Risk Factors of Changes in Hepatitis B Antibody Status after Allogeneic Hematopoietic Stem Cell Transplantation in Chinese Children with Thalassemia Major
Authors: Feng Xiaoqin , Long Lina , Li Chunfu 
Published: October 2019

Abstract
Objective: This retrospective study evaluated the risk factors involved in the changes in HBsAb status in patients with thalassemia major at a single center in China.
Methods: A total of 104 children who underwent allo-HSCT, using NF-08-TM transplant protocol in our center, between January 2010 and June 2012 were recruited.Hepatitis B markers, including HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were examined by TRFIA (time-resolved fluoroimmunoassay) or ELISA (Enzyme-Linked Immunosorbent Assay) for recipients before and after allo-HSCT (at least up to 6 months) and for donors prior to transplantation. HBsAg positive recipients and donors received lamivudine antiviral therapy before allo-HSCT and the treatment was continued in recipients up to 6 months post transplantation.
The demographic and clinical characteristics of the patients and their donors were summarized by descriptive statistics. For identification of risk factors that influenced the post-transplant anti-HBs loss and HBV reactivation, both univariate and multivariate logistic regression was used, and odds ratio (OR) and 95% confidence interval (CI) were determined for the covariates that were shown to be statistically significant. All tests were 2-sided, with the type I error rate fixed at 0.05. Statistical analyses were performed using IBM SPSS 20 (SPSS Statistics V20, IBM Corporation, Somers, New York).
Results: Of the 104 patients, 2（1.9%） recipients were positive for HBsAg and 102（98.1%） recipients were negative for HBsAg. Of the 102 patients negative for HBsAg before transplantation, the proportion of positive anti-HBs was 69.6% (71 of 102 patients). Of the 104 donors, 99 (95.2%)were negative for HBsAg and 5 (4.8%)were positive for HBsAg. Of the 99 donors negative for HBsAg before transplantation, 72 donors (72.7%) had anti-HBs. After transplantation, of the 69 patients, 27 (39.1%) patients lost their HBV immunity in a median follow-up period of 30 months (range: 21–45); the remaining 42 (60.9 %) patients maintained the immunity against HBV after a median follow-up period of 28.5 months (range: 19–46). 33 patients were anti-HBs negative before the allo-HSCT. The 33 patients included 11 patients with donors who had no anti-HBs and 22 patients with donors who had anti-HBs. After the allo-HSCT, 15 of the 33 patients were found to have newly gained HBV immunity, as represented by the presence of anti-HBs. While 14 of them who developed adoptive immunity had immunized donors (63.6%; 14 out of 22), 1 of them (9.1%; 1 out of 11) with a non-immunized donor (donors without anti-HBs) also had developed HBV immunity.
Multivariate logistic regression analysis of 104 patients who underwent allo-HSCT revealed that, patients with pre-HSCT titer of HBsAb < 257.47mIU/mL (adjusted odds ratio, 10.5, 95% CI, 2.1–53.3) and HBsAb-immunized donors (51.3, 2.8–938.6) were significant risk factors for post allo-HSCT HBV loss and acquisition, respectively. In addition, the post-transplant HBV reactivation rate was 11.1%.
Conclusions: Current results indicate that pre-transplant HBsAb titer is a key determinant in the loss of HBV immunity after allo-HSCT and HBsAb negative patients with immunized donors are more likely to gain HBV immunity after allo-HSCT than those with non-immunized donors. Further, preemptive antiviral treatment with lamivudine significantly reduces HBV reactivation. This is the first study to have indicated the significant predictors of changes in HBsAg status in children with thalassemia major.

Disclosures
No relevant conflicts of interest to declare.