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Low incidence of engraftment syndrome following allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide

Bone Marrow Transplantation volume 59, pages 131–133 (2024)Cite this article

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In recent years, graft-versus-host disease (GVHD) prophylaxis involving high-dose post-transplant cyclophosphamide (PTCy) has emerged as a highly effective alternative to the standard regimen of methotrexate (MTX) and a calcineurin inhibitor (CNI). First investigated in the early 2000s among recipients of haploidentical hematopoietic cell transplant (HCT) [1], PTCy has since been studied in recipients of related and unrelated HLA-matched and -mismatched grafts with promising results. For example, in a recent phase III trial (BMT CTN 1703) comparing tacrolimus (Tac)/MTX to PTCy/Tac/mycophenolate mofetil (MMF) after predominantly HLA-matched allogeneic HCT (allo-HCT) with reduced-intensity conditioning (RIC) and peripheral blood stem cell grafts, patients randomized to PTCy/Tac/MMF had significantly higher GVHD-free, relapse-free survival at one year (HR 0.64, p = 0.001), driven principally by a lower incidence of acute and chronic GVHD relative to CNI/MTX [2].

Despite the expanding use of PTCy, important knowledge gaps remain. Among these gaps includes the identification of risk factors and outcomes associated with complications of allo-HCT, including engraftment syndrome (ES). Based on criteria articulated by Spitzer [3], ES occurs in up to one-third of patients receiving allo-HCT with CNI/MTX GVHD prevention and is characterized by the presence of three “major” and four “minor” criteria proximal to neutrophil engraftment. Treatment of ES is generally supportive, although severe cases can require systemic corticosteroids. Importantly, ES has been linked to worse outcomes after allo-HCT, with a recent meta-analysis reporting increased risks of acute GVHD (OR 2.5, p < 0.001), non-relapse mortality (OR 1.9, p = 0.01), and lower overall survival (OR 0.72, p < 0.001) in patients experiencing ES [4]. As prior studies have been limited to allo-HCT patients receiving CNI/MTX, we performed a single-center, retrospective analysis to explore the incidence of ES in patients receiving PTCy-based GVHD prevention.

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Authors and Affiliations

  1. Harvard Medical School, Boston, MA, USA

    Daniel J. Ikeda, Zachariah DeFilipp, Kerry Collier, Yi-Bin Chen, Bimalangshu R. Dey, Areej El-Jawahri, Matthew J. Frigault, Mark B. Leick, Steven L. McAfee, Richard A. Newcomb, Paul V. O’Donnell & Thomas R. Spitzer

  2. Hematopoietic Cell Transplant and Cellular Therapy Program, Massachusetts General Hospital, Boston, MA, USA

    Zachariah DeFilipp, Kerry Collier, Yi-Bin Chen, Bimalangshu R. Dey, Areej El-Jawahri, Matthew J. Frigault, Mark B. Leick, Steven L. McAfee, Richard A. Newcomb, Paul V. O’Donnell & Thomas R. Spitzer

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  1. Daniel J. Ikeda
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Contributions

TRS conceived the idea for the study. DJI and KC collected study data, and DJI performed the statistical analyses. DJI, TRS, and ZD wrote the first draft of the paper. YC, BRD, AE, MJF, MBL, SLM, RAN, and PVO provided critical feedback on the paper, and all authors approved the final version of the paper.

Corresponding author

Correspondence to Thomas R. Spitzer.

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Competing interests

Y-BC: Consulting for Incyte, Takeda, Magenta, Celularity, Novo Nordisk, and Astellas. Matthew JF: Consulting: Kite, Novartis, BMS, Iovance. Research: Arcellx, Novartis, Kite. Richard A. Newcomb: Equity was received from Timedoc in 2022 and 2023; the relationship now ended. Spouse equity received from Vertex Pharmaceuticals; relationship ongoing. Thomas R Spitzer: Bluebird Bio (Data Monitoring Committee), Ossium Health (Scientific Review Committee), Qihan Biotech (Scientific Advisory Board), Syneos Health (Data Monitoring and Adjudication Committees).

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Ikeda, D.J., DeFilipp, Z., Collier, K. et al. Low incidence of engraftment syndrome following allogeneic hematopoietic cell transplantation with post-transplant cyclophosphamide. Bone Marrow Transplant 59, 131–133 (2024). https://doi.org/10.1038/s41409-023-02123-z

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