Impact of Hepatitis B Core Antibody (HBcAb) Seropositivity on the Outcome of High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Background: Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg)-negative. We evaluated the incidence of hepatitis B reactivation and liver toxicity in patients with multiple myeloma (MM) who received high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (auto-HCT) at our institution.

Methods: We identified 108 patients with resolved hepatitis B infection (HB infection= HBcAb positive, HBsAg negative) and 138 patients with normal HB serology (control) who were matched for age, time of auto-HCT, disease status and preparative regimen. Both groups received HDC + auto-HCT between 1989 and 2012. Primary endpoints were: 1) HB viral reactivation: HBsAg positivity or 10-fold increase in HB viral DNA; 2) hepatotoxicity, as defined in NCI CTCv3.0.

Results: There were no significant differences in immunoglobulin subtype, bone marrow plasmacytosis, serum beta-2 microglobulin, albumin, creatinine or lactic dehydrogenase (LDH) between the HB infection or the control group. Approximately 70% in each group received melphalan alone as preparative regimen. In the HB infection group, 52 patients (48%) were HBsAb-positive, and 23 (21%) had detectable HB viral DNA prior to auto-HCT. Serum HB viral DNA level was <100 IU/m in 22 patients, and <300 IU/ml in 1 patient. HB e antigen (HBeAg) was non-reactive in all 4 patients evaluated prior to auto-HCT. Only 1 patient with HB infection received pre-emptive antiviral therapy with Lamivudine, while 4 patients received Lamivudine (3) or Tenofovir (1) at reactivation for a median duration of 1 year. HB viral reactivation was seen in 6 of 108 (5.6%) in the HB infection group vs. 0 of 138 in the control group (p=0.006). There was a >10-fold increase in HB viral DNA in 5 of 6 patients with HB viral reactivation, and in 2 of 5 HBeAg also became reactive. Median time to HB reactivation from auto-HCT was 2.6 years. NCI CTCv3.0 grade 1, 2, 3 or 4 increase in alanine transferase, aspartate transferase, total bilirubin or alkaline phosphatase was seen in 6, 1, 2 and 3 patients, respectively in the HB infection group (9.3%) vs. 1, 2, 0 and 1 (2.9%) patients in the control group (p= 0.049). Only one patient (0.9%) in the HB infection group vs. 6 (4.3%) in control group died of non-relapse causes within 1-year of auto-HCT (p=0.13).With a median follow up of 30 and 28 months in HB infection vs. control groups, the median PFS was 21.4 and 18.7 months, respectively (p=0.66). Median OS in HB infection and control groups was 57.0 vs. 65.2 months, respectively (p=0.93).

Conclusion: Resolved HB infection is associated with a significant risk of HB viral reactivation and hepatotoxicity in patients undergoing auto-HCT for MM. These complications were reversible and were not associated with an increase in TRM, PFS or OS.