Racial Disparity in Outcomes after Myeloablative Conditioning for Hematological Malignancies in Patients Above the Age of 45 Years Undergoing Hematopoietic Stem Cell Transplantation
Authors: Mohapatra Satarupa , Abou Mourad Yasser , Cherniawsky Hannah , Chung Shanee , Forrest Donna L. , Kalia Gagan , Kuchenbauer Florian , Nantel Stephen H. , Narayanan Sujaatha , Nevill Thomas J. , Rodrigo Judith Anula , Roy Claudie , Sanford David , Song Kevin , Stubbins Ryan J , Toze Cynthia L. , White Jennifer , Lad Deepesh 
Published: December 2024

Introduction: The impact of race on outcomes of allogeneic hematopoietic cell transplants (HCT) has long been a field of research. The Center for International Blood and Marrow Transplant Research (CIBMTR) studies have shown worse survival for Blacks and Hispanics within the first year after HCT in the US (Morishima et al., 2022) but evened out for one-year survivors (Blue et al., 2023). We hypothesize that the outcomes of South Asians (age ≥ 45 years) receiving myeloablative conditioning in HCT for hematological malignancies are worse compared to other races and similar to that of Blacks (B). This is as per observations in South Asian regions where only reduced intensity conditioning is offered in this age group. British Columbia has a significant Asian population, with ~50% Whites (W), ~12% South Asians (SA) and 22% Other Asians (East Asians EA + South-East Asians SEA), which allows us to compare the HCT outcomes among these three racial groups.
Methods: This was a single-centre retrospective study conducted at the Leukemia/ BMT Program in BC. All patients (Age ≥ 45 years) undergoing myeloablative conditioning for hematological malignancies from January 2011 to December 2022 were included. The primary outcome was overall survival (OS). Secondary outcomes were non-relapse mortality (NRM), incidence of grade 2-4 acute graft versus host disease (GVHD), moderate-severe chronic GVHD and relapse incidence (RI). The survival analysis was done using Kaplan-Meier analysis and log-rank test. The GVHD, NRM and RI rates were calculated using the cumulative incidence of competing events and the Gray test. EZR was used for statistical analysis.
Results: Of the 487 patients, there were 28 (5.7%) South Asians (SA), 73 (15%) Other Asians (EA/SEA), and 382 (78%) Whites (W). Four Blacks (B) with similar outcomes as South Asians were grouped (SA/B) for outcome comparisons. There was a lower proportion of recipients ≥ 60 years of age in Asians than the Whites (SA/B 19% and EA/SEA 14%, W 34%, p=0.001). The proportion of donors ≥30 years of age was higher in the Asians compared to the Whites (SA/B 72%, EA/SEA 70%, and W 61%, p=0.02). The three groups were comparable regarding the recipient and donor sex, body mass index, and performance status. However, the proportion of SA/B with HCT-CI ≥ 5 was significantly higher (SA/B 34%, EA/SEA 15%, and W 7%, p=0.002). While the proportions with matched blood groups were similar, there were fewer CMV mismatches among the Asians (SA/B 25%, EA/SEA 26%, and W 43%, p=0.009). There was no difference in the conditioning type (total-body irradiation) and CD34 cell dose. However, a lower proportion of SA/B received ATG/PTCy as GVHD prophylaxis (SA/B 34%, EA/SEA 42%, and W 45%, p=0.0009).
The median OS was significantly shorter in SA/B (SA/B 13, EA/SEA 101 and W 64 months, p=0.02). The cumulative incidence of non-relapse mortality (NRM) was the highest in SA/B (SA/B 40%, EA/SEA 13.7% and W 16%, at two years, p=0.005). The cumulative incidence of acute and chronic graft versus host disease (GVHD) was not significantly different across the racial groups (p=0.6 and 0.7, respectively). The cumulative incidence of relapse was also not significantly different (p=0.6).
Discussion: Our study confirms that South Asians/Blacks ages ≥45 have worse survival after myeloablative conditioning. Supportive care is unable to overcome the differences in the outcomes. The high NRM is probably due to differences in comorbidities, frailty and pharmacogenetics and needs to be studied prospectively in multicentre studies.