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Haploidentical vs. mismatched unrelated donor transplants with posttransplant cyclophosphamide-based GVHD prophylaxis

Bone Marrow Transplantation volume 59, pages 1196–1198 (2024)Cite this article

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Post-transplant cyclophosphamide (PTcy) has yielded encouraging results as GVHD prophylaxis in haploidentical transplants [1,2,3]. Given its encouraging activity, PTcy is being increasingly used in mismatched unrelated donor (MMUD) transplants. We along with others have previously shown that MMUD transplant outcomes using PTcy were comparable to conventional GVHD prophylaxis agents [4,5,6,7,8,9,10,11]. With increasing use of haploidentical transplants in the recent years, and emerging data showing promising activity of PTcy in MMUD, we conducted this single institution retrospective study comparing outcomes of haploidentical and MMUD transplants for AML and MDS who received peripheral blood stem cells (PBSC) allografts, and PTcy, tacrolimus, and mycophenolate for GVHD prophylaxis.

Patients with no HLA-matched donors could receive haploidentical or MMUD transplant. Our institution preference is to select donors younger than 40 years. We screen for MMUD while searching for an HLA-matched unrelated donor (MUD) through the NMDP registry. Thus, we could quickly proceed with MMUD in situations when HLA-MUD was unavailable. Myeloablative conditioning (MAC) regimen consisted of busulfan 130 mg/m2 (days −6 to −3) and fludarabine 30 mg/m2 (days −6 to −2) (Bu/Flu). Reduced intensity conditioning (RIC) regimens included [1] busulfan 130 mg/ m2 (days −6 and −5), fludarabine 30 mg/ m2 (days −6 to −2), and TBI 200 cGy (day 0) (Bu/Flu/TBI), and [2] fludarabine 30 mg/ m2 (days −6 to −2), melphalan 140 mg/m2 (day −2), and TBI 200 cGy (day 0) (Flu/Mel/TBI). Busulfan was dosed pharmacokinetically to achieve an AUC of 5000 μmolar × minute for each dose. The primary objective was overall survival (OS) and GVHD-free relapse-free survival (GRFS) between haploidentical and MMUD transplants. Multivariable Cox and subdistribution proportional hazard regression analyses were carried out by propensity score-based covariate adjustment (PSCA) using group as a response variable, and age, Karnofsky performance score, HCT-CI, diagnosis, conditioning regimen, disease status at transplantation, CMV serotype, donor/recipient sex mismatch, and donor age as nine covariates. The Wayne State University Institutional Review Board approved this study. This research work was carried out in accordance with the code of ethics of the Declaration of Helsinki for experiments involving humans.

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Fig. 1: Cumulative incidence and Kaplan-Meier curves.

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Authors and Affiliations

  1. Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    Dipenkumar Modi, Seongho Kim, Maya Shatta, Abhinav Deol, Andrew Kin, Lois Ayash, Voravit Ratanatharathorn & Joseph P. Uberti

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Contributions

DM, SK, and JU designed research; DM, MS collected data; DM, and SK analyzed the data; DM wrote the first draft of the manuscript; DM, SK, MS, AK, AD, LA, VR, and JU reviewed the manuscript and provided their feedback.

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Correspondence to Dipenkumar Modi.

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Competing interests

Dr. Modi receives research funding from Karyophram, Genmab, ADC therapeutics, Genentech. He served in the advisory board for MorphoSys, ADC therapeutics, Genmab, and Seagen and received financial fees. He received fees for speaker bureau for Beigene. Dr. Deol serves as a Consultant/Advisory board for Adicet, Kite/Gilead and Janssen. Other authors have no existing or potential financial conflict of interest to disclose. Dr. Modi serves in the advisory board in the MorphoSys and Seagen. He receives research funding from Genentech, MorphoSys, Genmab, and ADC Therapeutics, and honorarium from AstraZeneca, Beigene, Genmab, ADC therapeutics, and Seagen. Dr. Deol serves as a Consultant/Advisory board for Adicet, Kite/Gilead and Janssen.

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Modi, D., Kim, S., Shatta, M. et al. Haploidentical vs. mismatched unrelated donor transplants with posttransplant cyclophosphamide-based GVHD prophylaxis. Bone Marrow Transplant 59, 1196–1198 (2024). https://doi.org/10.1038/s41409-024-02309-z

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