Pulmonary infiltrates after cytokine therapy for stem cell transplantation- Massive deposition of eosinophil major basic protein detected by immunohistochemistry

Interleukin-2 (IL-2), a product of activated T-cells, is now being used in a number of protocols for cancer immunotherapy. In one stem cell transplant ation protocol for breast cancer, IL-2 is used together with interferon-gam ma (IFN-gamma) and cyclosporine to stimulate a graft-versus-tumor response and improve the likelihood of a prolonged remission. We present the case of a patient who developed peripheral eosinophilia, perihilar infiltrates, an d hypoxemia after autologous stem cell transplantation and the use of recom binant IL-2 and IFN-gamma. Histologic analysis of transbronchial lung biops ies demonstrated a few eosinophils within the bronchial submucosa. Immunost aining using antibodies directed against eosinophil major basic protein (MB P), however, revealed massive extracellular deposition of this toxic granul e protein throughout the lung parenchyma. IL-2 therapy is well known to ind uce a peripheral eosinophilia and to be associated with the capillary leak syndrome characterized by weight gain, edema, and oliguria. The findings no ted in this case report suggest that the eosinophil activation that accompa nies immunologic therapy with IL-2 can result in direct toxicity to the lun g and a localized vascular leak syndrome. This syndrome should be considere d in the differential diagnosis of pulmonary infiltrates that occur acutely after bone marrow transplantation with cytokine augmentation.