Therapy with daunomycin in chronic lymphoproliferative diseases

Abstract

Daunomycin was administered to 16 patients with chronic lymphoproliferative disorders (10 with Stage IV lymphoreticular sarcomas and 6 with chronic lymphocytic leukemia). The age of subjects was ranging between 36 and 64 years (average 54 years). 8 out of 16 patients had been previously treated with radiotherapy and/or chemotherapy. The drug was injected intravenously at the initial dose of 0.6 mg/kg (7 cases), 0.8 mg/kg (8 cases) and 1 mg/kg (1 case) for 3–4 consecutive days. After 1 day interval, treatment was continued in most cases on alternate days schedule until signs of toxicity appeared. In some patients after the initial course the dose/kg was increased or decreased according to the peripheral blood picture. The total dose ranged between 2.2 to 13.3 mg/kg. In 7 patients prednisone (50 mg daily by mouth) was given in association to daunomycin (tables 1 and 2). Objective responses were seen in 5 out of 6 patients with chronic lymphocytic leukemia. While a consistent shrinkage of the nodes and especially of the spleen was observed in all responsive cases, the fall in the leukocyte level was mild and transient. In lymphoreticular sarcomas 5 out of 10 patients responded; the most significant regression was obtained in patients with splenomegaly, but also lymphonodes, hepatomegaly, pulmonary and cutaneous lesions responded. Two patients had also the bone marrow infiltrated with extrinsic cells: no significant changes were seen after treatment with 6 and 6.2 mg/kg. Regression usually occurred after few doses; nevertheless in all but one responsive patients they were incomplete. Maintenance treatment was then started with alkylating agents. The patients treated with daunomycin and prednisone did not show any better response than those treated with daunomycin alone. In 5 cases a sudden dyspnea, tachycardia and hypotension developed after different doses of daunomycin ranging from 2.2 to 8 mg/kg. Four patients died within 24 hours and one after 5 days from the beginning of symptoms. EKG abnormalities (tachicardia, flattening of ST and T waves) were recorded in all patients died with cardiac failure. In two cases the EKG changes appeared only after daunomycin administration while in three cases mild electric abnormalities present before the treatment got worse after few doses of daunomycin. Necroscopy was performed only in one case where besides superficial necrosis of the intestinal mucosa no specific alterations of the heart and vessels were seen. The conclusion is that daunomycin can produce rapid objective responses in chronic lymphoproliferative disorders, although the quality of these regressions in the majority of patients is insufficient to influence the natural course of the disease. Prolongued administration of the drug especially in patients previously treated with chemotherapy is not recommended because of the severe marrow depression. The so-called cardiac toxicity seems from this study to be dose-indipendent in patients with cardiovascular disease and EKG abnormalities before drug administration. Daunomycin therefore should not be given even in small dosage to patients with EKG abnormalities.