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Alterations in pulmonary function in cancer patients receiving adoptive immunotherapy with tumor-infiltrating
D S Lazarus1, J T Kurnick, R L Kradin
1Department of Medicine, Massachusetts General Hospital, Boston 02114.
Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) is currently being investigated in the treatment of chemoresistant cancers. In protocols using high dosages of IL-2 and adoptive transfers of lymphokine-activated killer (LAK) cells, severe pulmonary toxicities, including pulmonary edema and respiratory failure, are regularly observed. Serial measurements of pulmonary function in patients receiving TIL and continuous infusions of moderate dosages of IL-2 showed the development of mild obstructive and restrictive defects. Partial reversibility of the FEV1 with bronchodilators was observed, suggesting the development of hyperreactive airways. Decreases in lung volumes, DLCO, and gas exchange occurred and may reflect pulmonary infiltration by inflammatory cells, increased lung water, or diminished chest wall function. We conclude that adoptive immunotherapy with TIL and IL-2 produces changes in systemic immune response that may contribute to abnormal pulmonary physiology.
Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) is currently being investigated in the treatment of chemoresistant cancers. In protocols using high dosages of IL-2 and adoptive transfers of lymphokine-activated killer (LAK) cells, severe pulmonary toxicities, including pulmonary edema and respiratory failure, are regularly observed. Serial measurements of pulmonary function in patients receiving TIL and continuous infusions of moderate dosages of IL-2 showed the development of mild obstructive and restrictive defects. Partial reversibility of the FEV1 with bronchodilators was observed, suggesting the development of hyperreactive airways. Decreases in lung volumes, DLCO, and gas exchange occurred and may reflect pulmonary infiltration by inflammatory cells, increased lung water, or diminished chest wall function. We conclude that adoptive immunotherapy with TIL and IL-2 produces changes in systemic immune response that may contribute to abnormal pulmonary physiology.
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