MYASTHENIA-GRAVIS IN ASSOCIATION WITH ALLOGENEIC BONE-MARROW TRANSPLANTATION - CLINICAL OBSERVATIONS, THERAPEUTIC IMPLICATIONS AND REVIEW OF LITERATURE

Myasthenia gravis (MG) is a rare complication of allogeneic bone marro w transplantation (BMT). We present the 11th case in the medical liter ature, a 23-year-old female 100 months post-allogeneic bone marrow tra nsplantation for acute myelogenous leukemia (AML). After discontinuati on of immunosuppression for chronic graft-versus-host disease (GVHD) i nvolving skin, gastrointestinal tract and lacrimal glands, the patient developed severe, progressive dysphagia initially attributed to esoph ageal candidiasis. With the development of muscle weakness, ptosis, an d dysphonia the diagnosis of generalized myasthenia gravis was suspect ed, and confirmed by elevated anti-acetylcholine receptor antibody tit er and a positive edrophonium challenge. Prednisone and pyridostigmine produced improvement, and thymectomy was performed without pathologic evidence of thymoma. Recurrent post-operative respiratory distress re quired transient mechanical ventilation. Twenty-seven months after dia gnosis, the patient requires maintenance prednisone to control symptom s of myasthenia gravis. The clinical features of all reported cases of MG post-allogeneic BMT are reviewed, and universal features include a n association with decreasing immunosuppression, the presence of other manifestations of chronic GVHD, anti-acetylcholine receptor antibodie s, and the absence of an associated thymoma. HLA Cw1, Cw7 and DR2 were identified at frequencies significantly above that expected from HLA antigen prevalance studies, and may be markers for increased risk of d eveloping MG post-allogeneic BMT. No statistically significant associa tions with HLA A2, B7, B35 or donor-recipient sex mismatch were presen t. Reinstitution of immunosuppression and standard therapies for myast henia gravis were effective in the majority of cases. The role of thym ectomy in this population remains unclear.