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PURPOSE: In chronic lymphocytic leukemia (CLL), TP53 deletion/mutation is strongly associated with an adverse outcome and resistance to chemotherapy-based treatment. In contrast, TP53 defects are not associated with resistance to the anti-CD52 monoclonal antibody alemtuzumab or methylprednisolone. In an attempt to improve the treatment of TP53-defective CLL, a multicenter phase II study was developed to evaluate alemtuzumab and methylprednisolone in combination. PATIENTS AND METHODS: Thirty-nine patients with TP53-deleted CLL (17 untreated and 22 previously treated) received up to 16 weeks of treatment with alemtuzumab 30 mg three times a week and methylprednisolone 1.0 g/m(2) for five consecutive days every 4 weeks. Antimicrobial prophylaxis consisted of cotrimoxazole, itraconazole, and aciclovir (or valganciclovir for asymptomatic cytomegalovirus viremia). The primary end point was response as assigned by an end-point review committee. Secondary end points were safety, progression-free survival (PFS) and overall survival (OS). RESULTS: The overall response rate, complete response rate (including with incomplete marrow recovery), median PFS, and median OS were 85%, 36%, 11.8 months, and 23.5 months, respectively, in the entire cohort and 88%, 65%, 18.3 months, and 38.9 months, respectively, in previously untreated patients. Grade 3 to 4 hematologic and glucocorticoid-associated toxicity occurred in 67% and 23% of patients, respectively. Grade 3 to 4 infection occurred in 51% of the overall cohort and in 29% of patients less than 60 years of age. Treatment-related mortality was 5%. CONCLUSION: Alemtuzumab plus methypredisolone is the most effective induction regimen hitherto reported in TP53-deleted CLL. The risk of infection is age related and, in younger patients, seems only marginally higher than that associated with rituximab, fludarabine, and cyclophosphamide.

Original publication




Journal article


J Clin Oncol

Publication Date





1647 - 1655


Academies and Institutes, Adult, Aged, Aged, 80 and over, Alemtuzumab, Antibiotic Prophylaxis, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Disease-Free Survival, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Gene Deletion, Genes, p53, Humans, Kaplan-Meier Estimate, Leukemia, Lymphocytic, Chronic, B-Cell, Logistic Models, Male, Methylprednisolone, Middle Aged, Proportional Hazards Models, Remission Induction, Risk Assessment, Survival Rate, Treatment Outcome, United Kingdom