1. ¹Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
2. ²Department of Clinical Immunology, Division of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden
3. ³Department of Clinical Pharmacology, Division of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden

Correspondence: Dr L Barkholt, Centre for Allogeneic Stem Cell Transplantation B87, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm SE-141 86, Sweden. E-mail: lisbeth.barkholt@karolinska.se

Received 7 December 2006; Revised 7 June 2007; Accepted 14 June 2007; Published online 30 July 2007.

Abstract

Cyclosporine A (CsA) therapy based on 2-h concentrations (C2) after oral administration has demonstrated low acute rejection rates after solid organ transplantation. We analysed the correlation between C2 and trough (C0) levels of oral CsA therapy in samples obtained twice in consecutive weeks from 58 patients during their first admission for allogeneic haematopoietic stem cell transplantation. Also 8-h concentration curves were obtained from 23 patients. The mean (range) CsA dose was 332 (167–763) and 255 (113–575) mg/day for patients with matched unrelated donor (MUD) and human leukocyte antigen identical sibling donor (Sib), respectively. Median (range) C0 and C2 were 254 (145–332) and 898 (419–1466) ng/ml in MUD patients, and 130 (93–265) and 554 (196–988) ng/ml in Sib patients. In MUD patients with either aGVHD grade <II or II, the median C2 were 915 (419–1466) and 890 (519–1399) ng/ml, respectively. In Sib patients with aGVHD grade <II or grade II, the median C2 were 552 (404–718) and 539 (196–988) ng/ml, respectively. The median C2 levels were comparable in patients with or without severe infections. Interindividual variations in CsA uptake and metabolism may explain the wide variation of C2 levels without prediction for increased risk for severe aGVHD or infectious complication when C0 guided the CsA dosing.