Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis After Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: PURPOSE: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for advanced hematologic malignancies. HSCT using human leukocyte antigen (HLA)-mismatched donors is historically associated with inferior survival. Patients from underrepresented racial and ethnic groups more frequently rely on HLA-mismatched donors. We hypothesized that post-transplant cyclophosphamide (PTCy) based graft versus host disease (GVHD) prophylaxis would improve outcomes for HSCT recipients using peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors (MMUDs) by reducing the risk of GVHD. METHODS: This phase II, nonrandomized, multicenter trial assessed PBSCs in the setting of a GVHD prophylaxis regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil in two adult strata: myeloablative conditioning (MAC) and reduced-intensity or nonmyeloablative (RIC/NMA) conditioning before HSCT from a MMUD. The primary objective was to estimate 1 year overall survival (OS) for each stratum. Key secondary end points included incidences of acute and chronic GVHD. RESULTS: A total of 145 patients enrolled, with 59% self-identifying within an underrepresented group. The 1 year OS was 83.8% (95% CI, 73.1% to 90.4%) for MAC and 78.6% (95% CI, 67% to 86.5%) for RIC/NMA. Incidences of grades III to IV acute GVHD at 6 months were 8% (95% CI, 3.2 to 15.6) for MAC and 10% (95% CI, 4.4 to 18.4) for RIC/NMA. Moderate/severe chronic GVHD at 1 year was 10.3% (95% CI, 4.4 to 18.9) for MAC and 8.6% (95% CI, 3.5 to 16.6) for RIC/NMA. 32% of patients whose donors matched at fewer than seven of eight HLA alleles had similar OS compared with those with donor matched at seven of eight alleles. CONCLUSION: PTCy-based GVHD prophylaxis after MMUD HSCT with PBSC grafts results in favorable 1 year OS. Using MMUDs expands donor availability to all patients regardless of ancestry (ACCESS; ClinicalTrials.gov identifier: NCT04904588).
Source: Journal of Clinical Oncology
DOI: 10.1200/jco-25-00856
Authors: Monzr M. Al Malki, Stephanie Bo-Subait, Brent Logan, Janelle Olson, Jianqun Kou, Sarah Smith, Erin Leckrone, Juan Wu, Heather E. Stefanski, Jeffery J. Auletta, Stephen R. Spellman, Craig Malmberg, Medhat Askar, Rachel Cusatis, Brian C. Shaffer, Dipenkumar Modi, Farhad Khimani, Mahasweta Gooptu, Mehdi Hamadani, Abeer Madbouly, Martin Maiers, Stephanie Fingerson, Rachel Cook, Karen Ballen, Alison Loren, Karilyn Larkin, Sally Arai, Muna Qayed, Sung Won Choi, Larisa Broglie, Bronwen E. Shaw, Steven Michael Devine, Antonio Martin Jimenez Jimenez
Institutions: City Of Hope National Medical Center, National Marrow Donor Program, Medical College of Wisconsin, Qatar University, Memorial Sloan Kettering Cancer Center, Wayne State University, The Barbara Ann Karmanos Cancer Institute, Moffitt Cancer Center, Dana-Farber Cancer Institute, Oregon Health & Science University, University of Virginia Health System, University of Virginia, University of Pennsylvania, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Stanford Health Care, Emory University, Children's Healthcare of Atlanta, University of Michigan, University of Miami
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1897780449, G4746067508, G5096073914, G5595967893, G6538849774, Cancer Center Support Grant, Cancer Center Support Grant, A Data Resource for Blood and Marrow Transplants and Adoptive Cellular Therapy Research, Blood and Marrow Transplant Clinical Trials Network DCC- The Medical College of Wisconsin, Inc., G911192202
OpenAlex ID: W4411330512