Hepatitis B virus reactivation risk in haploidentical versus matched donor transplantation: Impact of universal prophylaxis

BACKGROUND: Hepatitis B virus reactivation is a serious complication of allogeneic hematopoietic cell transplantation, particularly in endemic regions. Patients with HBsAg-negative/anti-HBc-positive serology represent an intermediate-risk group due to occult hepatitis B virus infection. This study evaluated hepatitis B virus reactivation risk in haploidentical versus matched donor hematopoietic cell transplantation and assessed the effectiveness of Taiwan's universal prophylaxis policy. METHODS: A retrospective cohort study of 165 adult hematopoietic cell transplantation recipients with HBsAg-negative/anti-HBc-positive status was conducted at China Medical University Hospital, Taiwan from 2010-2025. The incidence of hepatitis B virus reactivation was compared between the pre-prophylaxis (2010-February 2021) and post-policy implementation (March 2021-2025) periods. Univariable associations, clinical outcomes, and temporal patterns were analyzed. RESULTS: Pre-prophylaxis, haploidentical recipients had higher reactivation rates (11.2%vs. 2.9%), but this did not reach statistical significance due to the small number of events (Odds ratio: 4.31; 95% CI: 0.67-37.55; p = 0.279). In the univariable analyses, hepatitis B virus reactivation was associated with chronic graft-versus-host disease (p = 0.001) and donor anti-HBs negativity (p = 0.001), with a median time to reactivation of 8.2 months. CONCLUSION: In this cohort, haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide was associated with a higher observed rate of hepatitis B virus reactivation than matched donor transplantation in HBsAg-negative/anti-HBc-positive recipients, although this difference was not statistically significant.