Effect of blood cyclosporine concentration on the outcome of hematopoietic stem cell transplantation from an HLA-matched sibling donor

Abstract

We retrospectively evaluated the effect of the blood cyclosporine (CsA) concentration on the outcome of allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor in 171 patients who received a continuous infusion of CsA and short-course methotrexate to prevent graft-versus-host disease (GVHD). CsA was started at 3.0 mg/kg/day and the dose was adjusted to maintain the blood CsA concentration between 250 and 350 ng/ml. The actual dose of CsA averaged 1.9 mg/kg/day at the 3rd week after transplantation. The incidence of grade II-IV acute GVHD was 29.9%. Patient age and sex were identified as independent significant risk factors for acute GVHD. The CsA concentration during the 3rd week after transplantation most strongly affected the incidence of grade II-IV acute GVHD (RR 0.995 for an increase in CsA concentration by 1 ng/ml, P = 0.037) adjusted for other risk factors. The incidence of acute GVHD was significantly lower in patients with a 3rd-week CsA concentration higher than 300 ng/ml than in those with values between 200 and 300 ng/ml (20% vs. 35%, P = 0.036). We concluded that the blood CsA concentration at peri-engraftment period may be important in preventing acute GVHD. Am. J. Hematol. 81:838-844, 2006. V V C 2006 Wiley-Liss, Inc.

Pharmacokinetics of CsA during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation

“…However, the dose, target blood level, and schedule of administration vary among protocols and have not been optimized. 1 It has been shown that the blood concentration of CsA affects the incidences of acute GVHD and adverse events, 2 and an increase in the target blood concentration from 300 to 500 ng/ml in the continuous infusion of CsA significantly decreased the incidence of acute GVHD. 3 On the basis of these results, we are currently administering CsA by continuous infusion with target concentrations of 500 ng/ml for standard-risk patients and 300 ng/ml in highrisk patients.…”

Effect of Posaconazole on Cyclosporine Blood Levels and Dose Adjustment in Allogeneic Blood and Marrow Transplant Recipients

“…It is noteworthy that the posaconazole prescribing information also includes a recommendation for upfront reduction of the dose of CsA upon initiation of combined treatment (17), which emerged from a very small study of cardiac transplantation (16) and has never been analyzed in allo-BMT recipients. In these patients, the potential occurrence of subtherapeutic blood CsA levels, even transiently, has a strong negative impact on GVHD and on the outcome of allo- BMT (5,6,11,12,14,19). The clinical need for such an upfront CsA dose reduction in patients starting posaconazole in this clinical setting ought to be studied.…”

“…Unfortunately, levels were assessed only twice, at the baseline and 2 weeks from the start of combined treatment, and neither earlier time points nor the need for upfront dose adjustment was analyzed. From 1988, when Yee et al first reported a significant association between low trough CsA concentrations and the risk of developing acute GVHD the following week (19), it is well established that subtherapeutic CsA levels after allo-BMT have a negative impact on transplant outcome (5,6,11,12,14). In order to avoid such subtherapeutic CsA levels, even transiently, general practice developed to widely accept that in the absence of toxicity, high blood CsA levels up to twice the upper limit of the therapeutic range would not require a dose reduction (1).…”

A Comparison of Tacrolimus and Cyclosporine for Graft-Versus-Host Disease Prophylaxis after Peripheral Blood Stem Cell Transplantation from HLA-Identical Sibling Donors

“…Several cyclosporine administration protocols, including continuous infusion and higher target trough concentrations, are used. [13][14][15] Our method was considered a GVHD prophylaxis with a standard cyclosporine administration protocol during the time period included in this study;…”