AN APHYLACTIC REACTION TO CYCLOSPORIN IN A BONE MARROW TRANSPLANT RECIPIENT

Anaphylactic reactions to cyclosporin have been reported in renal transplant recipients (Kahn et al , 19 84; Leunissen et al. 198 5: Ptachcinski et ul, 19 8 5). However, to our knowledge no such reaction to a first exposure has previously been reported in bone marrow transplant recipients. Accordingly we would like to report the following case: A 5-year-old girl presented to us with lymphadenopathy, hepatosplenomegaly and bleeding. Her haemoglobin was 4.7 g/dl, white cell count 192 x 109/1 and platelet count 62 x l O / L 98% of the white cells were lymphoblasts of L2 FAB morphology and common acute lymphoblastic leukaemia immunological phenotype. She was entered on the United Kingdom Acute Lymphoblastic Leukaemia regimen X (IJKALL X) and full remission was documented 28 d later. Early intensification with daunorubicin, cytosine arabinoside, 6-thioguanine. epipodophyllotoxin and prednisolone was given. Two months later she was readmitted for an allogeneic bone marrow transplant from her histocompatible brother in view of the poor prognosis of her disease. The conditioning regimen included cyclophosphamide 60 mg/kg on two consecutive days arid total body irradiation (six fractions of 200 cGy over 3 d). Intravenous cyclosporiri infusion was started but after a few minutes she became acutely ill and developed an anaphylactic reaction with generalized cyanosis, hypotension (blood pressure 60 mmHg systolic), tachycardia of 1 54/ min, tachypnoea of 40/min and a generalized macular rash. The infusion was immediately discontinued followed by a prompt recovery. Thereafter prophylaxis against graft-versushost disease was carried out with methotrexate. Within 3 weeks the marrow had engrafted with chromosomally male cells but she died of infective complications 3 weeks later. This is the first case report of an anaphylactic reaction occurring during the first exposure to intravenous cyclosporin in a bone marrow transplant recipient. The infusion was made up with normal saline and mannitol neither of which is known to cause anaphylaxis. Recently Chapuis et al (1985) reported a similar incident. but this reaction occurred after multiple exposures to the drug and was thought to be due to the organic solvents used. The latter patient did not react to the oral preparation. We did not think it was feasible to challenge our patient with an oral dose because of the severity of her reaction and the fact that it occurred on first exposure. The suggestion put forward by Chapuis et al ( 1 985) does remain a possibility and further studies are needed to resolve the issue. This side effect has been reported to the Committee on Safety of Medicines in the U.K.