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Incorporation of posttransplant cyclophosphamide as part of standard immunoprophylaxis for all allogeneic transplants: a retrospective, single institution study

Bone Marrow Transplantation volume 56, pages 1099–1105 (2021)Cite this article

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Abstract

The addition of posttransplant cyclophosphamide (PTCy) to standard graft-versus-host disease (GVHD) prophylaxis following haploidentical blood stem transplants has resulted in relatively low rates of GVHD. As GVHD remains a major cause of morbidity and mortality in patients receiving transplants from matched donors, we began to use PTCy in all blood stem cell transplants in 2016 and compared our recent experience with PTCy after matched sibling and unrelated donor transplants (N = 49) to the earlier 2-year period (N = 41) when PTCy was not used. Endpoints included graft-versus-host, relapse-free-survival (GRFS), overall survival, non-relapse mortality, and percentage of patients disease-free and off immunosuppression (DFOI) at 1 year and at the last follow-up. The difference in GRFS between the standard and the PTCy cohort was not statistically significant. There was a statistically improved relapse-free and overall survival in the PTCY cohort that was due to a significant decrease in non-relapse mortality secondary to GVHD. There was also a borderline statistically improved DFOI at 1 year and at last follow-up in the PTCY group. These results suggest that PTCy after HLA-matched transplants provides at least comparable efficacy to other GVHD strategies and may allow more frequent discontinuation of immunosuppression.

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Fig. 1: Stacked plots of the different components of GRFS.
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References

  1. 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  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ghosh N, Karmali R, Rocha V, Ahn KW, DiGilio A, Hari PN, et al. Reduced-Intensity transplantation for lymphomas using haploidentical related donors versus HLA-matched sibling donors: a Center for International Blood and Marrow Transplant Research Analysis. J Clin Oncol. 2016;34:3141–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kanate AS, Mussetti A, Kharfan-Dabaja MA, Ahn KW, DiGilio A, Beitinjaneh A, et al. Reduced-intensity transplantation for lymphomas using haploidentical related donors vs HLA-matched unrelated donors. Blood. 2016;127:938–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Solomon SR, Sizemore CA, Sanacore M, Zhang X, Brown S, Holland HK, et al. Haploidentical transplantation using T cell replete peripheral blood stem cells and myeloablative conditioning in patients with high-risk hematologic malignancies who lack conventional donors is well tolerated and produces excellent relapse-free survival: results of a prospective phase II trial. Biol Blood Marrow Transplant. 2012;18:1859–66.

    Article  PubMed  Google Scholar 

  6. Gagelmann N, Bacigalupo A, Rambaldi A, Hoelzer D, Halter J, Sanz J, et al. Haploidentical stem cell transplantation with posttransplant cyclophosphamide therapy vs other donor transplantations in adults with hematologic cancers: a systematic review and meta-analysis. JAMA Oncol. 2019;5:1739–48.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bolanos-Meade J, Reshef R, Fraser R, Fei M, Abhyankar S, Al-Kadhimi Z, et al. Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease with haemopoietic cell transplantation with reduced-intensity conditioning: a randomised phase 2 trial with a non-randomised contemporaneous control group (BMT CTN 1203). Lancet Haematol. 2019;6:e132–e43.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Carnevale-Schianca F, Caravelli D, Gallo S, Coha V, D’Ambrosio L, Vassallo E, et al. Post-transplant cyclophosphamide and tacrolimus-mycophenolate mofetil combination prevents graft-versus-host disease in allogeneic peripheral blood hematopoietic cell transplantation from HLA-matched donors. Biol Blood Marrow Transplant. 2017;23:459–66.

    Article  CAS  PubMed  Google Scholar 

  9. De Jong CN, Meijer E, Bakunina K, van Marwijk Kooij M, de Groot MR, van Gelder M, et al. Post-transplantation cyclophosphamide after allogeneic hematopoietic stem cell transplantation: results of the prospective randomized HOVON-96 trial in recipients of matched related and unrelated donors (abstract). Blood. 2019;134:1.

    Article  Google Scholar 

  10. Garcia-Cadenas I, Awol R, Esquirol A, Saavedra S, Bosch-Vilaseca A, Novelli S, et al. Incorporating posttransplant cyclophosphamide-based prophylaxis as standard-of-care outside the haploidentical setting: challenges and review of the literature. Bone Marrow Transplant. 2020;55:1041–9.

    Article  CAS  PubMed  Google Scholar 

  11. Kanakry CG, Bolanos-Meade J, Kasamon YL, Zahurak M, Durakovic N, Furlong T, et al. Low immunosuppressive burden after HLA-matched related or unrelated BMT using posttransplantation cyclophosphamide. Blood. 2017;129:1389–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Shah MV, Saliba RM, Rondon G, Chen J, Soebbing D, Rus I, et al. Pilot study using post-transplant cyclophosphamide (PTCy), tacrolimus and mycophenolate GVHD prophylaxis for older patients receiving 10/10 HLA-matched unrelated donor hematopoietic stem cell transplantation. Bone Marrow Transplant. 2019;54:601–6.

    Article  CAS  PubMed  Google Scholar 

  14. Holtan SG, DeFor TE, Lazaryan A, Bejanyan N, Arora M, Brunstein CG, et al. Composite end point of graft-versus-host disease-free, relapse-free survival after allogeneic hematopoietic cell transplantation. Blood. 2015;125:1333–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  16. 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  PubMed  PubMed Central  Google Scholar 

  17. Pasquini MC, Logan B, Jones RJ, Alousi AM, Appelbaum FR, Bolanos-Meade J, et al. Blood and marrow transplant clinical trials network report on the development of novel endpoints and selection of promising approaches for graft-versus-host disease prevention trials. Biol Blood Marrow Transplant. 2018;24:1274–80.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc. 1999;94:496–509.

    Article  Google Scholar 

  19. de Lima M, Couriel D, Thall PF, Wang X, Madden T, Jones R, et al. Once-daily intravenous busulfan and fludarabine: clinical and pharmacokinetic results of a myeloablative, reduced-toxicity conditioning regimen for allogeneic stem cell transplantation in AML and MDS. Blood. 2004;104:857–64.

    Article  PubMed  Google Scholar 

  20. Martin PJ. Study design and endpoints in graft-versus-host disease. Best Pract Res Clin Haematol. 2008;21:357–72.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sandmaier BM, Kornblit B, Storer BE, Olesen G, Maris MB, Langston AA, et al. Addition of sirolimus to standard cyclosporine plus mycophenolate mofetil-based graft-versus-host disease prophylaxis for patients after unrelated non-myeloablative haemopoietic stem cell transplantation: a multicentre, randomised, phase 3 trial. Lancet Haematol. 2019;6:e409–18.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Bacigalupo A. ATG in allogeneic stem cell transplantation: standard of care in 2017? Point. Blood Adv. 2017;1:569–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Kekre N, Antin JH. ATG in allogeneic stem cell transplantation: standard of care in 2017? Counterpoint. Blood Adv. 2017;1:573–6.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Walker I, Panzarella T, Couban S, Couture F, Devins G, Elemary M, et al. Addition of anti-thymocyte globulin to standard graft-versus-host disease prophylaxis versus standard treatment alone in patients with haematological malignancies undergoing transplantation from unrelated donors: final analysis of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2020;7:e100–11.

    Article  PubMed  Google Scholar 

  25. Battipaglia G, Labopin M, Kroger N, Vitek A, Afanasyev B, Hilgendorf I, et al. Posttransplant cyclophosphamide vs antithymocyte globulin in HLA-mismatched unrelated donor transplantation. Blood 2019;134:892–9.

    Article  CAS  PubMed  Google Scholar 

  26. Jorge AS, Suarez-Lledo M, Pereira A, Gutierrez G, Fernandez-Aviles F, Rosinol L, et al. Single antigen-mismatched unrelated hematopoietic stem cell transplantation using high-dose post-transplantation cyclophosphamide is a suitable alternative for patients lacking HLA-matched donors. Biol Blood Marrow Transplant. 2018;24:1196–202.

    Article  CAS  PubMed  Google Scholar 

  27. Mehta RS, Saliba RM, Chen J, Rondon G, Hammerstrom AE, Alousi A, et al. Post-transplantation cyclophosphamide versus conventional graft-versus-host disease prophylaxis in mismatched unrelated donor haematopoietic cell transplantation. Br J Haematol. 2016;173:444–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Moiseev IS, Pirogova OV, Alyanski AL, Babenko EV, Gindina TL, Darskaya EI, et al. Graft-versus-host disease prophylaxis in unrelated peripheral blood stem cell transplantation with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Biol Blood Marrow Transplant. 2016;22:1037–42.

    Article  CAS  PubMed  Google Scholar 

  29. Hammerstrom AE, Lombardi LR, Pingali SR, Rondon G, Chen J, Milton DR, et al. Prevention of cytomegalovirus reactivation in haploidentical stem cell transplantation. Biol Blood Marrow Transplant. 2018;24:353–8.

    Article  CAS  PubMed  Google Scholar 

  30. Marty FM, Ljungman P, Chemaly RF, Maertens J, Dadwal SS, Duarte RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377:2433–44.

    Article  CAS  PubMed  Google Scholar 

  31. Lin A, Maloy M, Su Y, Bhatt V, DeRespiris L, Griffin M, et al. Letermovir for primary and secondary cytomegalovirus prevention in allogeneic hematopoietic cell transplant recipients: real-world experience. Transpl Infect Dis 2019;21:e13187.

    CAS  PubMed  Google Scholar 

  32. Sharma P, Gakhar N, MacDonald J, Abidi MZ, Benamu E, Bajrovic V, et al. Letermovir prophylaxis through day 100 post transplant is safe and effective compared with alternative CMV prophylaxis strategies following adult cord blood and haploidentical cord blood transplantation. Bone Marrow Transplant. 2020;55:780–6.

    Article  CAS  PubMed  Google Scholar 

  33. Milano F, Gooley T, Wood B, Woolfrey A, Flowers ME, Doney K, et al. Cord-blood transplantation in patients with minimal residual disease. N Engl J Med. 2016;375:944–53.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Gagelmann N, Ditschkowski M, Bogdanov R, Bredin S, Robin M, Cassinat B, et al. Comprehensive clinical-molecular transplant scoring system for myelofibrosis undergoing stem cell transplantation. Blood. 2019;133:2233–42.

    Article  CAS  PubMed  Google Scholar 

  35. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374:2209–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA

    Dennis L. Cooper, Jacqueline Manago, Vimal Patel, Dale Schaar, Tracy Krimmel, Mary Kate McGrath, Anne Tyno, Yong Lin & Roger Strair

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  1. Dennis L. Cooper
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Cooper, D.L., Manago, J., Patel, V. et al. Incorporation of posttransplant cyclophosphamide as part of standard immunoprophylaxis for all allogeneic transplants: a retrospective, single institution study. Bone Marrow Transplant 56, 1099–1105 (2021). https://doi.org/10.1038/s41409-020-01144-2

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