Prophylactic therapy with oral low-dose valgancyclovir in cytomegalovirus-positive allogeneic stem cell transplant recipients

Pretransplant cytomegalovirus (CMV) seropositivity in allogeneic stem cell transplant (HSCT) recipients is associated with the highest risk of CMV reactivation. The efficacy and safety of low dose oral valgancyclovir (VGCV) as CMV reactivation prophylaxis was retrospectively evaluated in 32 cytomegalovirus-seropositive HSCT recipients (30 HLAmatched related and 2 unrelated HSCT) with a median age of 40 years (range 18-59). Primary diseases were acute myeloid leukemia (19), acute lymphoblastic leukemia (4), non Hodgkin’s lymphoma (3), multiple myeloma (3) and myelodysplastic syndrome (3). Fifteen received a myeloablative conditioning regimen, while 17 patients received a reducedintensity conditioning regimen. Twenty-one patients received graft-versus- host disease (GVHD) prophylaxis with cyclosporine-A (CsA) and methotrexate (MTX), and the others CsA with MTX and anti-thymocyte globulin. Graft source was mainly mobilized peripheral blood stem cells (80%). Seventeen HSCT recipients were transplanted in first complete remission (CR), the remaining in second CR (6) or with advanced disease (7). The median follow-up post-HSCT was 30±12 months. CMV infection was monitored weekly using polymerase chain reaction (PCR). VGCV was administered orally at dose of 450 mg daily for six months. Six patients (18%) developed asymptomatic early and late positive CMV-PCR on average 56 days after HSCT successfully treated with VGCV at 1800 mg/day, except one who developed fatal gastrointestinal CMV disease. At the time of CMV reactivation, four patients had been affected by grade II-IV acute GVHD and two by an extensive chronic GVHD. None of the patients required discontinuation of the oral VGCV secondary to specific gastrointestinal intolerance. Hematologic toxicity, such as mild anemia, neutropenia and thrombocytopenia was documented in seven cases (22%), but did not required drug discontinuation. The rate of non CMV-related infections was 25% and was similar in both groups with and without CMV reactivation. At the end of the follow-up, 18 of 32 patients were alive with a median follow up of 31 months (range 2-56). Relapsed-related mortality was 20%, transplant- related mortality was 9% and did not differ between group with and without CMV reactivation. Our data suggest that low dose VGCV is safe and effective as CMV reactivation prophylaxis in allogeneic CMVseropositive HSCT recipients. These results require further validation in prospective randomized studies.