Management of allogeneic bone marrow transplant recipients at risk for cytomegalovirus disease using a surveillance bronchoscopy and prolonged pre-emptive ganciclovir therapy

Background: Patients undergoing allogeneic bone marrow transplant (BMT) are considered to be at increased risk of cytomegalovirus (CMV) disease if the y and/or their donor are CMV seropositive pre-transplant. Although several pre-emptive strategies have been shown to be effective in preventing early CMV disease, the ability of pre-emptive strategies using prolonged ganciclo vir therapy to reduce the incidence of late-onset CMV infection, disease an d mortality has not been fully evaluated. Objective: To assess the efficacy of 18 weeks of pre-emptive ganciclovir th erapy in preventing late-onset (> 100 days post-transplant) CMV disease whe n administered to asymptomatic BMT patients found to have CMV in bronchoalv eolar lavage (BAL) fluid obtained during a surveillance bronchoscopy approx imately 35 days post-transplant. To determine whether or not survival of BM T recipients iS influenced by pre-transplant donor and recipient CMV serost atus in the context of this pre-emptive ganciclovir strategy. Study Design: Consecutive patients undergoing allogeneic BMT were assessed for their risk of developing CMV disease based on their pre-transplant CMV serostatus and that of their donor. Patients who were CMV seropositive and/ or received marrow from a CMV seropositive donor underwent a surveillance b ronchoscopy and BAL approximately 35 days post-transplant. Patients with po sitive BAL fluid for CMV received pre-emptive ganciclovir therapy for 18 we eks at decreasing dose levels. Patients considered to be at low risk for th e development of CMV disease (donor and recipient CMV seronegative) were fo llowed without intervention. Results: Of 98 consecutive patients, 55 were considered to be at risk for C MV disease and underwent a surveillance bronchoscopy. Sixteen (29%) patient s had a positive BAL fluid for CMV and were started on pre-emptive ganciclo vir therapy. Two patients progressed and died with CMV-related pneumonia. O ne additional patient developed CMV-related enteritis on day 42 post-transp lant and recovered with continuing ganciclovir treatment. Of the 39 patient s with a negative BAL fluid for CMV, one developed a fatal CMV pneumonia 15 0 days post-transplant and two additional patients developed gastrointestin al CMV disease 28 and 57 days post-BMT, respectively. None of the patients in the low risk group developed CMV disease. Conclusions: The strategy utilizing a surveillance bronchoscopy for CMV and initiating prolonged (18 weeks) pre-emptive ganciclovir therapy for patien ts with a positive BAL fluid for CMV resulted in a low incidence of CMV-rel ated post-transplant complications. After a minimum follow-up of 16 months, late CMV reactivations (occurring > 100 days post-transplant) were not obs erved in the group of individuals pre-emptively treated with ganciclovir. T his observation suggests that prolonged therapy with a reduced dose of ganc iclovir may be important in the prevention of CMV reactivation. The CMV ser ostatus of donors and recipients prior to BMT did not correlate with surviv al. (C) 1999 Elsevier Science B.V. All rights reserved.