Black Patients Have Greater Risk of Dying From GVHD Than White Patients

Black patients have a higher risk of nonrelapse mortality, mostly due to developing severe graft versus host disease (GVHD) following hematopoietic stem cell transplantation (HCT), according to a study published in Transplantation and Cellular Therapy.

While HCT, also known as bone marrow transplant, is increasingly used to treat and cure hematologic disorders, access to this treatment remains a concern for Black patients, who have lower rates of receiving HCT than White patients. During an HCT procedure, a patient is infused with healthy blood-forming stem cells. GVHD can develop after the transplant when the donated stem cells attack the patient’s own cells.

Black patients were more likely to develop severe graft versus host disease (GVHD) and have a higher risk of non-relapse mortality than White patients after hematopoietic stem cell transplantation.

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Development of acute GVHD after HCT has several well-known risk factors, such as cytomegalovirus infection and GVHD prophylaxis. However, there are also mixed results of research showing that people who are Black also are at risk for acute GVHD.

As access to HCT expands for racial minorities, “understanding the influence of race on HCT outcomes is of growing significance,” the authors noted. They conducted a retrospective analysis using data from the Mount Sinai Acute GVHD International Consortium to better understand differences in acute GVHD in Black and White patients, as well as what value GVHD biomarkers can play in identifying who might develop severe GVHD.

The study included data on 279 Black patients and 3,516 White patients who received HCT between 2014 and 2021. At baseline, there were several differences between the groups. For instance, the median age for Black patients was 28 years compared with 57 years for White patients. The researchers used propensity score matching to generate a matched cohort of 234 Black patients and 702 White patients who had similar baseline characteristics. In this new matched cohort, the median age was 29 years for Black patients and 31 years for White patients.

Black patients were more likely to undergo HCT for nonmalignant disorders (33% vs 19%) due to the high prevalence of sickle cell disease. In the United States, more than 90% of people with the disease are Black, with sickle cell disease occurring in 1 out of every 365 Black births.

For survivors, the median follow-up was 701 days for Black patients and 712 days in White patients.

Among the matched cohort with similar baselines, there were similarities in the first year:

• 34% of Black patients and 36% of White patients had GVHD in the first year requiring systemic therapy
• 29% of Black patients and 28% of White patients had maximum grades II-IV of acute GVHD
• 16% of Black patients and 19% of White patients had chronic GVHD

However, the cumulative incidence of maximum grades III-IV acute GVHD was significantly higher in Black patients (17%) compared with White patients (17%).

“The differences in GVHD severity at the time of GVHD onset were even more striking,” the authors wrote.

Due to more frequent lower gastrointestinal GVHD at symptom onset, Black patients were significantly more likely to need treatment for grade III-IV GVHD (39%) compared with White patients (21%).

Other similarities between the two groups were the median initiation day of systemic treatment (34 days for Black patients vs 37 days for White patients), the proportion receiving second-line treatment (27% vs 28%) and the proportion receiving ruxolitinib, the most frequently used second-line treatment (37% vs 32%).

Ultimately, Black patients had a significantly higher rate of nonrelapse mortality (18% vs 12%), which the authors wrote is consistent with more severe acute GVHD. For both Black and White patients, being older than 55 years of age, the stem cell source being cord blood, and a higher HCT-specific comorbidity index score were all associated with all risk factors for nonrelapse mortality.

The one-year overall survival was 6% lower among Black patients compared with White patients, and the cumulative incidence of nonrelapse mortality among patients receiving systemic treatment for acute GVHD was significantly higher for Black patients (26% vs 16%) within 12 months of treatment.

Initially the researchers thought the higher incidence of sickle cell disease among Black patients might account for the higher differences of acute severe GVHD and nonrelapse mortality, but the data didn’t support that.

Evaluating the serum biomarkers measured at the time of systemic treatment unveiled that all patients with AA1 GVHD had low nonrelapse mortality and as AA score increased the risk of non-relapse mortality for Black patients increased at a greater rate than the risk for White patients. For patients with AA3 GVHD the difference was large and statistically significant (71% vs 32%).

“The significantly worse outcomes for Black patients with AA3 GVHD compared with White patients partially explains the significantly worse NRM overall observed for Black patients," they determined.

The authors noted that the small number of Black patients included was one limitation of the study. In addition, patients who were also Hispanic were included in the Black cohort but not the White cohort.

“This study was not able to provide an explanation for differential risks by race, but the findings are perhaps not surprising given the observation of worse health outcomes for Black patients in other disease settings,” they concluded. “These findings, if confirmed in independent data sets, suggest that careful monitoring for GVHD is particularly important for Black patients.”