Lamivudine therapy for a hepatitis B surface antigen (HBsAg)-positive leukemia patient receiving myeloablative chemotherapy and autologous stem cell transplantation

Abstract

Summary:Hepatitis B virus (HBV) can be a cause of fatal liver failure after chemotherapy for viral carrier patients and limits the indication of myeloablative therapy for them. We describe an HBsAg-positive leukemia patient who successfully underwent autologous PBSC transplant. After chemotherapeutic treatment his serum HBV DNA level rose in association with hepatitis. To prevent progression to fulminant hepatitis, we administered lamivudine, a viral reverse transcriptase inhibitor, during the transplantation procedure. The patient did not show any increase of HBV DNA or a worsening of his hepatitis. Thus, lamivudine may be a promising treatment for HBsAg-positive patients receiving myeloablative chemotherapy and autologous stem cell transplantation. Bone Marrow Transplantation (2000) 26, 1243-1245. Keywords: lamivudine; hepatitis type B; stem cell transplantation Reactivation of the hepatitis B virus (HBV) and subsequent fulminant hepatitis have been reported following myeloablative chemotherapy and stem cell transplantation for leukemia patients with HBV infection. 1 Interferon is effective in approximately 30% of such patients with chronic HBV infection. 2 However, adverse effects including fever, malaise, anorexia and depression are major concerns with interferon treatment. Lamivudine is a nucleoside analogue which specifically inhibits viral reverse transcriptase while suppressing HBV replication. 3 A trial of lamivudine for chronic HBV infection has demonstrated that it significantly reduces HBV DNA and alanine aminotransferase (ALT) levels. 4,5 In the present study, lamivudine was administered to an HBsAg-positive leukemia patient to prevent progression to fulminant hepatitis following autologous PBSC transplantation. Case reportA 33-year-old Japanese man was diagnosed with acute myelogenous leukemia (FAB classification, M2) and found to be an asymptomatic carrier of HBV. After achieving complete remission with induction chemotherapy, he received consolidation chemotherapy twice (Figure 1). 6 His clinical course was uneventful until following his second consolidation chemotherapy when HBV DNA and ALT levels increased to 3800 meq/ml (measured by branched DNA probe method 7 ) and 217 U/l, respectively. With bed rest only these levels decreased to normal by 3 months.Since his leukemic cells had poor prognostic karyotypes (trisomy 8 and 21), the patient decided to receive an autologous peripheral blood stem cell transplantation as further treatment. The pretransplant conditioning regimen consisted of busulfan, cytosine arabinoside and etoposide (BEA regimen). 6 Granulocyte colony-stimulating factor (G-CSF) was administered concurrently with the BEA regimen during conditioning. Lamivudine (Glaxo Wellcome Research and Development, Greenford, UK) 100 mg/day was administered orally starting on day −1. Peripheral blood stem cells (3.7 × 10 6 CD34 + cells/kg) which had been collected during recovery after consolidation chemotherapy were infused on day 0.Post transplantation, granulocytes exceeded 500 × 10 6 /l and...

Hepatitis reactivation and liver failure in haemopoietic stem cell transplants for hepatitis B virus (HBV)/hepatitis C virus (HCV) positive recipients: a retrospective study by the Italian group for blood and marrow transplantation

“…[15][16][17] In conclusion, this study defines the actual risk of severe liver disease after allogeneic and autologous HSCT in HBV-and HCV-infected patients and describes not only the severity but also the possible resolution of liver disease in these cases. Our results also indicate the need for further studies to identify the best approach for HBV-and HCVinfected patients who are in need of HSCT.…”

Successful allogeneic bone marrow transplantation from an HBV-positive donor into an HBV-positive recipient using lamivudine

“…10 Therefore, not prophylaxis but early initiation of this drug may be sufficient to inhibit HBV replication with careful monitoring of HBV-DNA levels. 11,12 Since mutation of HBV after administration of lamivudine has been reported, further studies to determine the optimal time of commencing the drug and the optimal duration of drug use is needed. 13 A prospective study on the effectiveness of lamivudine for BMT in HBV-positive patients and donors is warranted.…”

Prevention and treatment of viral infections in stem cell transplant recipients

“…In one study of eight HBV‐positive patients compared with 24 historical controls, famciclovir reduced the risk for post‐transplant hepatitis (Lau et al , 1998a). Another antiviral agent, lamivudine, with more potent anti‐HBV activity, has also been used in SCT patients to prevent reactivation (Picardi et al , 1998; Uchida et al , 2000; Endo et al , 2001). Additional studies are needed to assess the usefulness of these agents to prevent HBV‐associated complications in SCT recipients.…”