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Severity and organ distribution of chronic graft-versus-host disease with posttransplant cyclophosphamide-based versus methotrexate/calcineurin inhibitor-based allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 59, pages 373–379 (2024)Cite this article

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Abstract

The reduced risk of chronic graft-versus-host-disease (GVHD) with posttransplant cyclophosphamide (ptCy) in the setting of haploidentical related donor and more recently, with HLA-matched related and matched and mismatched unrelated donor allogeneic transplantation has been established. There is, however, paucity of data to show if ptCy impacts chronic GVHD pathogenesis, its phenotype and evolution after HCT regardless of the donor status. We examined the differences in chronic GVHD incidence and presentation in 314 consecutive patients after receiving their first allogeneic transplantation (HCT) using ptCy-based GVHD prophylaxis (ptCy-HCT; n = 120; including 95 with haploidentical related donor) versus conventional calcineurin inhibitor-based prophylaxis (CNI-MUD; n = 194) between 2012 and 2019. The 1-year cumulative incidence of all-grade chronic GVHD and moderate/severe chronic GVHD was 24% and 12%, respectively, after ptCy-HCT and 40% and 23% in the CNI-MUD recipients (p = 0.0003 and 0.007). Multivariable analysis confirmed that use of CNI-based GVHD prophylaxis and peripheral blood stem cell graft as the risk factors for chronic GVHD. The cumulative incidence of visceral (involving ≥1 of the following organs: liver, lungs, gastrointestinal tract, serous membranes) chronic GVHD was significantly higher with CNI-MUD vs. ptCy-HCT (27% vs. 15% at 1 year, p = 0.009). The incidence of moderate/severe visceral chronic GVHD was 20% in CNI-MUD group vs. 7.7% in the ptCy-HCT group at 1 year (p = 0.002). In addition, significantly fewer ptCy-HCT recipients developed severe chronic GVHD in ≥3 organs (0.8%) vs. 8.8% in the CNI-MUD group at 1-year posttransplant (p = 0.004). There was no significant different in relapse, non-relapse mortality, and relapse-free and overall survival between the two groups. Further investigation is needed to confirm that reduced risk and severity of chronic GVHD, less visceral organ distribution with ptCy-HCT leads to improved quality of life.

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Fig. 1: Chronic GVHD.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Author information

Author notes

  1. Saurabh Chhabra & James H. Jerkins

    Present address: Previously at Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

  2. These authors contributed equally: Saurabh Chhabra, James H. Jerkins.

Authors and Affiliations

  1. Division of Hematology/Oncology, Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ, USA

    Saurabh Chhabra

  2. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    James H. Jerkins

  3. Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Kathleen Monahan, Nirav N. Shah, Sameem Abedin, Lyndsey Runaas, Timothy S. Fenske, Marcelo C. Pasquini, Bronwen E. Shaw, William R. Drobyski, Wael Saber, Anita D’Souza, Binod Dhakal, Meera Mohan, Walter Longo & Mehdi Hamadani

  4. Division of Biostatistics, Institute for Health & Equity Medical College of Wisconsin, Milwaukee, WI, USA

    Aniko Szabo

  5. Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA

    Marcelo C. Pasquini, Bronwen E. Shaw, Wael Saber & Mehdi Hamadani

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Contributions

SC, JJ, AS, and MH designed the study. KM and JJ acquired the data. SC, JJ, KM, AS, and MH analyzed and interpreted the data. SC and JJ drafted the manuscript. All authors reviewed, critically revised and approved the final manuscript. SC and JJ contributed equally as primary co-authors of the manuscript.

Corresponding author

Correspondence to Mehdi Hamadani.

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Competing interests

SC: Honorarium from Janssen, Sanofi, GSK, and institutional research funding from Janssen, Takda, C4 Therapeutics, Abbvie. JHJ: Honorarium from Omeros. SA: Research Funding from Incyte, AltruBio, Actinium Pharmaceutical; Consultancy/Honoraria from AbbVie, Daichii Sankyo, Servier. NNS: Participation on advisory boards and/or consultancy for Kite Pharma, BMS-Juno, Miltenyi Biotec, Lilly Oncology, Epizyme, Incyte, Novartis, Seattle Genetics, Abbvie, and Gallapagos; Research funding, travel support, and honoraria from Lilly Oncology and Miltenyi Biotec; Scientific advisory board for Tundra Therapeutics. TSF: Consultancy, Speakers Bureau: Beigene, Kite (Gilead), Servier Pharmaceuticals, MorphoSys, TG Therapeutics, SeaGen, Adaptive Biotechnologies, Astrazeneca, Pharmacyclics (AbbVie), Sanofi. MCP: Research Funding: Novartis, Bristol Myers Squibb, Kite, a Gilead Company, Janssen; Consultancy: Bristol Myers Squibb; Honoraria: Kite, a Gilead Company, Kite Brazil. BES: Institutional payments from Mallinkrodt, Orcabio. AD: Membership on an entity’s Board of Directors or advisory committees: Imbrium, Pfizer; Consultancy: Bristol Myers Squibb; Janssen, Prothena; Research Funding: Abbvie, Sanofi, Takeda, TeneoBio, Caelum, Prothena. MM: Honoraria: MashupMD, Blood Cancer Today, MJH life sciences, Bristol-Myers Squibb Company; Consultancy: Sanofi S.A; Research Funding: Sanofi. S.A, Amgen Inc, Institutional KL2 Award, Celgene Corporation, Ionis Pharmaceuticals, Takeda Pharmaceutical Company, GlaxoSmithKline plc, Novartis. MH: Research Support/Funding: ADC Therapeutics; Spectrum Pharmaceuticals; Astellas Pharma. Consultancy: ADC Therapeutics, Omeros, CRISPR, BMS, Kite, Abbvie, Caribou, Genmab. Speaker’s Bureau: Sanofi Genzyme., ADC Therapeutics, AstraZeneca, BeiGene, Kite. DMC: Inc, Genentech, Myeloid Therapeutics, CRISPR. All other authors report no relevant conflicts of interest.

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Chhabra, S., Jerkins, J.H., Monahan, K. et al. Severity and organ distribution of chronic graft-versus-host disease with posttransplant cyclophosphamide-based versus methotrexate/calcineurin inhibitor-based allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 59, 373–379 (2024). https://doi.org/10.1038/s41409-023-02178-y

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