN.

  • Myeloablative conditioning regimen was associated with inferior outcome due to higher NRM in these high-risk and heavily treated disease categories.

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References

  1. Sengsayadeth S, Labopin M, Boumendil A, Finke J, Ganser A, Stelljes M, et al. Transplant outcomes for secondary acute myeloid leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study. Biol Blood Marrow Transplant. 2018;24:1406–14.

    Article  PubMed Central  Google Scholar 

  2. Fianchi L, Criscuolo M, Fabiani E, Falconi G, Maraglino AME, Voso MT, et al. Therapy-related myeloid neoplasms: clinical perspectives. Onco Targets Ther. 2018;11:5909–15.

    Article  CAS  PubMed Central  Google Scholar 

  3. Kuykendall A, Duployez N, Boissel N, Lancet JE, Welch JS. Acute myeloid leukemia: the good, the bad, and the ugly. Am Soc Clin Oncol Educ Book. 2018;38:555–73.

  4. Zeichner SB, Arellano ML. Secondary adult acute myeloid leukemia: a review of our evolving understanding of a complex disease process. Curr Treat Options Oncol. 2015;16:37.

    Article  PubMed Central  Google Scholar 

  5. Bhatia S. Therapy-related myelodysplasia and acute myeloid leukemia. Semin Oncol. 2013;40:666–75.

    Article  CAS  PubMed Central  Google Scholar 

  6. Bertoli S, Sterin A, Tavitian S, Oberic L, Ysebaert L, Bouabdallah R, et al. Therapy-related acute myeloid leukemia following treatment of lymphoid malignancies. Oncotarget. 2016;7:85937–47.

    Article  PubMed Central  Google Scholar 

  7. Kotchetkov R, Masih-Khan E, Chu CM, Atenafu EG, Chen C, Kukreti V, et al. Secondary primary malignancies during the lenalidomide-dexamethasone regimen in relapsed/refractory multiple myeloma patients. Cancer Med. 2017;6:3–11.

    Article  CAS  PubMed Central  Google Scholar 

  8. Castillo JJ, Gertz MA. Secondary malignancies in patients with multiple myeloma, Waldenstrom macroglobulinemia and monoclonal gammopathy of undetermined significance. Leuk Lymphoma. 2017;58:773–80.

    Article  CAS  PubMed Central  Google Scholar 

  9. Giralt S, Ballen K, Rizzo D, Bacigalupo A, Horowitz M, Pasquini M, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.

    Article  PubMed Central  Google Scholar 

  10. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15:825–8.

    CAS  Google Scholar 

  11. Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, et al. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–17.

    Article  CAS  Google Scholar 

  12. Ruggeri A, Labopin M, Ciceri F, Mohty M, Nagler A. Definition of GvHD-free, relapse-free survival for registry-based studies: an ALWP-EBMT analysis on patients with AML in remission. Bone Marrow Transplant. 2016;51:610–1.

    Article  CAS  Google Scholar 

  13. Andersen PK, Klein JP, Zhang MJ. Testing for centre effects in multi-centre survival studies: a Monte Carlo comparison of fixed and random effects tests. Stat Med. 1999;18:1489–1500.

    Article  CAS  PubMed Central  Google Scholar 

  14. Sengsayadeth S, Savani BN, Blaise D, Mohty M. Selecting optimal conditioning regimen and stem cell source. Semin Hematol. 2016;2:111–4.

  15. Sengsayadeth S, Savani BN, Blaise D, Malard F, Nagler A, Mohty M. Reduced intensity conditioning allogeneic hematopoietic cell transplantation for adult acute myeloid leukemia in complete remission—a review from the Acute Leukemia Working Party of the EBMT. Haematologica. 2015;100:859–69.

    Article  PubMed Central  Google Scholar 

  16. Sengsayadeth S, Gatwood KS, Boumendil A, Labopin M, Finke J, Ganser A, et al. Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study. Blood Adv. 2018;2:2127–35.

    Article  CAS  PubMed Central  Google Scholar 

  17. Scott BL, Pasquini MC, Logan BR, Wu J, Devine SM, Porter DL, et al. Myeloablative versus reduced-intensity hematopoietic cell transplantation for acute myeloid leukemia and myelodysplastic syndromes. J Clin Oncol. 2017;35:1154–61.

    Article  PubMed Central  Google Scholar 

  18. van Kampen RJ, Canals C, Schouten HC, Nagler A, Thomson KJ, Vernant JP, et al. Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin’s lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry. J Clin Oncol. 2011;29:1342–8.

    Article  Google Scholar 

  19. Vose JM, Bierman PJ, Anderson JR, Kessinger A, Pierson J, Nelson J, et al. Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: clinical course and patient follow-up. Blood. 1992;80:2142–8.

    Article  CAS  Google Scholar 

  20. Rigacci L, Puccini B, Dodero A, Iacopino P, Castagna L, Bramanti S, et al. Allogeneic hematopoietic stem cell transplantation in patients with diffuse large B cell lymphoma relapsed after autologous stem cell transplantation: a GITMO study. Ann Hematol. 2012;91:931–9.

    Article  PubMed Central  Google Scholar 

  21. Baron F, Labopin M, Ruggeri A, Volt F, Mohty M, Blaise D, et al. Cord blood transplantation is associated with good outcomes in secondary acute myeloid leukemia in first remission. J Intern Med. 2018. https://doi.org/10.1111/joim.12870

    Article  CAS  PubMed Central  Google Scholar 

  22. Roloff GW, Griffiths EA. When to obtain genomic data in acute myeloid leukemia (AML) and which mutations matter. Blood Adv. 2018;2:3070–80.

    Article  CAS  PubMed Central  Google Scholar 

  23. Salit RB, Oliver DC, Delaney C, Sorror ML, Milano F. Prognostic value of the hematopoietic cell transplantation comorbidity index for patients undergoing reduced-intensity conditioning cord blood transplantation. Biol Blood Marrow Transplant. 2017;23:654–8.

    Article  PubMed Central  Google Scholar 

  24. Elsawy M, Storer BE, Milano F, Sandmaier BM, Delaney C, Salit RB, et al. Prognostic performance of the augmented hematopoietic cell transplantation-specific comorbidity/age index in recipients of allogeneic hematopoietic stem cell transplantation from alternative graft sources. Biol Blood Marrow Transplant. 2018. https://doi.org/10.1016/j.bbmt.2018.11.030

    Article  PubMed Central  Google Scholar 

  25. Kongtim P, Parmar S, Milton DR, Perez JMR, Rondon G, Chen J, et al. Impact of a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), on allogeneic transplant outcomes in patients with acute myeloid leukemia and myelodysplastic syndrome. Bone Marrow Transplant. 2018. https://doi.org/10.1038/s41409-018-0344-9

    Article  PubMed Central  Google Scholar 

  26. Baron F, Stevens-Kroef M, Kicinski M, Meloni G, Muus P, Marie JP, et al. Impact of induction regimen and of allogeneic hematopoietic cell transplantation on outcome in younger adults patients with acute myeloid leukemia with a monosomal karyotype. Haematologica. 2018. https://doi.org/10.3324/haematol.2018.204826

    Article  PubMed Central  Google Scholar 

  27. Rowe JM. Progress and predictions: AML in 2018. Best Pr Res Clin Haematol. 2018;31:337–40.

    Article  Google Scholar 

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Authors and Affiliations

  1. Vanderbilt University Medical Center, Nashville, TN, USA

    Katie S. Gatwood & Bipin N. Savani

  2. EBMT Paris Study Office/CEREST-TC, Paris, France

    Myriam Labopin & Audrey Mailhol

  3. University of Freiburg Department of Medicine-Hematology, Oncology, Freiburg, Germany

    Jürgen Finke

  4. Department of Hematology—BMT, Hospital St. Louis, Paris, France

    Gerard Socie

  5. Department of Bone Marrow Transplantation, University Hospital, Essen, Germany

    Dietrich Beelen

  6. Hôpital HURIEZ, UAM allo-CSH, CHRU, Lille, France

    Ibrahim Yakoub-Agha

  7. Dept. D’Hématologie, CHU Nantes, Nantes, France

    Patrice Chevallier

  8. Department of Haematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str.1, Hannover, Germany

    Arnold Ganser

  9. Programme de Transplantation & Therapie Cellulaire, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France

    Didier Blaise & Noel Milpied

  10. Techniciens d’Etude Clinique suivi de patients greffes, Nouvel Hopital Civil, Strasbourg, France

    Lioure Bruno

  11. Department of Hematology, Hopital Saint Antoine, Paris, France

    Mohamad Mohty & Arnon Nagler

  12. Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel

    Arnon Nagler

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  1. Katie S. Gatwood
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Correspondence to Katie S. Gatwood.

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Gatwood, K.S., Labopin, M., Savani, B.N. et al. Transplant outcomes for patients with therapy-related acute myeloid leukemia with prior lymphoid malignancy: an ALWP of EBMT study. Bone Marrow Transplant 55, 224–232 (2020). https://doi.org/10.1038/s41409-019-0673-3

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