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. 2018 Mar 15;11(1):40.
doi: 10.1186/s13045-018-0586-4.

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

Annalisa Ruggeri  1   2 , Myriam Labopin  3   4 , Andrea Bacigalupo  5 , Boris Afanasyev  6 , Jan J Cornelissen  7 , Ahmet Elmaagacli  8 , Maija Itälä-Remes  9 , Didier Blaise  10 , Ellen Meijer  11 , Yener Koc  12 , Noel Milpied  13 , Harry C Schouten  14 , Nicolaus Kroeger  15 , Mohamad Mohty  3   4   16 , Arnon Nagler  16   17
Affiliations

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

Annalisa Ruggeri et al. J Hematol Oncol. .

Abstract

Background: Experience using post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis in allogeneic stem cell transplantation (HSCT) from matched sibling donors (MSD) or unrelated donors (UD) is limited and with controversial results. The study aim was to evaluate PT-Cy as GVHD prophylaxis post-HSCT from MSD and UD transplants. We analyzed 423 patients with acute leukemia who received PT-Cy alone or in combination with other immunosuppressive (IS) drugs as GVHD prophylaxis. Seventy-eight patients received PT-Cy alone (group 1); 204 received PT-Cy in combination with one IS drug-cyclosporine-A (CSA) or methotrexate (MTX) or mycophenolate-mofetil (MMF) (group 2), while 141 patients received PT-Cy in combination with two IS drugs-CSA + MTX or CSA + MMF (group 3). Transplants were performed from 2007 to 2015 and median follow-up was 20 months.

Results: Probability of overall survival (OS) at 2 years was 50, 52.2, and 62.4%, for the three groups, respectively, p = 0.06. In multivariate analysis, in comparison to PT-Cy alone, the addition of two IS drugs was associated with reduced risk of extensive cGVHD (HR 0.25, p = 0.02). Use of bone marrow (BM) and anti-thymocyte globulin were independently associated with reduced risk of extensive cGVHD. Prognostic factors for non-relapse mortality (NRM) were the addition of two IS drugs to PT-Cy (HR 0.35, p = 0.04), diagnosis of AML, disease status at transplant, and patient CMV serology. Factors associated with increased OS were the use of PT-Cy with two IS drugs (HR 0.49, p = 0.02), AML, and disease status at transplant.

Conclusion: For GVHD prophylaxis in MSD and UD HSCT, the addition of IS drugs to PT-Cy enhances its effect and reduces the risk of severe cGVHD, reducing mortality and improving survival.

Keywords: Acute graft-versus-host disease; Acute leukemia; Hematopoietic stem cell transplantation; Post-transplantation cyclophosphamide; Stem cell source.

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Conflict of interest statement

Ethics approval and consent to participate

The scientific boards of the ALWP of EBMT approved this study. All patients gave written informed consent for the use of their data.

Consent for publication

Not applicable for individual patient data. This is a pooled analysis.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
a cGVHD, b extensive cGVHD, and c GRFS by GVHD prophylaxis strategy
Fig. 2
Fig. 2
a RI, b NRM, c LFS, and d OS by GVHD prophylaxis strategy
See this image and copyright information in PMC

References

    1. Boyiadzis M, Arora M, Klein JP, Hassebroek A, Hemmer M, Urbano-Ispizua A, Antin JH, Bolwell BJ, Cahn JY, Cairo MS, et al. Impact of chronic graft-versus-host disease on late relapse and survival on 7,489 patients after myeloablative allogeneic hematopoietic cell transplantation for leukemia. Clin Cancer Res. 2015;21:2020–2028. doi: 10.1158/1078-0432.CCR-14-0586. - DOI - PMC - PubMed
    1. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, Martin PJ, Sandmaier BM, Marr KA, Appelbaum FR, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363:2091–2101. doi: 10.1056/NEJMoa1004383. - DOI - PMC - PubMed
    1. Nash RA, Antin JH, Karanes C, Fay JW, Avalos BR, Yeager AM, Przepiorka D, Davies S, Petersen FB, Bartels P, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000;96:2062–2068. - PubMed
    1. Bolwell B, Sobecks R, Pohlman B, Andresen S, Rybicki L, Kuczkowski E, Kalaycio M. A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation. Bone Marrow Transplant. 2004;34:621–625. doi: 10.1038/sj.bmt.1704647. - DOI - PubMed
    1. Jagasia M, Arora M, Flowers ME, Chao NJ, McCarthy PL, Cutler CS, Urbano-Ispizua A, Pavletic SZ, Haagenson MD, Zhang MJ, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012;119:296–307. doi: 10.1182/blood-2011-06-364265. - DOI - PMC - PubMed

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