Correlates of Graft Versus Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

Background: Graft versus host disease (GVHD) remains one of the most common and therapeutically challenging post-transplant complications contributing to reduced quality of life and high morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HCT). Several studies have reported the factors affecting the development of GVHD. We aimed to investigate the factors associated with acute GVHD (aGVHD) and chronic GVHD (cGVHD) following allo-HCT.

Methods: For this retrospective study, we included all patients undergoing matched unrelated donor (MUD) and haploidentical (haplo) allo-SCT at the University of Kanas Medical Center from August 2016 to July 2021. Descriptive statistics were used for baseline characteristics. Univariate analyses were performed for all variables, continuous and categorical. Logistic regression was performed for aGVHD and cGVHD. Odds ratios (0R) with 95% CI were calculated. SPSS version 28 and R version 4.16 were used for data analysis. Statistical significance was considered at p<0.05.

Results: The study included 452 allo-HCT recipients, with a median age of 57 (18-77) years, and 61% (277) were male. Hematologic diagnoses included myeloid (n=322, 71%), lymphoid (n=101, 22%), and others (n=29, 7%). Karnofsky's performance status (KPS) was 60-80% in 67% (n=304) of patients and 90% or higher in 33% (n=148) of patients. The donor type was MUD in 61 % (n=276) and haplo in 39% (n=176). Myeloablative and reduced-intensity conditioning were performed in 169 (37%) and 283 (63%) recipients. The graft source was bone marrow (BM) in 224 (49.6%) and 228 (50.4%) had peripheral blood stem cell (PBSC) grafts. GVHD prophylaxis included tacrolimus/methotrexate (Tac/MTX, n=241, 53%) and post-transplant cyclophosphamide-based (PT-Cy, n=211, 47%). Most of the MUD HCT recipients (n=241, 81%) received Tac/MTX and all haplo HCT recipients received PT-Cy for GVHD prophylaxis. Fifty-one percent (n=230) developed grade II-IV aGVHD and 10% (n=45) developed grade III-IV aGVHD at day 100 post-transplant. One-year cGVHD was noted in 63% (n=287) of the patients and 37% (n=168) of the patients had extensive cGVHD. In the MUD HCT cohort, 51% developed grade II-IV aGVHD compared to 50% for the haplo HCT cohort (p=0.773), and 45% of the MUD HCT group developed one-year cGVHD compared to 35% of the haplo HCT group (p=0.04). In the univariate analysis, the only predictor of grade II-IV cGVHD included gender (male vs female, HR 0.59, 95% CI 0.40-0.87, p=0.007) while predictors of cGVHD included KPS (60-80% vs ≥90%: HR 0.64, 95% CI 0.43-0.96, p=0.029), graft type (BM vs PBSC: HR 0.67, 95% CI 0.47-0.99, p=0.049), and donor type (MUD vs haplo: HR 1.52, 95% CI 1.03-2.25, p=0.035). In the multivariate model, independent predictors of cGVHD included KPS (60-80% vs ≥90%: HR 0.62, 95% CI 0.41-0.92, p=0.018), graft type (BM vs PBSC: HR 0.58, 95% CI 0.39-0.86, p=0.008), and donor type (MUD vs haplo: HR 1.77, 95% CI 1.18-2.67, p=0.006). History of grade II-IV acute GVHD significantly predicted the risk of chronic GVHD (OR 1.66, 95% CI 1.14-2.43, p=0.008).

Conclusion: In this single-center study, female recipients had a higher risk of acute GVHD while peripheral blood stem cell graft, matched unrelated donors (probably because of use of Tac/MTX prophylaxis as compared to PT-Cy in haploidentical donors), higher Karnofsky performance status, and a history of acute GVHD significantly predicted a higher risk of chronic GVHD.

McGuirk:Envision: Consultancy; NEKTAR therapeutics: Consultancy; CRISPR therapeutics: Consultancy; Caribou bio: Consultancy; Sana technologies: Consultancy; Allo Vir: Consultancy; BMS: Consultancy; Kite: Consultancy; Autolus: Consultancy; Novartis: Consultancy; Legend biotech: Consultancy. Mushtaq:Iovance Biotherapeutics: Research Funding.