Correlation Between Body Mass Index and Leucopenia After Administration of Valganciclovir for Cytomegalovirus Infection in Chinese Cardiac Recipients

Abstract

ytomegalovirus (CMV) infection is an importantcomplication after solid organ transplantation. It is believed that more than 50% of transplant recipients are affected by this troublesome complication, which causes graft failure and mortality if the infection is not treated promptly. 1 The risk factors include CMV-seronegative recipients who receive organs from CMV-seropositive donors or CMV-seropositive recipients who received anti-Tcell antibodies, such as anti-thymocyte globulin or muromonab-CD3 (Orthoclone OKT3), for induction of immunosuppression. [2][3][4] Preemptive treatment of CMV infection is a crucial strategy in transplant recipients. Valganciclovir (VGC) has shown its superiority over the intravenous and oral form, ganciclovir, by its convenience, better bioavailability and potency. 5 It is also an effective prophylaxis for CMV infection in high-risk transplant recipients, 6 and for treatment of CMV retinitis in patients with acquired immunodeficiency syndrome. 7 Several clinical studies have reported that VGC therapy can cause varying degrees of leucopenia, which may counteract the benefits of the therapy. However, the risk factors associated with VGC-induced leucopenia in patients undergoing solid organ transplantation are still not well understood, especially in Oriental recipients. We analyzed the clinical data from before and after VGC therapy in cardiac transplant recipients to clarify the incidence of unexpected leucopenia and the risk factors. Methods PatientsAn institutional review board-approved retrospective chart was conducted from September 2005 to August 2006 and 61 cardiac recipients whose quantitative real-time CMV-polymerase chain reaction (PCR) showed positive results during their monthly check-ups were enrolled. VGC was then prescribed for 3 months at a dosage according to their renal function; 32 developed severe leucopenia after VGC treatment. Leucopenia is defined here as a decrease in the white blood cell (WBC) count greater than 50% of the pre-VGC WBC count or WBC count <3,000 cells/mm 3 . The 61 study subjects were categorized into a leucopenia or non-leucopenia group for further analysis. VGC UsageThe VGC dosage was correlated to the estimated creatinine clearance (900 mg/day if Ccr ≥60 ml/min; 450 mg/day if 60 ml/min >Ccr ≥40 ml/min; 450 mg every other day if 40 ml/min >Ccr ≥25 ml/min; 450 mg twice per week if 25 ml/min >Ccr ≥10 ml/min). We discontinued or reduced the VGC dosage as soon as severe leucopenia developed. Monthly Check-upsThe monthly check-ups for all the cardiac tranplant recipients included complete blood counts, lymphocyte subpopulation, quantitative real-time CMV-PCR, tacrolimus or cyclosporine level, and biochemistry panels. EndomyoCirc J 2007; 71: 968 -972 (Received October 18, 2006; revised manuscript received February 15, 2007; accepted March 5, 2007

Leukopenia in Kidney Transplant Patients With the Association of Valganciclovir and Mycophenolate Mofetil

“…12,13 It is noteworthy that higher incidences of leukopenia and/or neutropenia have been found in studies involving a small number of patients, probably causing some bias. 12,13 In contrast to our study, Rerolle et al 12 observed severe infectious complications associated with neutropenia. The difference from our patients may result from the intensive monitoring, and prompt use of G-CSF.…”

“…To our knowledge, there is only one study that looked at risk factors associated with VGC-induced leukopenia. 13 Chen et al 13 demonstrated that VGC toxicity was related to low body mass index, suggesting that dose should be adjusted to body weight, as racial or genetic factors may be important.…”

Mycotic Aneurism in Renal Transplantation Associated to Persistent Leucopenia. Case Report and Review of the Literature

“…When the renal function is decreased, the half-life of the drug can increase up to 13 times. It has not been reported to MMF itself cause bone marrow toxicity with such severity; however, in cases of aplastic anemia induced by valganciclovir (confirmed by biopsy) it has been observed increase in serum free fraction of MMF, which could explain the synergistic effect for the development of leucopenia [5,6].…”

“…In a prospective analysis by Brum, et al searching for risk factors for the development of leucopenia, they found that the use of valganciclovir and MMF, the origin of the graft (higher risk in deceased donor) and the start of the prophylaxis in the first post transplant day were the most related factors [6,7]. The main side effect of valganciclovir is leucopenia, which occurs in 10-55% and atinine 1.0 mg/dl).…”

Mycophenolate mofetil-induced agranulocytosis in a renal transplant recipient

“…Transplant recipients are known to develop neutropenia frequently, especially in the early posttransplant period, with incidence reported at 4.9% and 37.5% in two studies [4,5]. Although the etiology of neutropenia is often multifactorial (viral or other systemic infection, malignancy including posttransplant lymphoproliferative disorders, etc.…”