Allogeneic Hematopoietic Stem Cell Transplantation From HBsAg-Positive Donors Into HBsAg-Negative Recipients: A Safety and Practicable Regimen Under Active Prophylactic Anti-HBV Therapy

Transmission of hepatitis B virus (HBV) may occur (de novo HBV infection) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HBsAg-positive donors into HBsAg-negative recipients. Increased HBV associated complications will cause high morbidity and mortality post-transplantation in such patients. China is an endemic area for HBV infection. The exclusion of HBsAg positive donors will greatly limit the application of HSCT. There are few published data on allo-HSCT from HBsAg-positive donors when no other alternatives can be available. Recently great advances in anti-HBV therapy and prophylaxis have been achieved. The efficacy of allo-HSCT combined with anti-HBV prophylaxis in such patients remains unknown. In the current study, we performed a retrospective analysis of the virologic and clinical outcomes of allo-HSCT from HBsAg-positive donors into HBsAg-negative recipients under active prophylactic anti-HBV therapy. Methods From 2005 to 2010, a total of 10 HBsAg-negative recipients undergoing allo-HSCT from HBsAg-positive donors in our single center were included as an observation group. We performed a matched case-controlled analysis, in which each HBsAg-positive transplantation was paired with 3 control subjects selected from among all seronegative transplantation defining as a matched control group (30 patients). Patients were matched on age, underlying disease, disease stage, conditioning regimen and donor type. All the enrolled patients underwent HLA-matched related (20% each group) and HLA-mismatched related (haploidentical, 80% each group) transplantation. For haploidentical HSCT, conditioning regimen consisted of Ara-C, busulfan (Bu), cyclophosphamide (Cy), Me-CCNU and ATG. For HLA-matched related HSCT, the conditioning regimen consisted of Bu and Cy. GVHD prophylaxis consisted of cyclosporine A, mycophenolate mofetil and short-term methotrexate. Anti-HBV therapy consisted of lamivudine or entecavir for HBsAg positive donors. Marrow harvest and HSCT were performed until donor's serum HBV-DNA became undetectable. Hepatitis B immunoglobulin (HBIg) of 400 IU were administered to the recipients within 24 hours, 1 month and 2 months after stem cell infusion, respectively. HBsAb titers were detected once a month. If the titer was lower than 200IU/L, HBIg was injected rapidly. All the patients were followed-up weekly and HBV serology was detected once a month. Reults After transplantation, 1 and 0 patient developed HBV-related hepatitis in observation group and matched control group (P>0.05). The HBV-related hepatitis patient became positive for HBsAg 1 year post-transplantation with serum HBsAb loss. Interestingly, this patient became negative for HBsAg and positive for HBsAb after donor lymphocyte infusion due to the primary disease relapse. To date, none of the enrolled recipients in our study became positive for HBsAg. Veno-occlusive disease (VOD) is another kind of hepatic complication. One and 0 patient developed VOD in observation group and matched control group respectively (p>0.05). The presence of HBcAb in the absence of HBsAg in serum indicates past exposure to HBV. Despite the presumed resolution of the HBV infection in these patients, a minute amount of HBV DNA remains in the liver. So we analyzed HBcAb and HBsAb levels in the serum in both groups 1 year post-transplantation. Nine (90.0%) and 6 (20.0%) patients became positive for both HBcAb and HBsAb in observation group and matched control group respectively (p<0.01), suggesting possible occult HBV infection in recipients transplanted from HBsAg-positive donors. We also compared clinical outcomes between 2 groups. The incidence of aGVHD was 40.0% in obervation group and 30.0% in matched control group (p>0.05). The 1 year overall survival (OS) were 60.0% and 63.3% in observation group and matched control group respectively (p>0.05). The 1 year non-relapse mortality (NRM) were 10.0% and 13.3% in observation group and matched control group respectively (p>0.05). Conclusions Our data support that allo-HSCT from HBsAg-positive donors into HBsAg-negative recipients is a safety and practicable regimen under active prophylactic anti-HBV therapy, but these recipients are possibly complicated with occult HBV infection. A long-term prospective follow-up study on such patients is imperative currently.

No relevant conflicts of interest to declare.