Impact of Race on Graft-Versus-Host Disease Rates after HLA-Matched Sibling Bone Marrow or Peripheral Blood Hematopoietic Cell Transplantation: Comparison of North American Caucasian Versus Japanese Populations

Background: The risk of acute graft-versus-host disease (aGVHD) after HLA-matched sibling bone marrow (BM) allogeneic hematopoietic cell transplantation (alloHCT) is lower in the Japanese than the Caucasians (Blood 2005, 105:1408). However, the impact of race on aGVHD might differ according to graft source (BM versus peripheral blood stem cell (PBSC)) in HLA-matched sibling alloHCT. To test this hypothesis, we analyzed data from the Center for International Blood and Marrow Transplant Research and the Japan Society for Hematopoietic Cell Transplantation.

Methods:  North American Caucasian and Japanese patients who received their first allogeneic BM or PBSC alloHCT from HLA-matched sibling for acute leukemia in complete remission or chronic leukemia in chronic or accelerated phase between 2000 and 2011 were eligible. Patients were 18 - 59 years old, received myeloablative conditioning regimen, and used cyclosporine or tacrolimus-based GVHD prophylaxis. Effect of race (Caucasian vs. Japanese), graft source (BM vs. PBSC), and their interaction on transplant outcomes was evaluated in the Cox proportional hazards model adjusting for other significant variables.

Results: Median ages of Caucasians and Japanese patients were 45 and 38 years, respectively. BM was used in 13% of the Caucasians, whereas it was used in 53% of the Japanese. Corresponding rates of tacrolimus-based GVHD prophylaxis were 68% and 7%. The cumulative incidence of grade 3-4 aGVHD at 100 days post BM alloHCT was 10 % and 6% in the Caucasians and Japanese, respectively, and that of grade 3-4 aGVHD post PBSC alloHCT was 14% and 10% in the Caucasians and Japanese, respectively (Figure 1). In multivariate analysis, the interaction term between race and graft source was not significant in any of the models, indicating that the impact of race on outcomes does not differ according to graft source. The risk of grade 3-4 aGVHD was significantly lower in Japanese compared to Caucasians (HR 0.74, 95% CI 0.57-0.96), which resulted in lower risk of non-relapse mortality (NRM) in Japanese compared to Caucasians patients (HR 0.69, 95% CI 0.54-0.89). The risk of relapse was also lower in Japanese compared to Caucasians patients (HR 0.75, 95% CI 0.63-0.89). Lower risk of NRM and relapse resulted in lower overall mortality rates in Japanese compared to Caucasians (HR 0.70, 95% CI 0.59-0.83). The risk of grade 3-4 aGVHD was significantly higher in PBSC compared to BM alloHCT recipients (HR 1.63, 95% CI 1.20-2.20), which resulted in higher NRM (HR 1.31, 95% CI 1.04-1.65) in PBSC compared to BM alloHCT recipients.

Conclusions: Irrespective of graft source, the risk of severe aGVHD was lower in Japanese patients, which resulted in the lower risk of NRM. The risk of severe aGVHD was higher in the PBSC alloHCT recipients, which resulted in the higher risk of NRM.

Figure 1 (A)        

Figure 1 (B)