A phase II study of sequential combination chemotherapy with cyclophosphamide, prednisone, and 2-chlorodeoxyadenosine in previously untreated patients with chronic lymphocytic leukemia

• Published in: Leukemia Vol. 15; no. 8; pp. 1171 - 1175
• Main Authors: TEFFERI, A, LI, C-Y, SCHAEFER, P. L, MAILLIARD, J. A, REEDER, C. B, GEYER, S. M, ALLMER, C, LEVITT, R, MICHALAK, J. C, ADDO, F, KROOK, E, WITZIG, T. E
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-08-2001; Nature Publishing Group
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Biological and medical sciences; Chemotherapy; Chlorambucil; Chronic lymphocytic leukemia; Cladribine - administration & dosage; Clinical trials; Cyclophosphamide; Cyclophosphamide - administration & dosage; Disease-Free Survival; Drug therapy; Drug therapy, Combination; Durability; Female; Follow-Up Studies; Genetic aspects; Health aspects; Humans; Intravenous administration; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - mortality; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphatic leukemia; Male; Management; Medical sciences; Middle Aged; Minimal residual disease; Nucleoside analogs; Pharmacology. Drug treatments; Prednisone; Prednisone - administration & dosage; Remission; Remission (Medicine); Remission Induction; Survival; Toxicity; United States; Antineoplastic agent; Human; Corticosteroid; Drug combination; Purine nucleoside; Malignant hemopathy; Prednisone; Deoxyribonucleoside; Chemotherapy; Chronic; Cyclophosphamide; Chronic lymphocytic leukemia; Oxazaphosphinane derivatives; Treatment; Sequential; Lymphoproliferative syndrome; Nitrogen mustard; Cladribine; Phase II trial
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2402172

In an earlier study of previously untreated patients with chronic lymphocytic leukemia (CLL), we used a concomitant combination of chlorambucil and 2-chlorodeoxyadenosine and reported overall (OR) and complete (CR) remission rates of 80% and 20%, respectively. After a median follow-up of 5 years, more than 80% of the responders have had a relapse. In the current phase II study of 27 previously untreated patients with CLL, we used a sequential combination of six cycles of intravenous cyclophosphamide (1 g/m2) plus oral prednisone (100 mg/m2 per day for 5 days) followed by two to six cycles of 2-chlorodeoxyadenosine (5 mg/m2 per day for 5 days). The OR and CR rates were 96% and 33%, respectively. After a median follow-up of 29 months, 35% of the responders have had a relapse. Progression-free survival was significantly better in CR patients than in those with partial remission. However, minimal residual disease was phenotypically detected in four of the nine CR patients. Despite the fact that the current OR and CR rates are superior to those seen in a historical cohort treated with a concomitant schedule, a longer follow-up period is needed to assess the durability of these remissions, and a controlled trial is necessary to estimate the impact on overall survival and toxicity.