Thalidomide in children undergoing bone marrow transplantation: Series at a single institution and review of the literature

Thalidomide has one of the most notorious drug histories because of its ter atogenicity. Its widespread use in the 1960s led to a worldwide epidemic of phocomelia in inborns; this in turn led to its complete ban in most of the world. However, it has now been licensed for selected indications includin g graft-versus-host-disease (GVHD) after bone marrow transplantation, wasti ng associated with tuberculosis and human immunodeficiency virus infection, and leprosy. Little is known, however, about its use in children in these settings. Therefore, we report our experience and review the literature on thalidomide in children for GVHD after bone marrow transplantation. We stud ied 6 patients, 2 with chronic GVHD, 2 with acute GVHD, and 2 with acute GV HD progressing into chronic disease. One patient with chronic GVHD had a co mplete response, whereas the other had a partial response. Side effects con sisted primarily of sedation and constipation, which are reported previousl y and well known side effects. None had neuropathy. One patient had rash, e osinophilia, and early pancreatitis that began shortly after initiation of thalidomide, persisted, and resolved only after discontinuation of thalidom ide. Eosinophilia and pancreatitis are both previously unreported side effe cts or associated findings of thalidomide treatment. Review of the literatu re reveals three major studies of thalidomide in GVHD; of these two include d children and adults together, and one in which age range of patients was not mentioned. In addition, four series of children receiving only thalidom ide are reported. These series contained I to 14 patients each. Results show efficacy in at least 50% of children with chronic GVHD and lit tle or no efficacy in children with exclusively acute GVHD. Side effects ar e similar to those reported in adults and consisted mostly of sedation and constipation, both of which subsided over time and resolved after discontin uing the drug. We speculate on the reasons for which thalidomide is more ef fective in chronic, compared with acute, GVHD in children, and make recomme ndations for future study.