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To the Editor:

We read with much interest the article by Lau and colleagues.1 They reported on the pre-emptive use of lamivudine in bone marrow transplant recipients to reduce the risk of hepatitis due to exacerbation of hepatitis B. In their study, only one of 20 HbsAg-positive patients had HBV-related hepatitis following transplantation. This patient received 100 mg of lamivudine daily at least 1 week before allogeneic hematopoietic cell transplantation, and this dosage was continued for 52 weeks after transplantation.

We recently encountered a 62-year-old Canadian woman of Filipino origin with acute myelogeneous leukemia who was in need of urgent life-saving bone marrow transplantation. The only possible match identified for donation was her brother, a 34-year-old man with known chronic hepatitis B infection: aspartate aminotransferase 28 U/L; alanine aminotransferase 56 U/L; bilirubin 10 μmol/L; albumin 41 g/L: INR 0.93; HbsAg positive, HbeAg positive; HBV DNA 4262 pg/mL (Digene Hybrid Capture System). His liver biopsy showed inflammation grade 1/4 and fibrosis stage 1/4.2

After the brother agreed to become a bone marrow donor, therapy with 300 mg of lamivudine daily was started to decrease his HBV viral load as rapidly as possible3 prior to bone marrow donation. Table 1 shows his serum HBV DNA levels sampled on a weekly basis while on lamivudine therapy until his bone marrow was harvested on week 6.

Table 1. 
 Week of Lamivudine Therapy
Baseline123456
HBV DNA (pg/ml)531941966201312Negative

To our surprise, the HBV DNA on the harvested tissue (peripheral blood stem cells) after 6 weeks of lamivudine therapy was 1330 pg/mL when it was negative in the serum. The recipient was HbsAg negative, HBcAb positive, and HbsAb positive prior to bone marrow transplant induction therapy, with no evidence of recurrent infection 6 months following the transplantation. She has received prophylaxis with lamivudine and hepatitis B–immune globulins. While still on lamivudine, the donor had a reappearance of HBV viremia 3 months after the donation. Lamivudine was then discontinued, followed by a return to baseline liver enzymes (alanine aminotransferase 54 U/L) and HBV DNA (HBV DNA 3828 pg/mL) levels.

HBV exacerbation is a serious cause of morbidity and mortality in patients receiving immunosuppression. We assumed that decreasing the viral load in the donor tissue would decrease the risk of transmitting the infection to the recipient. To our surprise, at a time when the donor had a very low serum HBV DNA level, the cells harvested from the bone marrow actually had a high viral load. We are unaware of any data regarding changes in viremia in this cellular compartment in patients receiving antiviral therapy. Although not tested, because of the short duration we doubt the high viral load detected in the harvested tissue was due to a lamivudine-resistant mutation. However, in retrospect one has to be concerned that the previous exposure to lamivudine offered to the donor may help the selection of drug-resistant mutations4 and lead to failure of future prophylaxis with lamivudine in the recipient.

Fourteen of the donors (group 1 and 2; see Table 1) in the study by Lau and colleagues were HbsAg-positive. We would be interested to know if the authors compared serum and bone marrow HBV DNA levels in some of their donors or if they have had a similar experience in treating a donor with lamivudine.

References

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M. Deschênes*, Pierre Laneuville†, * Division of Hepatology, Department of Medicine, McGill University Health Centre, Royal Victoria Hospital Site, 687 Pine Avenue, West, Montreal, Quebec, Canada, H4A 1A1, † Division of Hematology, Department of Medicine, McGill University Health Centre, Royal Victoria Hospital Site, 687 Pine Avenue, West, Montreal, Quebec, Canada, H4A 1A1.