title: Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma.
abstract: Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. However, little is known about the risk of HBV reactivation after autologous hematopoietic stem cell transplantation (auto-HCT). We evaluated the incidence of HBV reactivation, liver toxicity, and survival in patients with multiple myeloma (MM) who received auto-HCT at our institution. We retrospectively identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (control subjects) who were matched for age, timing of auto-HCT from diagnosis, cytogenetics, disease status at transplant, induction therapy, and preparative regimen. All patients underwent auto-HCT between 1991 and 2013. Primary endpoints were HBV reactivation, defined as HBsAg positivity or ≥10-fold increase in HBV DNA, and hepatotoxicity, as defined in the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. In the resolved HBV infection group, 52 patients (49%) were HBsAb positive and 24 (22%) had detectable HBV DNA before auto-HCT. Only 1 patient with resolved HBV infection received pre-emptive antiviral therapy with lamivudine, whereas 4 patients received lamivudine (n = 3) or tenofovir (n = 1) at reactivation after auto-HCT for a median duration of 12 months. HBV reactivation occurred in 7 of 107 patients (6.5%) in the resolved HBV group. Median time to HBV reactivation from auto-HCT was 16 months. The cumulative incidence of grade 2 or greater hepatotoxicity was 30% in the resolved HBV infection group and 22% in the control group (hazard ratio, 1.3; 95% confidence interval, .7 to 2.3; P = .4). Nonrelapse mortality for the 2 groups was not statistically different at 2 years (P = .06), although it trended higher in the control group than in the resolved HBV infection group (8% versus 1%). The median progression-free survival (PFS) and overall survival (OS) durations in the resolved HBV infection and control groups were 21 versus 18 months (P = .5) and 53 versus 67 months (P = .2), respectively. Our data suggest that resolved HBV infection in patients undergoing auto-HCT for MM is associated with a low risk of HBV reactivation and hepatotoxicity; these complications were reversible and did not adversely affect the PFS or OS.
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Medicine, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas.
authors.forename: Ankur
authors.initials: A
authors.lastname: Varma
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Laura
authors.initials: L
authors.lastname: Biritxinaga
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Rima M
authors.initials: RM
authors.lastname: Saliba
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Stich
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Sarah Francesca
authors.initials: SF
authors.lastname: Jauch
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Aimaz
authors.initials: A
authors.lastname: Afrough
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Medhavi
authors.initials: M
authors.lastname: Honhar
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Uday R
authors.initials: UR
authors.lastname: Popat
authors.affiliation: Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Mehnaz A
authors.initials: MA
authors.lastname: Shafi
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Nina
authors.initials: N
authors.lastname: Shah
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Qaiser
authors.initials: Q
authors.lastname: Bashir
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Dinh
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address: mqazilba@mdanderson.org.
authors.forename: Muzaffar H
authors.initials: MH
authors.lastname: Qazilbash
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006510:Hepatitis B Antibodies / Q000097:blood*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy* / Q000821:virology; D012189:Retrospective Studies; D016019:Survival Analysis; D014182:Transplantation, Autologous / Q000009:adverse effects*; D014775:Virus Activation
chemical_list: D006510:Hepatitis B Antibodies
keywords: Multiple myeloma; Reactivation; Resolved HBV infection; Reverse seroconversion