An Examination of Cytomegalovirus, Socioeconomic Status, Race, and Ethnicity on Outcomes after Haploidentical Hematopoietic Transplantation

Abstract

Previous analyses of the effects of race and socioeconomic status (SES) on outcomes after hematopoietic stem cell transplantation (HSCT) have suggested that minority populations and those in disadvantaged groups have inferior outcomes. However, the results of these studies have been inconsistent, potentially due to a multitude of factors, both medical and nonmedical, that have confounded results. In haploidentical (HI) HSCT, an expanding approach with the potential to enfranchise more minority patients, data on the effect of race and SES on outcomes are very limited. To identify and potentially correct factors that negatively impact outcomes after HI HSCT in disadvantaged groups at our institution, we performed a retrospective, multivariable analysis of the impact of race and SES as single and combined variables on HI HSCT outcomes of relapse, transplantation-related mortality, acute and chronic graft-versus-host disease (GVHD), and overall survival (OS). In addition to controlling for race and SES, all patients had HI donors and were treated with the same 2-step approach, with consistent T cell dosing and GVHD prophylaxis to further reduce the impact of confounders in this complex area. The study cohort of 239 patients was 71% Caucasian, 19.7% African American, 4.6% Hispanic, and 4.2% Asian. The majority of minority patients were in areas of higher deprivation (P = .001) and had the highest incidence of cytomegalovirus (CMV) seropositivity (P = .001) and the lowest likelihood of possessing a CMV immunodominant (IMD) allele (P = .001), which was previously associated with an OS benefit. Positive CMV serostatus was highly linked to post-transplantation CMV reactivation (P = .001) which was associated with higher relapse rates (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.06 to 2.30; P = .026), higher TRM (HR, 2.10; 95% CI, 1.09 to 4.05; P = .027), and lower OS (HR, 1.77; 95% CI, 1.18 to 2.65; P = .006). The lack of a CMV IMD allele largely replicated the results of CMV reactivation on HSCT results. Although race and SES did not directly correlate with either OS or relapse incidence, non-Caucasians in a more disadvantaged group had a higher incidence of chronic GVHD (HR, 2.55; 95% CI, 1.08 to 6.01; P = .033) compared with Caucasians and minorities in less disadvantaged groups. Regardless of SES, minorities had a lower incidence of acute GVHD than Caucasians in a more advantaged SES group (HR, 0.52; 95% CI, 0.30 to 0.90; P = .020). The primary finding of this study is that CMV reactivation was the major driver of mortality after HI HSCT. CMV reactivation may have be associated with poor HSCT outcomes in HI HSCT recipients in disadvantaged areas, most of whom were minorities. The data suggest that the prevention of post-transplantation CMV reactivation possibly could have a major impact on HI HSCT outcomes, especially in minority recipients. The finding of different GVHD manifestations between races are intriguing and merits further study.

Keywords: CMV; GVHD; Race; Socioeconomic status; allogeneic; haploidentical.