Few data are available to date on the dose of oral valganciclovir as cytomegalovirus (CMV) preemptive therapy in stem cell transplantation patients. This study aimed to evaluate the efficacy and safety of low-dose valganciclovir (900 mg/day) as preemptive treatment in allotransplanted recipients. Valganciclovir was used in 34 patients who underwent allogeneic stem cell transplantation for hematological malignancies at the dose of 900 mg oral administration/day (12 patients, group 1) or 1,800 mg oral administration/day (22 patients, group 2). Thirty-two out of 34 patients (94%) obtained negativization of polymerase chain reaction for CMV at a median of 12.5 days from the beginning of valganciclovir administration (10/12 patients of group 1, 22/22 patients of group 2). We conclude that oral administration of valganciclovir can induce clearance of CMV viral load in about 2 weeks; moreover, lower-dose oral valganciclovir (900 mg/day) has a comparable efficacy to the proposed standard dose (1,800 mg/day).

Keywords:
Cytomegalovirus infection, Stem cell transplantation, Valganciclovir
1.
Paya C, Humar A, Dominguez E, Washburn K, Blumberg E, Alexander B, Freeman R, Heaton N, Pescovitz MD; Valganciclovir Solid Organ Transplant Study Group: Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant 2004;4:611–620.
2.
Singh N, Wannstedt C, Keyes L, Gayowski T, Wagener MM, Cacciarelli TV: Efficacy of valganciclovir administered as preemptive therapy for cytomegalovirus disease in liver transplant recipients: impact on viral load and late-onset cytomegalovirus disease. Transplantation 2005;79:85–90.
3.
Segarra-Newnham M, Salazar MI: Valganciclovir: a new oral alternative for cytomegalovirus retinitis in human immunodeficiency virus-seropositive individuals. Pharmacotherapy 2002;2:1124–1128.
4.
Martin DF, Sierra-Madero J, Walmsley S, Wolitz RA, Macey K, Georgiou P, Robinson CA, Stempien MJ; Valganciclovir Study Group: A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med 2002;346:1119–1126.
5.
Devyatko E, Zuckermann A, Ruzicka M, Bohdjalian A, Wieselthaler G, Rödler S, Wolner E, Grimm M: Pre-emptive treatment with oral valganciclovir in management of CMV infection after cardiac transplantation. J Heart Lung Transplant 2004;23:1277–1282.
6.
Cvetković RS, Wellington K: Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients. Drugs 2005;65:859–878.
7.
Einsele H, Reusser P, Bornhäuser M, Kalhs P, Ehninger G, Hebart H, Chalandon Y, Kröger N, Hertenstein B, Rohde F: Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation. Blood 2006;107:3002–3008.
8.
van der Heiden PL, Kalpoe JS, Barge RM, Willemze R, Kroes AC, Schippers EF: Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients. Bone Marrow Transplant 2006;37:693–698.
9.
Ayala E, Greene J, Sandin R, Perkins J, Field T, Tate C, Fields KK, Goldstein S: Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2006;37:851–856.
10.
Meijer E, Boland GJ, Verdonck LF: Prevention of cytomegalovirus disease in recipients of allogeneic stem cell transplants. Clin Microbiol Rev 2003;16:647–657.
11.
Candoni A, Simeone E, Tiribelli M, Pipan C, Fanin R: What is the optimal dosage of valganciclovir as preemptive therapy for CMV infection in allogeneic hematopoietic SCT? Bone Marrow Transplant 2008;42:207–208.
12.
Ljungman P, Reusser P, de la Camara R, Einsele H, Engelhard D, Ribaud P, Ward K; European Group for Blood and Marrow Transplantation: Management of CMV infections: recommendations from the infectious diseases working party of the EBMT. Bone Marrow Transplant 2004;33:1075–1081.
13.
Junghanss C, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG, Chauncey T, McSweeney PA, Little MT, Corey L, Storb R: Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study. Blood 2002;99:1978–1985.
14.
Hambach L, Stadler M, Dammann E, Ganser A, Hertenstein B: Increased risk of complicated CMV infection with the use of mycophenolate mofetil in allogeneic stem cell transplantation. Bone Marrow Transplant 2002;29:903–906.
15.
Jiwa NM, Van Gemert GW, Raap AK, Van de Rijke FM, Mulder A, Lens PF, Salimans MM, Zwaan FE, Van Dorp W, Van der Ploeg M: Rapid detection of human cytomegalovirus DNA in peripheral blood leukocytes of viremic transplant recipients by the polymerase chain reaction. Transplantation 1989;8:72–76.
16.
Bai X, Hosler G, Rogers BB, Dawson DB, Scheuermann RH: Quantitative polymerase chain reaction for human herpesvirus diagnosis and measurement of Epstein-Barr virus burden in posttransplant lymphoproliferative disorder. Clin Chem 1997;43:1843–1849.
17.
Laurenti L, Piccioni P, Cattani P, Cingolani A, Efremov D, Chiusolo P, Tarnani M, Fadda G, Sica S, Leone G: Cytomegalovirus reactivation during alemtuzumab therapy for chronic lymphocytic leukemia: incidence and treatment with oral ganciclovir. Haematologica 2004;89:1248–1252.
18.
Winston DJ, Baden LR, Gabriel DA, Emmanouilides C, Shaw LM, Lange WR, Ratanatharathorn V: Pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir in allogeneic stem cell transplant patients with graft-versus-host disease of the gastrointestinal tract. Biol Blood Marrow Transplant 2006;12:635–640.
19.
Keven K, Basu A, Tan HP, Thai N, Khan A, Marcos A, Starzl TE, Shapiro R: Cytomegalovirus prophylaxis using oral ganciclovir or valganciclovir in kidney and pancreas-kidney transplantation under antibody preconditioning. Transplant Proc 2004;36:3107–3112.
20.
Gabardi S, Magee CC, Baroletti SA, Powelson JA, Cina JL, Chandraker AK: Efficacy and safety of low-dose valganciclovir for prevention of cytomegalovirus disease in renal transplant recipients: a single-center, retrospective analysis. Pharmacotherapy 2004;24:1323–1330.
© 2010 S. Karger AG, Basel
2010
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