FATAL VASCULAR LEAK SYNDROME WITH EXTENSIVE HEMORRHAGE, PERIPHERAL NEUROPATHY AND REACTIVE ERYTHROPHAGOCYTOSIS - AN UNUSUAL COMPLICATION OFRECOMBINANT IL-3 THERAPY

A 39-year-old patient with severe aplastic anemia (AA), resistant to t herapy, received recombinant human IL-3 (rhIL-3) on a phase I/II trial . During treatment she developed disseminated skin lesions, suggestive of vasculitis, and severe progressive peripheral neuropathy culminati ng in complete paralysis. She died 25 days after beginning treatment f rom profuse bleeding. On autopsy, evidence of vascular leaks with wide spread bleeding and extensive hemorrhagic involvement of peripheral ne rves was found. An additional feature was massive reactive erythrophag ocytosis in lymph nodes, spleen and bone marrow. The coincidence betwe en rhIL-3 administration and the dramatic events suggest a causal rela tion. As a possible pathogenic mechanism, an rhIL-3 induced excessive stimulation of macrophages and production of secondary cytokines such as tumor necrosis factor (TNF) is suggested. TNF is considered as a ma jor factor in the development of both a vascular leak and reactive ery throphagocytosis. This case report can be regarded as an example of th e possible unusual pathologic phenomena we may expect to see in the ne ar future with increasing use of growth factors.