Donor Type Does Not Impact Late Graft Failure Following Reduced Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Based Graft-Versus-Host Disease Prophylaxis

Cindy Lynn Hickey; Mei-Jie Zhang; Mariam Allbee-Johnson; Rizwan Romee; Navneet S Majhail; Monzr M Al Malki; Joseph H Antin; Cara L Benjamin; Christopher Bredeson; Saurabh Chhabra; Michael R Grunwald; Yoshihiro Inamoto; Christopher G Kanakry; Filippo Milano; Robert J Soiffer; Scott R Solomon; Stephen R Spellman; Claudio G Brunstein; Corey Cutler

doi:10.1016/j.jtct.2024.12.021

Donor Type Does Not Impact Late Graft Failure Following Reduced Intensity Allogeneic Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide Based Graft-Versus-Host Disease Prophylaxis

Transplant Cell Ther. 2025 Jan 2:S2666-6367(24)00840-6. doi: 10.1016/j.jtct.2024.12.021. Online ahead of print.

Authors

Cindy Lynn Hickey¹, Mei-Jie Zhang², Mariam Allbee-Johnson³, Rizwan Romee⁴, Navneet S Majhail⁵, Monzr M Al Malki⁶, Joseph H Antin⁴, Cara L Benjamin⁷, Christopher Bredeson⁸, Saurabh Chhabra⁹, Michael R Grunwald¹⁰, Yoshihiro Inamoto¹¹, Christopher G Kanakry¹², Filippo Milano¹³, Robert J Soiffer¹⁴, Scott R Solomon¹⁵, Stephen R Spellman¹⁶, Claudio G Brunstein¹⁷, Corey Cutler¹⁸

Affiliations

¹ Memorial University of Newfoundland, Division of Hematology, Newfoundland, Canada.
² Division of Biostatistics, Data Science Institute, Medical College of Wisconsin, Milwaukee, WI; CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI.
³ CIBMTR® (Center for International Blood and Marrow Transplant Research), Medical College of Wisconsin, Milwaukee, WI.
⁴ Dana-Farber Cancer Institute, Division of Transplantation and Cellular Therapy, Boston, MA.
⁵ Sarah Cannon Transplant and Cellular Therapy Network, Nashville, TN.
⁶ City of Hope, Department of Hematology and Hematopoietic Cell Transplantation, Duarte, CA.
⁷ University of Miami Miller School of Medicine, Department of Medicine, Miami, FL.
⁸ Ottawa Hospital TCT Programme and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
⁹ Division of Hematology/Oncology, Department of Medicine, Mayo Clinic Arizona, Phoenix, AZ.
¹⁰ Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC.
¹¹ Department of BMT & Cellular Therapy, Fujita Health University School of Medicine, Toyoake, Japan.
¹² Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
¹³ Fred Hutchinson Cancer Center, Translational Science and Therapeutics Division, Seattle, WA.
¹⁴ Dana Farber Institute, Division of Hematologic Malignancies, Boston, MA.
¹⁵ Blood and Marrow Transplant Program, Northside Hospital Cancer Institute, Atlanta, GA.
¹⁶ CIBMTR® (Center for International Blood and Marrow Transplant Research), NMDP, Minneapolis, MN.
¹⁷ Cleveland Clinic, Taussig Cancer Institute, Department of Hematology and Oncology, Cleveland, OH.
¹⁸ Dana-Farber Cancer Institute, Division of Transplantation and Cellular Therapy, Boston, MA. Electronic address: corey_cutler@dfci.harvard.edu.

PMID: 39755256
DOI: 10.1016/j.jtct.2024.12.021

Abstract

Background: Post-transplant cyclophosphamide (PTCy) is a commonly used graft-vs-host disease (GVHD) prophylaxis, particularly in the setting of haploidentical (haplo) hematopoietic cell transplantation (HCT). The rate of graft failure has been reported to be as high as 12-20% in haplo-HCT recipients using PTCy. The objective of this study was to determine if donor type influenced the risk of late graft failure following RIC HCT using PTCy-based GVHD prophylaxis.

Study design: A retrospective cohort analysis using the CIBMTR research database among adult patients who underwent first reduced intensity conditioning (RIC) haplo or 8/8 MUD HCT between 2011 and 2018 for AML, ALL or MDS with PTCy GVHD prophylaxis. The primary outcome was incidence of late graft failure, defined as secondary graft loss in the absence of relapse, or poor graft function requiring a cellular therapy intervention.

Results: A total of 1336 patients met the eligibility criteria (1151 haplo, 185 MUD). Patients in the MUD group were older (65 vs 61), less ethnically diverse (95% vs 72% Caucasian), received fewer bone marrow grafts (45% vs 16%), and had younger donors (median age 28 vs 37 years old). Conditioning regimens were predominately fludarabine, cyclophosphamide and total body irradiation (87% haplo and 38% MUD). At 2 years, the adjusted probabilities of late graft failure for the haplo group was 6.5% ((95% confidence interval (CI) 5.2-8.0)) vs 5.9% (95% CI 2.7-10.9) for the MUD group (p=0.79). Multivariate analysis for risk factors associated with late graft failure found associations with a diagnosis of MDS (HR 1.98; 95% CI 1.22-3.20; p=0.005), and earlier year of HCT (2015-2018 vs. 2011-2014; HR 0.39; 95% CI 0.24-0.64; p=0.0002). A post-hoc sensitivity analysis was performed to evaluate the effect of donor age and use of PBSC grafts. Graft failure did not differ between haplo and MUD HCT (HR 1.19; p=0.67) when adjusted for donor age nor when restricted to PBSC grafts only (HR 0.85; p=0.70).

Conclusion: In this registry-based analysis of patients undergoing RIC HCT for AML, ALL or MDS using GVHD prophylaxis with PTCy, there was no significant difference in late graft failure rates between haplo and MUD donors. Overall rates of late graft failure were high.

Keywords: Graft Rejection; graft failure; post-transplant cyclophosphamide.