%0 Journal Article
%T Improving Safety of Preemptive Therapy with Oral Valganciclovir for Cytomegalovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation
%A Corinna Barkam
%A Haytham Kamal
%A Elke Dammann
%A Helmut Diedrich
%A Stefanie Buchholz
%A Matthias Eder
%A J邦rgen Krauter
%A Arnold Ganser
%A Michael Stadler
%J Bone Marrow Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/874601
%X Valganciclovir (VGC), an oral prodrug of ganciclovir (GCV), has been shown to clear cytomegalovirus (CMV) viremia in preemptive treatment of patients after allogeneic hematopoietic stem cell transplantation (alloHSCT), apparently without significant toxicity. Since VGC obviates hospitalization, it is increasingly being adopted, although not approved, in alloHSCT. When we retrospectively evaluated preemptive treatment with VGC versus GCV, foscarnet or cidofovir, in all 312 consecutive CMV viremias of 169 patients allotransplanted at our institution between 1996 and 2006, we found VGC more efficacious (79%) than non-VGC therapies (69%). The advantage of outpatient VGC, however, was outbalanced by more profound neutropenias (including two cases of agranulocytosis, one with graft loss) requiring subsequent prolonged rehospitalization. Thus, in a second, prospective cohort from 2007 to 2011 (all 202 consecutive CMV viremias of 118 yet older and sicker patients), we implemented twice weekly neutrophil monitoring during outpatient VGC treatment and avoided VGC maintenance therapy. While conserving efficacy (VGC 71%, non-VGC 72%), we could now demonstrate a reduced mean duration of hospitalization with VGC (9 days (0每66)) compared to non-VGC (25 days (0每115)), without any agranulocytosis episodes. We conclude that safe outpatient VGC therapy is possible in alloHSCT recipients, but requires frequent monitoring to prevent severe myelotoxicity. 1. Introduction Although mortality from cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (alloHSCT) has largely decreased with modern preemptive treatment, CMV viremias still contribute to significant morbidity and a considerable hospitalization burden for intravenous therapy with the standard first-line CMV drugs ganciclovir (GCV) and foscarnet (FCN). Valganciclovir (VGC), an orally available prodrug hydrolyzed to GCV, with a tenfold bioavailability compared to oral GCV [1], has been licensed for therapy of CMV retinitis in HIV disease and for CMV prophylaxis after solid organ transplantation, but not after alloHSCT, due to concern about its myelotoxicity, especially in long-term application. However, VGC has enjoyed widespread off-label use thanks to its outpatient applicability and its excellent bioavailability even in patients with impaired resorption due to intestinal graft-versus-host disease [2每4]. Several smaller trials and one large study found high efficacy (73%每100%) of VGC in the preemptive setting after alloHSCT ([5每14]; see Table 1), comparing favourably with standard
%U http://www.hindawi.com/journals/bmr/2012/874601/