Low-dose short-course intravenous ganciclovir as pre-emptive therapy for CMV viremia post allo-PBSC transplantation

Abstract

Summary:In contrast to allogeneic bone marrow transplantation (allo-BMT), there is a paucity of data on cytomegalovirus (CMV) infection and pre-emptive therapy (PT) strategies following allogeneic peripheral blood stem cell (allo-PBSC) transplantation. We report here on the patterns of CMV infection in a cohort of 225 patients following sibling donor allo-PBSC transplantation. In an attempt to reduce neutropenia, we used intravenous low-dose shortcourse (LDSC) ganciclovir (GCV) 5 mg/kg once daily for 21 days as preemptive therapy. A total of 165 recipientdonor pairs were CMV seropositive. An initial episode of viremia (detected by shell vial/tube culture) occurred in 75/165 (45%) at a median of day þ 35 (17-445) post allo-PBSC. In all, 58 patients received PT with LDSC GCV. Among 58, 55 (94%) completed the 21-day course of PT. A second episode of viremia occurred in 19/58 (33%) at day þ 80 (50-174) and a third episode in 5/58 (9%) at day þ 134 (103-218). Among patients receiving LDSC GCV, 5/58(9%) developed disease (four pneumonia, one colitis) at day þ 211 . No patient on LDSC GCV exhibited a decline in their ANC below 500/ll and none required growth factors. LDSC GCV is extremely well tolerated and cost-effective as PT for CMV viremia following allo-PBSC transplantation.

Once daily ganciclovir as initial pre-emptive therapy delayed until threshold CMV load ⩾10000 copies/ml: a safe and effective strategy for allogeneic stem cell transplant patients

“…15 The incidence of neutropenia was also low in the present cohort of patients as well. One patient required a treatment change to foscarnet and one patient required growth factor support secondary to declining ANC related to GCV.…”

“…15 In the current series, we delayed the initiation of ODG until a threshold CMV load of X10 000 copies/ml whole blood in 28 clinically stable patients. Ten of these patients (36%) required a dose increase to GCV 5 mg/kg twice daily for increasing viral loads.…”

“…We have previously shown GCV 5 mg/kg initiated once daily (ODG) to be a strategy for pre-emptive therapy that is effective and associated with minimal hematologic toxicity. 15 We now extend our pre-emptive therapy experience with ODG using a quantitative CMV PCR strategy to delay the initiation of ODG until a threshold CMV load of X10 000 copies/ml whole blood in clinically stable patients. Table 1.…”

Preemptive therapy with ganciclovir 5 mg/kg once daily for cytomegalovirus infection after unrelated cord blood transplantation

“…Favorable outcomes of preemptive therapy with GCV 5 mg/kg once daily for BMT and PBSCT recipients were previously reported. [5][6][7] In previous studies, dose-escalation of GCV or a change to foscarnet therapy was required in 32-39% patients when the initial response was not sufficient. Recurrence of CMV infection after the completion of initial preemptive therapy was observed in 33-43% patients.…”

“…4 In an attempt to reduce the incidence of GCV-related neutropenia, preemptive therapy with GCV 5 mg/kg once daily has previously been used as initial induction therapy for BMT and peripheral blood SCT (PBSCT) recipients. [5][6][7] The favorable outcomes suggested that this strategy could reduce the incidence of GCV-related neutropenia but retained the efficacy for preventing CMV disease in BMT and PBSCT recipients.…”