Problems Associated with Community-Based Parenteral Anti-Infective Therapy with Intravenous Ganciclovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Abstract

Background: Our center utilized Cytomegalovirus (CMV) prophylaxis with intravenous ganciclovir (IV GCV) in allogeneic hematopoietic stem cell transplant (allo HSCT) recipients starting from engraftment to day +100. Most of this regimen was administered as communitybased parenteral anti-infective therapy (CoPAT). Surveillance CMV DNA detection by hybrid capture assay was done weekly through day +100 and at varying intervals thereafter. Methods: Retrospective review of the CoPAT database and electronic medical records to evaluate adherence to this protocol. Events were followed for 6 months from HSCT. Results: 66 patients underwent allo HSCT from 5/07 to 6/08. Demographics were similar in patients who received any prophylactic IV GCV (21 [32%]) and those who did not (45 [68%]. 36 patients did not receive CoPAT for appropriate reasons: CMV IgG donor negative & recipient negative (19), delayed engraftment (5), relapse of underlying disease (5), death within 100 days of HSCT (5), and refractory disease (2). Protocol deviation occurred in 23 patients (35%): IV GCV was not started due to physician or patient choice (5), was started appropriately, but stopped before D +100 due to physician or patient choice (4), was started for treatment of CMV viremia in a patient who should have been on prophylactic IV GCV before that point in time (8), and replacement of prophylactic IV GCV with oral valganciclovir (6). Other reasons for early discontinuation of prophylactic IV GCV before D +100 were leucopenia (6) and renal insufficiency (2). Median time from HSCT to starting CoPAT was 41 days. Median CoPAT duration was 45 days. Of the 30 appropriate candidates for prophylaxis, only 3 (10%) received the complete prophylaxis course from engraftment through day +100. In this nonrandomized study, the incidence of CMV viremia, peak viral load (VL) and graftversus-host disease (GVHD) were not significantly different between prophylaxed, partially prophylaxed, and unprophylaxed groups. Conclusion: In practice it proved to be difficult to administer and complete the IV GCV prophylaxis course. Reasons for this included delayed engraftment, relapsed or refractory underlying diseases, physician or patient individual choices, leucopenia, and renal insufficiency. This study illustrates the importance of assessing prophylaxis strategies in the context of actual clinical care. Valganciclovir; the L-valyl ester of GCV is 60% orally bioavailable; representing a more convenient and effective preventive alternative. Thus, in 1/09 we changed our CMV preventive strategy from universal prophylaxis to preemptive therapy with valganciclovir.