Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis After Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation
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 ).
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (33)
Monzr M. Al Malki
1City of Hope, Duarte, United States
Stephanie Bo-Subait
2CIBMTR® (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, United States
Brent Logan
2CIBMTR/Medical College of Wisconsin, Milwaukee, United States
Janelle Olson
CIBMTR (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN
Jianqun Kou
2CIBMTR® (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, United States
Sarah Smith
Erin Leckrone
2CIBMTR® (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, United States
Juan Wu
Shanghai Public Health Clinical Center and Shanghai Institute of Infectious Diseases and Biosecurity, Fudan University
Heather E. Stefanski
Center for International Blood and Marrow Transplant Research, NMDP, Minneapolis, MN
Jeffery J. Auletta
CIBMTR (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN
Stephen R. Spellman
3Center for International Blood and Marrow Transplantation Research, National Marrow Donor Program, Minneapolis, MN
Craig Malmberg
2CIBMTR® (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, United States
Medhat Askar
2CIBMTR® (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, United States
Rachel Cusatis
1CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, United States
Brian C. Shaffer
1Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY
Dipenkumar Modi
8Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI
Farhad Khimani
H. Lee Moffitt Cancer Center, Tampa, Florida, United States
Mahasweta Gooptu
1Dana Farber Cancer Institute, Boston, United States
Mehdi Hamadani
12Blood and Marrow Transplant and Cellular Therapy Program, Medical College of Wisconsin, Milwaukee, WI
Abeer Madbouly
CIBMTR (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN
Martin Maiers
Stephanie Fingerson
CIBMTR (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN
Rachel Cook
1Oregon Health and Science University, Portland, United States
Karen Ballen
1University of Virginia Health System, Charlottesville, United States
Alison Loren
24University of Pennsylvania Medical Center, Philadelphia, United States
Karilyn Larkin
17Ohio State University Hospital, Columbus, United States
Sally Arai
Muna Qayed
Sung Won Choi
13Blood and Marrow Transplantation Program, University of Michigan, Ann Arbor, MI
Larisa Broglie
4CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, United States
Bronwen E. Shaw
CIBMTR (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI
Steven Michael Devine
CIBMTR (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN
Antonio Martin Jimenez Jimenez
Division of Transplantation and Cellular Therapy, University of Miami Miller School of Medicine, Miami, FL