Exploring Outcomes By Ethnicity in Allogeneic Hematopoietic Cell Transplantation

Introduction In allogeneic hematopoietic stem cell transplantation (HCT) genetic and non-genetic factors are implicated in clinical outcomes 1,2,3. Studies have noted ethnic disparities in transplantation are affected by various factors like stem cell sources, conditioning therapies, and immunosuppressive regimens, resulting in discrepancies in mortality4. Specifically, there are observed inequities in mortality risk post HCT in the unrelated donor setting stratified by ethnicity {e.g., Asian (low risk), White (intermediate risk), and Black (high risk)}4. Outcomes have improved with the use of post-transplant cyclophosphamide (PTCY) for graft-versus-host-disease (GVHD) prophylaxis5 and the approval of Letermovir (LET) for cytomegalovirus (CMV) prevention in CMV seropositive patients6. Our study aimed to identify if disparities in outcomes are present by ethnicity as an avenue to identify future research targeting an equitable HCT experience. Patients and methods This retrospective study reviewed 709 consecutive patients who received HCT between January 2018 and April 2022 at the Princess Margaret Cancer Centre. The primary endpoint was Overall Survival (OS). Secondary endpoints included Cumulative Incidence of Relapse (CIR), Non-Relapse Mortality (NRM), Relapse Free Survival (RFS), and the composite endpoint GVHD-Free | Relapse Free Survival (GRFS). Results Stratified by self-described ethnicity, age, HCT-CI>/=3, and Human Leukocyte Antigen-Mismatched (HLA-MM) donor are statically significant variables. Black recipients were younger, had a higher incidence of HCT-CI>/= 3, and more often received HLA-MM. Figure 1. Ethnicity did not account for any statistically significant difference in 2-year outcomes: OS, RFS, NRM, CIR, or GRFS. Figure 2. CMV infection was highest in the East Asian patients (p<0.001). Figure 3. Multivariate analysis (MVA) revealed that Black patients had a hazard ratio (HR) of 2.4 (CI 1.3-4.6, p=0.006) for chronic GVHD (cGVHD). Epstein Barr Virus (EBV) infection inferred an HR of 1.5 times in the Black patients (CI 1.04-2.18, p=0.03). T cell depletion (TcD) increased the HR 3.14 for EBV infection (CI 1.39-7.09, p=0.0058) and HR 5.65 for CMV infection (CI 1.49-23, p=0.02) for all ethnic groups. In an MVA, Black ethnicity did not impact CMV reactivation, irrespective of donor type. Conclusions No significant difference in 2-year crucial transplant outcomes between ethnic groups was present. There was evidence of increased CMV reactivation in the East Asian patients, confirmed on MVA. Increased EBV reactivations and cGVHD were observed in Black patients and confirmed on MVA, without impact on GRFS. Stratifying by donor source, Black patients received more haploidentical donors; however, in MVA, no discernible effect on CMV reactivations was noted.