Stem cell transplantation

Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT

Abstract

Unmanipulated haploidentical allogeneic stem cell transplantation (Allo-SCT) has become an attractive alternative for patients lacking HLA-matched sibling or unrelated donors. However, data of outcome in ALL is still scarce. The outcomes of 1234 adult patients with ALL in first complete remission (CR1) who underwent Allo-SCT between 2007 and 2016 were analyzed. Comparison was done between haploidentical donor (Haplo) (136 patients), matched unrelated donor (MUD 10/10) (809 patients), and mismatched unrelated donor (MMUD 9/10) (289 patients). Univariate analysis showed similar outcomes in Haplo, MUD, and MMUD, including OS, LFS, RI, NRM, AGVHD, and CGVHD. In multivariate analysis, Haplo was not associated with worse outcomes compared to MUD 10/10 and MMUD 9/10. Indeed, compared to Haplo, the hazard ratio (HR) for LFS, OS, RI, NRM, AGVHD, and CGVHD were 1.1 (p = 0.7), 0.9 (p = 0.4), 1.35 (p = 0.2), 0.7 (p = 0.2), 1.1 (p = 0.8), and 0.8 (p = 0.2) for MUD, respectively, and 1.1 (p = 0.8), 1.0 (p = 1.0), 1.2 (p = 0.3), 0.8 (p = 0.4), 1.2 (p = 0.3), and 0.9 (p = 0.6) for MMUD, respectively. In conclusion, outcomes of adult patients with ALL in CR1 receiving Haplo Allo-SCT are comparable to MUD or MMUD transplants. Haplo should be considered as a clinically relevant option for patients lacking a matched sibling donor.

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References

  1. 1.

    Pui C-H, Evans WE. Treatment of acute lymphoblastic leukemia. N Engl J Med. 2006;354(Jan):166–78.

  2. 2.

    Gökbuget N, Stanze D, Beck J, Diedrich H, Horst HA, Hüttmann A, et al. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012;371:339–48.

  3. 3.

    Thomas X, Boiron JM, Huguet F, Dombret H, Bradstock K, Vey N, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 Trial. J Clin Oncol. 2004;22:4075–86.

  4. 4.

    Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK, et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation. Blood. 2008;111:1827–33.

  5. 5.

    Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371:339–48.

  6. 6.

    Ciurea SO, Bayraktar UD. “No donor”? Consider a haploidentical transplant. Blood Rev. 2015;29:63–70.

  7. 7.

    Tucunduva L, Ruggeri A, Sanz G, Furst S, Socié G, Michallet M, et al. Risk factors for outcomes after unrelated cord blood transplantation for adults with acute lymphoblastic leukemia: a report on behalf of eurocord and the acute leukemia working party of the european group for blood and marrow transplantation. Bone Marrow Transplant. 2014;49:887–94.

  8. 8.

    Ruggeri A, Labopin M, Sanz G, Piemontese S, Arcese W, Bacigalupo A, et al. Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia. Leukemia. 2015;29:1891–900.

  9. 9.

    Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S, Dreger P, et al. Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants. Bone Marrow Transplant. 2015;50:476–82.

  10. 10.

    Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2015;13:10–24.

  11. 11.

    Luznik L, O’Donnell PV, Fuchs EJ. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Semin Oncol. 2012;39:683–93.

  12. 12.

    Liu JH, Kanakry CG, Luznik L. Have haploidentical transplants replaced umbilical cord transplants for acute leukemias? Curr Opin Hematol. 2018;25:103–11.

  13. 13.

    Savani BN, Labopin M, Kröger N, Finke J, Ehninger G, Niederwieser D, et al. Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the acute leukemia working party of the EBMT. Haematologica. 2016;101:773–80.

  14. 14.

    Piemontese S, Ciceri F, Labopin M, Arcese W, Kyrcz-Krzemien S, Santarone S, et al. A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia. J Hematol Oncol. 2017;10:24–9.

  15. 15.

    Ciurea SO, Zhang MJ, Bacigalupo AA, Bashey A, Appelbaum FR, Aljitawi OS, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126:1033–40.

  16. 16.

    Srour SA, Milton DR, Bashey A, Karduss-Urueta A, Al Malki MM, Romee R, et al. Haploidentical transplantation with post-transplantation cyclophosphamide for high-risk acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2017;23:318–24.

  17. 17.

    Chen H, Liu KY, Xu LP, Chen YH, Han W, Zhang X., et al. Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2015;21:1110–6.

  18. 18.

    Gu B, Wu X, Chen G, Ma X, Jin Z, Tang X, et al. Haploidentical allogeneic hematopoietic stem cell transplantation compared to matched unrelated transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Leuk Res. 2017;59:41–6.

  19. 19.

    Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, et al. Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009;15:1628–33.

  20. 20.

    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.

  21. 21.

    Lee SJ, Vogelsang G, Flowers MED. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9:215–33.

  22. 22.

    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.

  23. 23.

    Sureda A, Bader P, Cesaro S, Dreger P, Duarte RF, Dufour C, et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant. 2015;50:1037–56.

  24. 24.

    Gupta V, Richards S, Rowe J. Allogeneic, but not autologous, hematopoietic cell transplantation improves survival only among younger adults with acute lymphoblastic leukemia in first remission: an individual patient data meta-analysis. Blood. 2013;121:339–50.

  25. 25.

    Oliansky DM, Camitta B, Gaynon P, Nieder ML, Parsons SK, Pulsipher MA, et al. Role of cytotoxic therapy with hematopoietic stem cell transplantation in the treatment of pediatric acute lymphoblastic leukemia: update of the 2005 evidence-based review. Biol Blood Marrow Transplant. 2012;18:18–36.

  26. 26.

    Messori A, Fadda V, Maratea D, Trippoli S. Acute lymphoblastic leukemia in first complete remission: temporal trend of outcomes in studies comparing allogeneic transplant with autologous transplant or chemotherapy. Ann Hematol. 2013;92:1221–8.

  27. 27.

    Versluis J, Labopin M, Ruggeri A, Socie G, Wu D, Volin L, et al. Alternative donors for allogeneic hematopoietic stem cell transplantation in poor-risk AML in CR1. Blood Adv. 2017;1:477–85.

  28. 28.

    Blaise D, Fürst S, Crocchiolo R, El-Cheikh J, Granata A, Harbi S, et al. Haploidentical T cell-replete transplantation with post-transplantation cyclophosphamide for patients in or above the sixth decade of age compared with allogeneic hematopoietic stem cell transplantation from an human leukocyte antigen-matched related or U. Biol Blood Marrow Transplant. 2016;22:119–24.

  29. 29.

    Santoro N, Ruggeri A, Labopin M, Bacigalupo A, Ciceri F, Gülbaş Z, et al. Unmanipulated haploidentical stem cell transplantation in adults with acute lymphoblastic leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT. J Hematol Oncol. 2017;10:113–23.

  30. 30.

    Bashey A, Zhang M, McCurdy SR, Ciurea SO, St. Martin A, Anasetti C, et al. Comparison of peripheral blood stem cells (PBSC) to bone marrow (BM) for T-replete HLA-haploidentical donor transplantation using post-transplant cyclophosphamide. Blood. 2016;128:683.

  31. 31.

    Ruggeri A, Labopin M, Bacigalupo A, Gülbas Z, Koc Y, Blaise D, et al. Use of bone marrow or peripheral blood stem cell grafts in non T cell depleted haploidentical transplants using post-transplant cyclophosphamide, an ALWP-EBMT analysis. Blood. 2016;128:1165.

  32. 32.

    Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, et al. Haploidentical versus matched-sibling transplant in adults with philadelphia-negative high-risk acute lymphoblastic leukemia: a biologically phase III randomized study. Clin Cancer Res. 2016;22:3467–76.

  33. 33.

    Ruggeri A, Sun Y, Labopin M, Bacigalupo A, Lorentino F, Arcese W, et al. Post-transplant cyclophosphamide versus antithymocyte-globulin as graft versus host disease prophylaxis in haploidentical transplant. Haematologica. 2017;102:401–10.

  34. 34.

    Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen JJ, Elmaagacli A, et al. Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol. 2018;11:40–6.

  35. 35.

    Ruutu T, Gratwohl A, De Witte T, Afanasyev B, Apperley J, Bacigalupo A, et al. Prophylaxis and treatment of GVHD: EBMT–ELN working group recommendations for a standardized practice. Bone Marrow Transplant. 2013;49:168–73.

  36. 36.

    Giebel S, Czyz A, Ottmann O, Baron F, Brissot E, Ciceri F, et al. Use of tyrosine kinase inhibitors to prevent relapse after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: a position statement of the acute leukemia working party of the European Society for Blood and Marrow Transplantation. Cancer. 2016;122:2941–51.

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Correspondence to Noga Shem-Tov.

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Shem-Tov, N., Peczynski, C., Labopin, M. et al. Haploidentical vs. unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia in first complete remission: on behalf of the ALWP of the EBMT. Leukemia 34, 283–292 (2020) doi:10.1038/s41375-019-0544-3

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