Successful treatment using tacrolimus ointment for cutaneous graft-versus-host disease

Abstract

Graft-versus-host disease (GVHD) is a well-known complication of allogeneic stem cell transplantation (allo-SCT). GVHD occurs when transplanted donor T cells react to foreign host cells, causing damage to a wide variety of host tissues. GVHD damage that is multi-organic is treated mainly with systemic cyclosporine, steroids, and other immunosuppressive agents. GVHD that manifests as only limited skin involvement can be treated topically, avoiding the severe side effects of the various systemic treatment options [1]. Although topical steroid therapy is the mainstay local treatment for cutaneous GVHD, its use is limited by adverse effects, including skin atrophy, telangiectasia, and striae cutis distensae, and therefore alternative approaches are being explored. Recently, topical tacrolimus has been used successfully in the treatment of chronic cutaneous GVHD [2, 3]. Here we report a case of severe acute cutaneous GVHD that was treated with tacrolimus ointment. A 50-year-old Japanese man was diagnosed with acute monocytic leukemia, or according to the French–American–British classification, acute myeloid leukemia (AML) M5b, with chromosomal abnormality of trisomy 8. The patient was treated with induction therapy for AML and achieved a partial remission. He then underwent an allogeneic bone marrow transplantation (BMT) from an HLA-matched unrelated donor. The conditioning regimen prior to BMT consisted of cyclophosphamide 60 mg/kg for 2 days and 8 Gy of total body irradiation. A combination of tacrolimus and short-term methotrexate was prescribed as prophylaxis for GVHD. At 11 days after BMT, the bone marrow engrafted and the patient presented with a high grade fever, elevated liver enzymes, and skin rash with erythema developed bilaterally on his arms and body. A skin biopsy revealed acute GVHD. Prednisone therapy was started at a dosage of 1 mg/kg, 70 mg/day. The symptoms of acute GVHD disappeared by day ?26. At day ?35, however, the patient had flaring and generalization of cutaneous GVHD without gastrointestinal or hepatic involvement of the disease. Prednisone at 60 mg/day and tacrolimus therapy were continued, and he received topical steroid therapy. Because the cutaneous GVHD remained, an evaluation of the effect of tacrolimus ointment on the affected area in comparison with steroid ointment only was discussed with the patient and, after obtaining written informed consult, he was instructed to apply 0.1% tacrolimus ointment once daily to the affected area on the left side, and only steroid ointment to the affected area on the right side. After 2 weeks of using tacrolimus ointment, his skin itch and redness on the left side were greatly reduced. Physical examination revealed a marked reduction in the amount of erythema, most notably on his thigh (Fig. 1). Skin biopsies were performed at day ?55 for the pathologic evaluation of the efficacy of tacrolimus ointment for cutaneous GVHD. The histologic and immunofluorescent findings from the right side, which was treated with control steroid ointment only, showed lymphocyte infiltration of the epithelium lesions with CD 8-positive T cells. In contrast, the findings from the left side, treated with tacrolimus ointment, showed no signs of GVHD (Fig. 2). Because the benefit of tacrolimus therapy was greater than that of the control steroid ointment, tacrolimus ointment was prescribed for both sides of his body. After 2 weeks, the skin redness was greatly reduced bilaterally. A. Kunitomi (&) H. Iida Y. Kamiya M. Hayashi H. Sao Department of Hematology, Meitetsu Hospital, 2-26-11 Sakoh, Nishi-ku, Nagoya 451-8511, Japan e-mail: akunitom@mx5.suisui-w.ne.jp