Allogeneic marrow transplantation in patients positive for hepatitis B surface antigen

Abstract Twenty patients who were positive for hepatitis B surface antigen (HBsAg) underwent allogeneic marrow transplant for malignancy or other underlying hematologic disease between 1975 and 1986. After transplant, one patient had serologic evidence of hepatitis B virus (HBV) reactivation whereas three patients had evidence of an immune response to HBV. Among four patients with serologic follow-up of 1 year or more, three remained positive for HBsAg and one became HBsAg negative. Six patients (30%) developed clinical evidence of venocclusive disease and seven patients (35%) developed acute graft-versus-host disease involving the liver, but the incidence of these complications was similar to that expected among patients who are not carriers of HBsAg. Three patients died with hepatorenal failure, but all three had venocclusive disease and the contribution of HBV infection to liver failure was unclear. Available liver specimens obtained at autopsy (six patients) or biopsy (two patients) all showed either HBsAg (one specimen) or hepatitis B core antigen (four specimens) or both (three specimens) by immunoperoxidase staining. Although HBV reactivation leading to hepatic failure has been reported among allogeneic marrow transplant recipients as well as other immunocompromised patients, we did not observe an increase in the incidence of severe liver disease after transplant among these 20 patients positive for HBsAg at the time of transplant, and do not consider positivity for HBsAg to be a contraindication to allogeneic marrow transplantation.

Download Full-text

Allogeneic marrow transplantation in patients positive for hepatitis B surface antigen

Blood ◽

10.1182/blood.v77.1.195.bloodjournal771195 ◽

1991 ◽

Vol 77 (1) ◽

pp. 195-200 ◽

Cited By ~ 1

Author(s):

EC Reed ◽

D Myerson ◽

L Corey ◽

JD Meyers

Keyword(s):

Hepatitis B ◽

Surface Antigen ◽

Marrow Transplantation ◽

Hepatitis B Surface Antigen ◽

Marrow Transplant ◽

Core Antigen ◽

Immunoperoxidase Staining ◽

Hbv Reactivation ◽

Allogeneic Marrow Transplantation ◽

Allogeneic Marrow

Twenty patients who were positive for hepatitis B surface antigen (HBsAg) underwent allogeneic marrow transplant for malignancy or other underlying hematologic disease between 1975 and 1986. After transplant, one patient had serologic evidence of hepatitis B virus (HBV) reactivation whereas three patients had evidence of an immune response to HBV. Among four patients with serologic follow-up of 1 year or more, three remained positive for HBsAg and one became HBsAg negative. Six patients (30%) developed clinical evidence of venocclusive disease and seven patients (35%) developed acute graft-versus-host disease involving the liver, but the incidence of these complications was similar to that expected among patients who are not carriers of HBsAg. Three patients died with hepatorenal failure, but all three had venocclusive disease and the contribution of HBV infection to liver failure was unclear. Available liver specimens obtained at autopsy (six patients) or biopsy (two patients) all showed either HBsAg (one specimen) or hepatitis B core antigen (four specimens) or both (three specimens) by immunoperoxidase staining. Although HBV reactivation leading to hepatic failure has been reported among allogeneic marrow transplant recipients as well as other immunocompromised patients, we did not observe an increase in the incidence of severe liver disease after transplant among these 20 patients positive for HBsAg at the time of transplant, and do not consider positivity for HBsAg to be a contraindication to allogeneic marrow transplantation.

Download Full-text

Hepatitis B Virus Reactivation in Lymphoma Patients With Prior Resolved Hepatitis B Undergoing Anticancer Therapy With or Without Rituximab

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.0182 ◽

2009 ◽

Vol 27 (4) ◽

pp. 605-611 ◽

Cited By ~ 436

Author(s):

Winnie Yeo ◽

Tung C. Chan ◽

Nancy W.Y. Leung ◽

Wai Y. Lam ◽

Frankie K.F. Mo ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

B Cell Lymphoma ◽

Anticancer Therapy ◽

Hbv Dna ◽

Core Antigen ◽

Hbv Reactivation ◽

B Virus

Purpose Reactivation of hepatitis B virus (HBV) infection is a well-recognized complication in cancer patients with chronic HBV (hepatitis B surface antigen [HBsAg] positive) undergoing cytotoxic chemotherapy. In patients who have resolved HBV (HBsAg negative and antibody to hepatitis B core antigen [anti-HBc] ± antibody to hepatitis B surface antigen [anti-HBs] positive), such incidence has been much less common until recent use of rituximab. In this study on HBsAg-negative/anti-HBc–positive lymphoma patients, the objectives were to determine the HBV reactivation rate in patients treated with rituximab-containing chemotherapy and to compare it with the rate in patients treated without rituximab. Patients and Methods Between January 2003 and December 2006, all patients diagnosed with CD20+ diffuse large B-cell lymphoma (DLBCL) had HBsAg determined before anticancer therapy. They were treated with either cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) alone or rituximab plus CHOP (R-CHOP). HBsAg-negative patients had anti-HBc determined; serum was stored for anti-HBs and HBV DNA. All patients were observed for HBV reactivation, which was defined as detectable HBV DNA with ALT elevation during and for 6 months after anticancer therapy. Results Among 104 CD20+ DLBCL patients, 80 were HBsAg negative. Of the latter, 46 patients (44.2%) were HBsAg negative/anti-HBc positive; 25 of these patients were treated with CHOP, and none had HBV reactivation. In contrast, among the 21 patients treated with R-CHOP, five developed HBV reactivation, including one patient who died of hepatic failure (P = .0148). Exploratory analysis identified male sex, absence of anti-HBs, and use of rituximab to be predictive of HBV reactivation. Conclusion Among HBsAg-negative/anti-HBc–positive DLBCL patients treated with R-CHOP, 25% developed HBV reactivation. Close monitoring until at least 6 months after anticancer therapy is required, with an alternative approach of prophylactic antiviral therapy to prevent this potentially fatal condition.

Download Full-text

Hepatitis B Virus Reactivation by Immunosuppressive Therapy in Patients with Autoimmune Diseases: Risk Analysis in Hepatitis B Surface Antigen-negative Cases

The Journal of Rheumatology ◽

10.3899/jrheum.110289 ◽

2011 ◽

Vol 38 (10) ◽

pp. 2209-2214 ◽

Cited By ~ 32

Author(s):

MASARU KATO ◽

TATSUYA ATSUMI ◽

TAKASHI KURITA ◽

TOSHIO ODANI ◽

YUICHIRO FUJIEDA ◽

...

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Autoimmune Diseases ◽

Immunosuppressive Therapy ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Hbv Dna ◽

Core Antigen ◽

Hbv Reactivation ◽

B Virus

Objective.To evaluate the risk of reactivation of resolved hepatitis B virus (HBV) by immunosuppressive therapy in patients with autoimmune diseases.Methods.Thirty-five patients with autoimmune diseases were included in our study; all were hepatitis B surface antigen (HBsAg)-negative and antibody against hepatitis B core antigen-positive. They were followed for 8–124 weeks and clinical outcomes were analyzed, including serum levels of HBV-DNA and aminotransferase every 4 weeks during their immunosuppressive therapy for underlying autoimmune diseases. If HBV-DNA was detected during the immunosuppressive therapy, HBsAg, antibody against HBsAg (anti-HBs), hepatitis B e antigen (HBeAg), and antibody against HBeAg were also monitored every 4 weeks.Results.HBV-DNA was detected in 6 out of 35 patients. Anti-HBs titer was significantly lower in the patients in whom HBV-DNA was detected compared with the others at baseline: 2.83 (range 0.24–168.50) mIU/ml vs 99.94 (range 0.00–5342.98) mIU/ml, respectively (p = 0.036). Outcomes of the 6 patients with HBV reactivation were as follows: HBV-DNA turned negative in 2 patients without nucleic acid analog (NAA) and 1 with NAA; 2 died due to bacterial sepsis; and 1 died due to autoimmune hemolytic anemia. Significant elevation of aminotransferase was found in only 1 patient, but HBsAg converted to positive in 2 patients and HBeAg converted to positive in 1 patient.Conclusion.Reactivation of resolved HBV can occur during standard immunosuppressive therapy for autoimmune diseases. The low titer of baseline anti-HBs may carry its risk.

Download Full-text

Cytomegalovirus antigen detection in peripheral blood leukocytes after allogeneic marrow transplantation

Blood ◽

10.1182/blood.v80.5.1358.1358 ◽

1992 ◽

Vol 80 (5) ◽

pp. 1358-1364 ◽

Cited By ~ 162

Author(s):

M Boeckh ◽

RA Bowden ◽

JM Goodrich ◽

M Pettinger ◽

JD Meyers

Keyword(s):

Marrow Transplantation ◽

Gastrointestinal Disease ◽

Marrow Transplant ◽

Cmv Infection ◽

Culture Methods ◽

Blood Leukocytes ◽

Shell Vial ◽

Allogeneic Marrow Transplantation ◽

Peripheral Leukocytes ◽

Allogeneic Marrow

Abstract Detection of cytomegalovirus (CMV) antigenemia was compared with shell vial centrifugation cultures for rapid detection of CMV infection. In a prospective study, 59 CMV seropositive patients were monitored weekly during the first 100 days after allogeneic marrow transplantation for virus excretion from urine, throat, and blood and for antigenemia by direct staining of peripheral leukocytes using an antibody pool directed against pp 65. Antigenemia was present in 21 of 22 patients with culture-proven CMV infection and in 3 of 37 without culture-proven CMV infection (sensitivity 95%, specificity 91%). The median time of onset of antigenemia and shell vial cultures was day 47 and 55 after transplant, respectively (P = .0006). Among patients who developed CMV disease without preceding cultures, antigenemia was detected in all patients with CMV pneumonia (N = 6) and in two of three patients with gastrointestinal disease by a median of 10 and 7 days, respectively, before the onset of disease (P = .0002). Levels of antigenemia were significantly higher in patients with disease or viremia than in patients with excretion from urine or throat (P less than .05). Whether the antigenemia assay is more sensitive than rapid culture methods to focus antiviral prophylaxis in marrow transplant patients must be determined in controlled studies.

Download Full-text

Comparison of Three Third-Generation Tests for Hepatitis B Surface Antigen with the Radioimmunoassay Test for Antibody to Core Antigen

Military Medicine ◽

10.1093/milmed/148.5.406 ◽

1983 ◽

Vol 148 (5) ◽

pp. 406-409

Author(s):

Joel Alcoff ◽

William Kellogg ◽

Burton Leeb

Keyword(s):

Hepatitis B ◽

Surface Antigen ◽

Hepatitis B Surface Antigen ◽

Core Antigen ◽

Third Generation

Download Full-text

Hepatitis B reactivation in a hepatitis B surface antigen-negative patient after allogeneic bone marrow transplant: successful treatment with lamivudine and seroconversion

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2009.01.007 ◽

2009 ◽

Vol 64 (1) ◽

pp. 80-82 ◽

Cited By ~ 2

Author(s):

Rosa Pérez-Grande ◽

Nieves Gutiérrez-Zufiaurre ◽

Santiago Muñoz-Criado ◽

Ana M. Blázquez de Castro ◽

Lourdes Vázquez López ◽

...

Keyword(s):

Bone Marrow ◽

Hepatitis B ◽

Bone Marrow Transplant ◽

Surface Antigen ◽

Successful Treatment ◽

Hepatitis B Surface Antigen ◽

Marrow Transplant ◽

Allogeneic Bone ◽

Negative Patient ◽

Allogeneic Bone Marrow Transplant

Download Full-text

Low Risk of Hepatitis B Virus Reactivation in HBsAg-negative/Anti-HBc–positive Carriers Receiving Rituximab for Rheumatoid Arthritis: A Retrospective Multicenter Italian Study

The Journal of Rheumatology ◽

10.3899/jrheum.151105 ◽

2016 ◽

Vol 43 (5) ◽

pp. 869-874 ◽

Cited By ~ 27

Author(s):

Valentina Varisco ◽

Mauro Viganò ◽

Alberto Batticciotto ◽

Pietro Lampertico ◽

Antonio Marchesoni ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Hepatitis B Virus ◽

Hepatitis B ◽

Hepatitis B Surface Antigen ◽

Hbv Dna ◽

Hbv Infection ◽

Core Antigen ◽

Hbv Reactivation ◽

Serum Hbsag ◽

B Virus

Objective.Patients with resolved hepatitis B virus (HBV) infection, i.e., hepatitis B surface antigen (HBsAg)-negative/antihepatitis B core antigen (anti-HBc)-positive, undergoing rituximab (RTX)-based chemotherapy for hematological malignancies without anti-HBV prophylaxis are at risk of HBV reactivation, but the risk in such patients receiving RTX for rheumatological disorders is not clear. We evaluated this risk in HBsAg-negative/anti-HBc–positive patients with rheumatoid arthritis (RA) undergoing RTX without prophylaxis.Methods.Thirty-three HBsAg-negative/anti-HBc–positive outpatients with RA with undetectable HBV DNA by sensitive PCR assay [73% women, median age 60 years, 85% with HBsAg antibodies (anti-HBs), 37% with antihepatitis B envelope antigen] received a median of 3 cycles of RTX (range 1–8) over 34 months (range 0–80) combined with disease-modifying antirheumatic drugs (DMARD) without prophylaxis. All underwent clinical and laboratory monitoring during and after RTX administration, including serum HBsAg and HBV DNA measurements every 6 months or whenever clinically indicated.Results.None of the patients seroreverted to HBsAg during RTX treatment, but 6/28 (21%) showed a > 50% decrease in protective anti-HBs levels, including 2 who became anti-HBs–negative. One patient (3%) who became HBV DNA-positive (44 IU/ml) after 6 months of RTX treatment was effectively rescued with lamivudine before any hepatitis flare occurred. Among the 14 patients monitored for 18 months (range 0–70) after RTX discontinuation, no HBV reactivation was observed.Conclusion.The administration of RTX + DMARD in patients with RA with resolved HBV infection leads to a negligible risk of HBV reactivation, thus suggesting that serum HBsAg and/or HBV DNA monitoring but not universal anti-HBV prophylaxis is justified.

Download Full-text