Cyclosporine A (CsA) 2-h concentrations vary between patients without correlation to graft-versus-host disease after allogeneic haematopoietic stem cell transplantation.
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 > 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 > or = 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.
Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden. lisbeth.barkholt@karolinska.se
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Barkholt
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Remberger
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Bodegård
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Ringdén
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Y
Böttiger
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D007700:Kinetics; D007938:Leukemia / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine