Background <p>Chronic hepatitis B virus (HBV) infection poses a significant challenge in immunocompromised populations, particularly among hematologic malignancy patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, data regarding the mechanisms underlying this alteration have only been partially reported. This study aimed to explore the kinetics of HBsAg and the potential for achieving functional cure (HBsAg loss) after allo-HSCT by analyzing longitudinal quantitative data from a complete cohort in patients with chronic HBV and hematologic malignancies.</p> Methods <p>A retrospective cohort study was conducted at the First Affiliated Hospital of Xi’an Jiaotong University from January 2013 to December 2023. Among the 622 consecutive allo-HSCT recipients, 15 patients with chronic HBV infection were included. Virological marker (HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc) and HBV DNA levels were monitored longitudinally before and after transplantation according to a standard protocol (baseline, weekly for the first month, monthly for 6 months, then every 3 months).The primary endpoint was HBsAg seroconversion, with exploratory outcome measures including HBV reactivation, cirrhosis decompensation, and mortality.</p> Results <p>Among the 15 patients, two (13.3%) achieved HBsAg seroconversion at 6 months and 12 months post transplantation. Both patients were HBeAg-negative, had undetectable HBV DNA before transplantation, and maintained HBsAg clearance during extended follow-up, with one patient discontinuing antiviral therapy. The remaining 13 patients (86.7%) remained HBsAg positive. Comparative analysis of the entire cohort’s longitudinal quantitative HBsAg data revealed distinct kinetic patterns between the two subgroups, providing preliminary insights into differential clearance trajectories. Non-liver-related causes mortality was observed, although four patients (26.7%) died from nonliver-related causes, primarily severe pneumonia or underlying hematologic disease. The mean follow-up duration was 165 weeks, with a median follow-up of 189 weeks for survivors.</p> Conclusion <p>This exploratory cohort study, utilizing complete longitudinal quantitative data, demonstrates that HBsAg clearance occurred in 2 of 15 patients post-HSCT and provides a comparative analysis of HBsAg kinetics between patients with and without clearance. These findings offer preliminary mechanistic clues and highlight the potential of allo-HSCT, alongside antiviral prophylaxis, as a safe context for exploring HBV functional cure in this high-risk population.</p> Clinical trial registration <p>Not applicable.</p>