Factors Associated with Acute and Chronic Graft-Versus-Host Disease after Matched Unrelated Donor Hematopoietic Cell Transplantation Using Posttransplant Cyclophosphamide-Based GvHD Prophylaxis

Background: Graft-versus-host disease (GVHD) is a challenging complication following allogeneic hematopoietic cell transplantation (HCT), significantly impacting patients' quality of life and contributing to high morbidity and mortality. This study aimed to investigate the factors associated with the development of grade II-IV acute GVHD (aGVHD) and chronic GVHD (cGVHD) in patients undergoing matched unrelated donor (MUD) HCT with posttransplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis.

Methods: In this multicenter retrospective study, we included recipients of MUD HCT with PT-Cy-based GVHD prophylaxis from 2013 to 2018, identified from the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry dataset (P5646, Ramathan et al). Univariate Cox regression analyses were performed to identify predictors of GVHD. Multivariate Cox regression was performed to assess independent predictors of GVHD. Hazard ratios (HR) with 95% CI were calculated. SPSS version 28 was used for data analysis, and p<0.05 was considered statistically significant.

Results: We included 206 MUD HCT recipients receiving PT-Cy-based GVHD prophylaxis. The median age was 62.5 (48.9-67.3) years, and 121 (58.7%) were male. Hematologic diagnoses were acute myeloid leukemia (AML) in 107 (51.9%) patients, acute lymphocytic leukemia (ALL) in 25 (12.1%) patients, and myelodysplastic syndrome (MDS) in 74 (36%) patients. The Karnofsky performance status (KPS) was 80% in 16% (n=33), 80-89% in 25.2% (n=52), and 90% or higher in 57.3% (n=118) of patients. The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) was 0 in 15.5% (n=32), 1-2 in 28.6% (n=59), 3-4 in 39.9% (n=82), and five or higher in 16.5% (n=34) of patients. Myeloablative conditioning was used in 54.4% (n=112) of patients. Bone marrow (BM) graft was used in 32.5% (n=67) of patients and 67.5% (n=139) received a peripheral blood stem cell (PBSC) graft. Grade II-IV aGVHD was noted in 41.3% (n=85) of patients, while 34.5% (n=71) of patients developed cGVHD. Univariate regression analyses were performed for age, gender, ethnicity/race, KPS, HCT-CI, conditioning intensity, graft type, donor-recipient sex match, donor-recipient CMV match, body mass index, and hematologic diagnoses (AML, ALL, MDS). The only predictor of grade II-IV aGVHD was age (HR 0.986, 95% CI 0.972-0.999, p=0.042), while male gender (0.548, 95% CI 0.343-0.874, p=0.012) and donor-recipient sex mismatch (HR 2.172, 95% CI 1.360-3.468, p=0.001) predicted a higher risk of cGVHD. In the adjusted multivariate model, independent predictors of cGVHD included donor-recipient sex mismatch, KPS <90% (HR 2.968, 95% CI 1.479-5.955, p=0.002), and HCT-CI >0 (HR 3.024, 95% CI 1.219-7.5, P=0.017).

Conclusion: In matched unrelated donor HCT recipients with posttransplant cyclophosphamide (PT-Cy)-based GVHD prophylaxis, donor-recipient sex mismatch, lower Karnofsky Performance Status, and higher comorbidity index predicts the risk of chronic GVHD. Conditioning intensity, graft type, and other factors do not appear to influence the risk of GVHD.