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Comparison of outcomes following transplantation with T-replete HLA-haploidentical donors using post-transplant cyclophosphamide to matched related and unrelated donors for patients with AML and MDS aged 60 years or older

Abstract

Allografting from HLA-haploidentical donors (HID) is being increasingly utilized worldwide for patients lacking a conventional matched donor. However, its efficacy in older patients with AML and MDS is unclear. We analyzed 127 consecutive allografts for AML/MDS patients aged ≥ 60 years at our center to compare outcomes using HID to those of contemporaneous transplants using matched sibling (MRD) or matched unrelated (MUD) donors. Patient characteristics were similar except HID transplants were more likely in non-white patients and were more commonly performed with reduced intensity conditioning and a marrow graft. For MRD, MUD and HID transplants respectively, 2-year estimates of non-relapse mortality (17, 23, and 9%), relapse (32, 34, and 33%), overall survival (OS) (62, 55, and 67%) and disease-free survival (DFS) (51, 43, and 58%) were not significantly different. Maximum cumulative incidences of grade 2–4 acute GVHD were not different (27, 37, 39%), but incidences of NIH grade moderate to severe (39, 35, 15%, p = 0.028 MUD vs. HID, p = 0.026 MRD vs. HID) and severe chronic GVHD (9, 12, 0%, p = 0.030 MUD vs. HID, p = 0.009 MRD vs. HID) were significantly higher in MRD and MUD than in HID transplants. On multivariable analysis, donor type was not a significant determinant of OS, DFS, TRM, or relapse. However, male gender and high/very high Disease Risk Index (DRI) were associated with significantly higher rates of relapse (HR 1.94, p = 0.047 for male gender, HR 2.48, p = 0.004 for high/very high DRI) and lower OS (HR 1.94, p = 0.018 for male gender, HR 1.80, p = 0.025 for high/very high DRI). HIDs are an acceptable alternative to matched donors in older patients with AML and MDS.

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References

  1. Lubbert M, Suciu S, Baila L, Ruter BH, Platzbecker U, Giagounidis A, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011;29:1987–96.

    Article  Google Scholar 

  2. Walter RB, Kantarjian HM, Huang X, Pierce SA, Sun Z, Gundacker HM, et al. Effect of complete remission and responses less than complete remission on survival in acute myeloid leukemia: a combined Eastern Cooperative Oncology Group, Southwest Oncology Group, and M. D. Anderson Cancer Center Study. J Clin Oncol. 2010;28:1766–71.

    Article  Google Scholar 

  3. Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, et al. Phase II study of allogeneic transplantation for older patients with acute myeloid leukemia in first complete remission using a reduced-intensity conditioning regimen: results from Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015;33:4167–75.

    Article  Google Scholar 

  4. Pohlen M, Groth C, Sauer T, Gorlich D, Mesters R, Schliemann C, et al. Outcome of allogeneic stem cell transplantation for AML and myelodysplastic syndrome in elderly patients (60 years). Bone Marrow Transplant. 2016;51:1441–8.

    Article  CAS  Google Scholar 

  5. Rashidi A, Ebadi M, Colditz GA, DiPersio JF. Outcomes of allogeneic stem cell transplantation in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis. Biol Blood Marrow Transplant. 2016;22:651–7.

    Article  Google Scholar 

  6. Zhang ZH, Lian XY, Yao DM, He PF, Ma JC, Xu ZJ, et al. Reduced intensity conditioning of allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia in patients older than 50 years of age: a systematic review and meta-analysis. J Cancer Res Clin Oncol; e-pub ahead of print 3 May 2017; https://doi.org/10.1007/s00432-017-2429-z.

    Article  Google Scholar 

  7. 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.

    Article  CAS  Google Scholar 

  8. O’Donnell PV, Luznik L, Jones RJ, Vogelsang GB, Leffell MS, Phelps M, et al. Nonmyeloablative bone marrow transplantation from partially HLA-mismatched related donors using posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2002;8:377–86.

    Article  Google Scholar 

  9. Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–50.

    Article  CAS  Google Scholar 

  10. Brunstein CG, Fuchs EJ, Carter SL, Karanes C, Costa LJ, Wu J, et al. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts. Blood. 2011;118:282–8.

    Article  CAS  Google Scholar 

  11. Ciurea SO, Mulanovich V, Saliba RM, Bayraktar UD, Jiang Y, Bassett R, et al. Improved early outcomes using a T cell replete graft compared with T cell depleted haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012;18:1835–44.

    Article  Google Scholar 

  12. Bashey A, Zhang X, Sizemore CA, Manion K, Brown S, Holland HK, et al. T-cell-replete HLA-haploidentical hematopoietic transplantation for hematologic malignancies using post-transplantation cyclophosphamide results in outcomes equivalent to those of contemporaneous HLA-matched related and unrelated donor transplantation. J Clin Oncol. 2013;31:1310–6.

    Article  CAS  Google Scholar 

  13. Raiola AM, Dominietto A, Ghiso A, Di Grazia C, Lamparelli T, Gualandi F, et al. Unmanipulated haploidentical bone marrow transplantation and posttransplantation cyclophosphamide for hematologic malignancies after myeloablative conditioning. Biol Blood Marrow Transplant. 2013;19:117–22.

    Article  CAS  Google Scholar 

  14. Slade M, DiPersio JF, Westervelt P, Vij R, Schroeder MA, Romee R. Haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide and peripheral blood stem cell grafts in older adults with acute myeloid leukemia or myelodysplastic syndrome. Biol Blood Marrow Transplant. 2017;23:1736–43.

    Article  CAS  Google Scholar 

  15. Di Stasi A, Milton DR, Poon LM, Hamdi A, Rondon G, Chen J, et al. Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic syndrome patients with haploidentical versus 10/10 human leukocyte antigen-matched unrelated and related donors. Biol Blood Marrow Transplant. 2014;20:1975–81.

    Article  Google Scholar 

  16. 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  Google Scholar 

  17. Ruggeri A, Peffault de Latour R, Carmagnat M, Clave E, Douay C, Larghero J, et al. Outcomes, infections, and immune reconstitution after double cord blood transplantation in patients with high-risk hematological diseases. Transpl Infect Dis. 2011;13:456–65.

    Article  CAS  Google Scholar 

  18. Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement of the Disease Risk Index for allogeneic stem cell transplantation. Blood. 2014;123:3664–71.

    Article  CAS  Google Scholar 

  19. Klein JP, Rizzo JD, Zhang MJ, Keiding N. Statistical methods for the analysis and presentation of the results of bone marrow transplants. Part I: unadjusted analysis. Bone Marrow Transplant. 2001;28:909–15.

    Article  CAS  Google Scholar 

  20. Bashey A, Zhang MJ, McCurdy SR, St Martin A, Argall T, Anasetti S, et al. Mobilized peripheral blood stem cells versus unstimulated bone marrow as a graft source for T-cell–replete haploidentical donor transplantation using post-transplant cyclophosphamide. J Clin Oncol. 2017;35:3002–9.

    Article  CAS  Google Scholar 

  21. Solh M, Zhang X, Connor K, Brown S, Solomon SR, Morris LE, et al. Post-relapse survival after haploidentical transplantation vs matched-related or matched-unrelated hematopoietic cell transplantation. Bone Marrow Transplant. 2016;51:949–54.

    Article  CAS  Google Scholar 

  22. Estey E, de Lima M, Tibes R, Pierce S, Kantarjian H, Champlin R, et al. Prospective feasibility analysis of reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Blood. 2007;109:1395–400.

    Article  CAS  Google Scholar 

  23. McClune BL, Weisdorf DJ, Pedersen TL, Tunes da Silva G, Tallman MS, Sierra J, et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol. 2010;28:1878–87.

    Article  Google Scholar 

  24. Aoki J, Kanamori H, Tanaka M, Yamasaki S, Fukuda T, Ogawa H, et al. Impact of age on outcomes of allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in elderly patients with acute myeloid leukemia. Am J Hematol. 2016;91:302–7.

    Article  Google Scholar 

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

    Article  Google Scholar 

  26. Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, et al. Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood. 2015;125:3956–62.

    Article  CAS  Google Scholar 

  27. Bashey A, Zhang X, Jackson K, Brown S, Ridgeway M, Solh M, et al. Comparison of outcomes of hematopoietic cell transplants from T-replete haploidentical donors using post-transplantation cyclophosphamide with 10 of 10 HLA-A, -B, -C, -DRB1, and -DQB1 allele-matched unrelated donors and HLA-identical sibling donors: a multivariable analysis including Disease Risk Index. Biol Blood Marrow Transplant. 2016;22:125–33.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  29. Blaise D, Furst 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 unrelated donor. Biol Blood Marrow Transplant. 2016;22:119–24.

    Article  Google Scholar 

  30. Raiola AM, Dominietto A, di Grazia C, Lamparelli T, Gualandi F, Ibatici A, et al. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transplant. 2014;20:1573–9.

    Article  Google Scholar 

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Correspondence to Melhem Solh.

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Bashey, Z.A., Zhang, X., Brown, S. et al. Comparison of outcomes following transplantation with T-replete HLA-haploidentical donors using post-transplant cyclophosphamide to matched related and unrelated donors for patients with AML and MDS aged 60 years or older. Bone Marrow Transplant 53, 756–763 (2018). https://doi.org/10.1038/s41409-018-0126-4

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