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Toxic absorption of pimecrolimus in a patient with severe acute graft-versus-host disease

Bone Marrow Transplantation volume 36, pages 919–920 (2005)Cite this article

A Corrigendum to this article was published on 21 June 2006

Acute graft-versus-host disease (GVHD) is an immunologically mediated disease that continues to be a significant complication of allogeneic bone marrow transplantation. An erythematous, maculopapular rash is often the first sign that donor engraftment has occurred, and is associated with a graft-versus-leukemia (GVL) effect (for review Zeiser et al1). GVHD, GVL, and the associated cytokines may help drive sustained donor engraftment, particularly in patients who have previously rejected an allogeneic graft. Where a strong GVL is needed for an anti-tumor effect and GVHD is desired to promote sustained engraftment, strategies to allow the desired immune response to continue while tempering undesired toxicity to the patient are often attempted. These strategies may include topical application of drugs, under the assumption that there will be only local, not systemic, absorption. We report the first case of significant systemic absorption of a topical medication in cutaneous acute GVHD, and advise that care be taken when administering topical medications to patients with cutaneous GVHD.

A white male, 2 years 8 months old, underwent matched unrelated donor bone marrow transplantation for X-linked autoimmunity allergic dysregulation syndrome (XLAAD) (reviewed in Ferguson et al2). He had developed insulin-dependent diabetes mellitus, atopic dermatitis, and multiple food allergies within the first year of life. XLADD is a life-threatening, inherited disorder that also afflicted his older sibling and two maternal first cousins (details of the cases and their transplant course are reported separately). His brother and maternal cousin previously had difficulties with an ablative bone marrow transplant and needed donor lymphocyte infusion (DLI) and GVHD to achieve full donor engraftment. Therefore, the patient underwent matched-unrelated allogeneic BMT with a nonmyeloblative regimen of antithymocyte globulin (ATG), high-dose steroids, plasmapheresis, and post transplant DLI to boost engraftment, but he rejected the graft with demonstrable cytotoxic host-anti donor T lymphocytes. The patient underwent a second matched-unrelated donor BMT following a preparative regimen of cyclophosphamide and total-body irradiation, augmented with ATG and steroids followed by infusion of marrow from a second unrelated donor. Cyclosporine with short course methotrexate was given for GVHD prophylaxis.

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Authors and Affiliations

  1. School of Medicine, The Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA

    D L Neuman

  2. Pediatric Oncology Division, Department of Oncology, The Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA

    J E Farrar & M A Higman

  3. Division of Dermatopathology, Department of Dermatology, The Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA

    J M Moresi

  4. Department of Oncology, The Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA

    G B Vogelsang

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  1. D L Neuman
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  5. M A Higman
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Neuman, D., Farrar, J., Moresi, J. et al. Toxic absorption of pimecrolimus in a patient with severe acute graft-versus-host disease. Bone Marrow Transplant 36, 919–920 (2005). https://doi.org/10.1038/sj.bmt.1705146

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