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Thirty-seven patients with Philadelphia-chromosone-positive (Ph′+) chronic myelogenous leukemia who were untreated or minimally pretreated were entered on the L-5 protocol. This protocol consisted of sequential treatment with splenic irradiation, splenectomy, arabinosylcytosine and 6-thioguanine, and L-asparaginase. Maintenance therapy was hydroxyurea or a multiple-drug regimen. The median survival of the 37 patients is 50 mo. Twelve patients showed a temporary reduction in the percentage of Ph′+ marrow metaphases to less than one-third of the initial values and in 7 of these patients none were found. The duration of the Ph′+ chromosome reduction ranged from 1 to 43 mo. The median survival of the responders has not yet been reached. It is concluded that whereas overall survival is not appreciably extended, patients who have a reduction in Ph′+ cells in the marrow may survive longer than the average; also, the reduction occurs most frequently in patients who have relatively small spleens at diagnosis. The reduction is difficult to maintain, and it may be reinduced in some patients with intensive chemotherapy.