Dasatinib (SPRYCEL®, BMS-354825) is a multi-targeted kinase inhibitor of BCR-ABL with significant activity in CML after imatinib failure. Dasatinib is well tolerated. The most frequent non-hematologic toxicities are gastrointestinal, rash, and fluid retention syndromes. We evaluated the incidence and outcome of pleural effusion among 131 pts with CML treated in phase I (n=50) and II (n=81) studies of dasatinib after imatinib failure or intolerance at our institution. The median age was 59 years (range, 19 to 81). Sixty-one (47%) pts were in chronic (CP), 30 (23%) in accelerated (AP), and 40 (30%) in blast phase (BP). The daily dose of dasatinib was 140 mg in 9 (7%; 6 bid, 3 qd). Dasatinib was administered for a median of 42 wks (range, 4 to 120 wks). Pleural effusion occurred in 41 (31%) pts; it was grade 3–4 in 17 (13%). The median time to its development was 5 wks (range, 1 to 107). Effusion occurred in 34% of pts in CP, 34% in AP, and 32% in BP. Effusions were categorized according to the volume of lung involvement: grade 1 ( 76%) in 1 (2.5%; 0.7% of total) pt. Grade ≥ 3 effusion occurred in 6 pts with CP and in 11 with advanced phase CML (5 AP, 6 BP). Effusion was more frequent among pts receiving daily doses ≥ 140 mg compared to those treated at