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Failure of long-term lamivudine prophylaxis in patients with resolved hepatitis B infection undergoing chemotherapy and allogenic hematopoietic stem cell transplantation for hematological malignancies: two case reports

Hepatitis B virus (HBV) reactivation is a well known complication in patients with resolved HBV infection, i.e., HBsAg negative, hepatitis B core antibody (anti-HBc) positive ± antibodies against HBsAg (anti-HBs), undergoing chemotherapy (CT) and/or allogenic hematopoietic stem cell transplantation (HSCT) for onco-hematological diseases. In these patients, this risk can be prevented by either “pre-emptive anti-HBV therapy”, based on the monitoring of HBV DNA and/or HBsAg, followed by rescue therapy with anti-HBV regimens, or by “anti-HBV prophylaxis” based on the administration of nucleos(t)ides analogs (NUCs) during immunosuppression and for a consolidation time after the end of immunosuppressive drugs. As per standard procedure in our centre, all patients with hematological malignancies and a resolved HBV infection receive lamivudine (LMV) prophylaxis at the time of CT or HSCT to be maintained for at least 18 months after the discontinuation of immunosuppressive drugs. Herein, we describe two patients with resolved HBV infection who, following allogenic HSCT and repeated cycles of CT for hematological malignancies, developed HBsAg seroreversion due to the late emergence of LMVresistance (R) during long-term LMV prophylaxis. Case A. A 56-year-old Italian male was diagnosed with micromolecular IgG kappa multiple myeloma (MM) on June 2008. Since the virological profile was consistent with a resolved HBV infection with positive anti-HBe and anti-HBs (240 IU/L) and undetectable serum HBV DNA (<12 IU/mL), LMV prophylaxis was started concomitantly with CT initiation. Between January 2009 and December 2010, several cycles of CT were administered (Table 1 and Figure 1). In December 2010, a matched unrelated donor (MUD) HSCT was carried out (donor HBV profile: HBsAg negative, anti-HBs 715 IU/L, antiHBc negative) and cysclosporin (CSA) as a prophylaxis and treatment of graft versus host disease (GvHD) was started to be progressively reduced and withdrawn in May 2012. However, in April 2012, MM relapsed requiring further cycles of CT without, nevertheless, achieving complete disease remission. In November 2015, the patient was enrolled in a phase I/II trial based on the coadminstration of carfilzomib+pomalidomide+dexamethasone. Between 2008 and November 2015, the patient remained persistently negative for HBsAg, HBeAg