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Graft-versus-Host Disease

Cyclosporine A (CsA) 2-h concentrations vary between patients without correlation to graft-versus-host disease after allogeneic haematopoietic stem cell transplantation

Bone Marrow Transplantation volume 40, pages 683–689 (2007)Cite this article

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, the median C2 were 915 (419–1466) and 890 (519–1399) ng/ml, respectively. In Sib patients with aGVHD 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.

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Acknowledgements

This work has been supported by a grant from the National Network for Drug Development within The Foundation for Strategic Research, Sweden, and by the research funding of the Karolinska Institutet. We thank the patients and the staff at the Centre for allogeneic stem cell transplantation and the laboratory technicians at the Department of Clinical Pharmacology for compassionate and competent care of the patients, sample collection and analyse procedures. Novartis has generously contributed to cyclosporine A analyses by research funding, but has had no influence on the study protocol or preparation of this manuscript.

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Authors and Affiliations

  1. Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden

    L Barkholt & O Ringdén

  2. Department of Clinical Immunology, Division of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden

    L Barkholt, M Remberger, H Bodegård & O Ringdén

  3. Department of Clinical Pharmacology, Division of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden

    Y Böttiger

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Correspondence to L Barkholt.

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Barkholt, L., Remberger, M., Bodegård, H. et al. Cyclosporine A (CsA) 2-h concentrations vary between patients without correlation to graft-versus-host disease after allogeneic haematopoietic stem cell transplantation. Bone Marrow Transplant 40, 683–689 (2007). https://doi.org/10.1038/sj.bmt.1705788

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