title: Fatal vascular leak syndrome with extensive hemorrhage, peripheral neuropathy and reactive erythrophagocytosis: an unusual complication of recombinant IL-3 therapy.
abstract: A 39-year-old patient with severe aplastic anemia (AA), resistant to therapy, 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 culminating in complete paralysis. She died 25 days after beginning treatment from profuse bleeding. On autopsy, evidence of vascular leaks with widespread bleeding and extensive hemorrhagic involvement of peripheral nerves was found. An additional feature was massive reactive erythrophagocytosis in lymph nodes, spleen and bone marrow. The coincidence between rhIL-3 administration and the dramatic events suggest a causal relation. 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 major factor in the development of both a vascular leak and reactive erythrophagocytosis. This case report can be regarded as an example of the possible unusual pathologic phenomena we may expect to see in the near future with increasing use of growth factors.
authors.affiliation: Department of Pathology, Kantonspital, University of Basel, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Hurwitz
authors.forename: A
authors.initials: A
authors.lastname: Probst
authors.forename: G
authors.initials: G
authors.lastname: Zufferey
authors.forename: A
authors.initials: A
authors.lastname: Tichelli
authors.forename: M
authors.initials: M
authors.lastname: Pless
authors.forename: L
authors.initials: L
authors.lastname: Kappos
authors.forename: B
authors.initials: B
authors.lastname: Speck
authors.forename: A
authors.initials: A
authors.lastname: Gratwohl
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000473:pathology; D004487:Edema / Q000473:pathology; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D007377:Interleukin-3 / Q000009:adverse effects*; D008198:Lymph Nodes / Q000473:pathology; D009422:Nervous System Diseases / Q000139:chemically induced*; D011994:Recombinant Proteins
chemical_list: D007377:Interleukin-3; D011994:Recombinant Proteins