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Post-transplantation cyclophosphamide for GVHD prophylaxis in severe aplastic anemia

Bone Marrow Transplantation volume 46, pages 1012–1013 (2011)Cite this article

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Acquired severe aplastic anemia (SAA) is a life-threatening hematopoietic stem cell disorder with pancytopenia and a hypocellular BM.1 Allogeneic BMT is the treatment of choice for patients <40 years, who have a human leucocyte antigen (HLA)-matched donor. SAA patients over age 40 with a matched sibling donor and SAA patients of any age without a matched sibling donor are usually treated with immunosuppressive therapy that may include CYA and anti-thymocyte globulin or high dose of cyclophosphamide (CY).2, 3 Unfortunately, 30–50% of SAA patients treated with immunosuppressive therapy, do not respond to treatment, relapse, or develop secondary clonal diseases. For these patients, BMT (BMT) offers the best chance for cure. Patient age and the type of allograft (HLA-matched sibling, unrelated or mismatched donors) are the most important factors influencing the outcome. The risk of GVHD steadily increases with age, leading to reduced survival, especially in patients over the age of 40. TRM approaches 50% in patients over 40-years old.4, 5, 6 Unrelated donors and mismatched transplants have almost twice the TRM and risk of GVHD as matched sibling donor transplants.7 We have previously shown that high-dose CY (50 mg/kg/day) on days 3 and 4 following HLA-matched sibling, unrelated and haplo-identical BMT can facilitate engraftment and mitigate GVHD in hematological malignancies.8, 9 Here, we show that GVHD and rejection can be prevented in SAA patients over the age of 40 with post-transplant CY.

Increasing age has been shown to adversely influence the survival of SAA patients who undergo BMT. In the years 1976–1989, the European Group for Blood and Marrow Transplantation reported an actuarial survival of SAA patients aged <16, 17–40 and >40 of 60, 53 and 27%, respectively.7 In the years 1990–1998, survival improved to 77, 68 and 54%, respectively. Survival is even less for adult SAA patients undergoing unrelated BMT mainly owing to the complications of graft failure and GVHD.10, 11 Thus, novel regimens that reduce the risk of graft failure and GVHD are needed for adult SAA patients who are unresponsive to immunosuppressive therapy. Here, we demonstrate the feasibility and potential efficacy of post-transplantation CY in two patients over 50 years with refractory SAA, who received a BMT from their HLA-identical siblings following our protocol. Clearly, additional experience is required to characterize further efficacy of high dose, post-transplantation CY. We chose BU/CY as the myeloablative preparatory regimen with the rationale that these patients were older, highly pretreated and heavily transfused. It is possible that a non-myeloablative approach would have allowed engraftment; however, we have previously shown high engraftment rates using this BU/CY conditioning regimen in patients with high-risk hematological malignancies.12 Thus, our goal was to maximize the probability of engraftment and minimize the likelihood of GVHD as there is no need for a graft-versus-tumor effect in SAA. Given the high risk of GVHD following BMT in patients >40 years, and the high risk of GVHD in patients receiving a BMT from mismatched or unrelated BMT donors, these data suggest that the addition of post-transplantation CY to traditional immunosuppression deserves consideration as GVHD prophylaxis in SAA patients at high risk for GVHD.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    A E DeZern, R J Jones & R A Brodsky

  2. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    A E DeZern, L Luznik, E J Fuchs, R J Jones & R A Brodsky

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  1. A E DeZern
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  2. L Luznik
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Correspondence to R A Brodsky.

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DeZern, A., Luznik, L., Fuchs, E. et al. Post-transplantation cyclophosphamide for GVHD prophylaxis in severe aplastic anemia. Bone Marrow Transplant 46, 1012–1013 (2011). https://doi.org/10.1038/bmt.2010.213

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