Discussion
Older studies, well summarized by Majhail et al indicate racial disparities associated with access to HCT as well as outcomes after HCT (11). Analyses of data from 1988-2002 including hospital discharge data, CIBMTR, SEER and US Census bureau data indicated that when compared to W, adult B patients were less likely to receive HCT for hematologic malignancies. (12,13) However, these differences in access to HCT were not present in younger patients. (12,14) All patients in our study received HCT and thus had access to this tertiary center, high-cost care. We did not have data that would allow evaluation of access to transplant by race. Indirect evidence, such as racial distribution of our patients (75% W, 18% B and 3% Asians), which correlated well with overall Florida population (2018 US Census Bureau estimates) comprising 75% W (53% Non-Hispanic White), 16% B and 2.8 % Asians, and time from diagnosis to transplant, which was actually 3 months shorter in B than W children, suggests that access to transplant was not an issue.
However, B and W HCT recipients do not have the same access to HLA-matched donors. Increased diversity in HLA haplotypes among B populations, and underrepresentation of minorities in national bone marrow registries contribute to difficulty in finding fully matched unrelated donors for B patients and other minority HCT-recipients. (4,15) Only 16 B children (29%) in our study received a fully HLA-matched HCT during this 10-year period.
The largest study describing the effects of race and socioeconomic status on outcomes of unrelated donor HCT (1995-2004), which included ~1600 children <20 years, did not differentiate outcomes based on age. (7) When adult and pediatric populations were analyzed together, Baker et al showed that African-Americans but not Asian or Hispanic HCT recipients of unrelated donor transplants had significantly worse overall survival than W. African-Americans as well as Hispanics had higher treatment-related mortality than W. Also, patients with median income in the lowest quartile across racial groups, had worse OS and higher risk of treatment related mortality (7). Our study indicated that the majority of B patients (71%) and 53% of W patients received an HLA-mismatched/alternative donor HCT. This is similar to Baker’s study where 78% of B and 54% W received an HCT from a MMUD (7). Despite a larger proportion of HLA-mismatched transplants among B children in our study, overall survival and other outcomes were not different between W and B HCT recipients. In addition, unlike W, who had a significantly lower survival after HLA-mismatched HCT, which is well described in the literature, B HCT recipients had identical outcomes after HLA-matched and HLA-mismatched transplants. Only 16 B patients received a fully-HLA matched transplant over a 10 year period and survival rates in this group were likely skewed due to low patient numbers. Although more B than W patients received HLA-mismatched HCT, they were more likely to receive MMRD, than MMUD BM or PB. Black children receiving MMRD/haploidentical transplant had a 2-year survival rate of 70%,that did not subsequently decline. Although we do not have details of GVHD prophylaxis for patients receiving alternative donor transplants, all 5 FPBCC centers utilize post-transplant cyclophosphamide (PTCy), while only one center has the access to in vitro T-cell depletion. Recent reports indicate improved outcomes of recipients of haplo-identical HCT using PTCY for GVHD prophylaxis. (16) Similar to our findings, a recent randomized study indicated improved overall survival in haploidentical HCT recipients with PTCY comparing with recipients of MMUCB transplant. (17) Although deaths due to relapse and treatment-related causes were not different between W and B HCT-recipients, we noticed an unacceptably high rate of death (22-25%) due to treatment-related causes. Lowering those rates for all children will be one of the FPBCC priorities.
Despite limitations of our study including relatively small number of patient, lack of data on socio-economic status, ethnic origin, and lack of detailed data on GVHD prophylaxis, this is the largest contemporary pediatric study examining outcomes by race in children with HM undergoing HCT. Overall, our results are encouraging as they show that lack of HLA-matched donors did not translate into adverse HCT outcomes for B children.