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Fludarabine, Cyclophosphamide, and Mitoxantrone as Initial Therapy of Chronic Lymphocytic Leukemia: High Response Rate and Disease Eradication
Ist Teil von
Clinical cancer research, 2008-01, Vol.14 (1), p.155-161
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2008
Quelle
MEDLINE
Beschreibungen/Notizen
Purpose: Fludarabine, cyclophosphamide, and mitoxantrone (FCM) results in a high response rate in previously treated patients with
chronic lymphocytic leukemia (CLL). The aim of this study was to investigate FCM as frontline therapy in CLL.
Experimental Design: Sixty-nine patients under the age of 65 years with active CLL were treated. Patients received six cycles of fludarabine 25
mg/m 2 i.v. × 3 days, cyclophosphamide 200 mg/m 2 i.v. × 3 days, and mitoxantrone 6 mg/m 2 i.v. × 1 day. Treatment outcome was correlated with clinical and biological variables. The clinical significance of eradicating
minimal residual disease (MRD) was also analyzed.
Results: The overall response, MRD-negative complete response (CR), MRD-positive CR, nodular partial response (PR), and PR rates were
90%, 26%, 38%, 14%, and 12%, respectively. Severe (grades 3 or 4) neutropenia developed in 10% of the patients. Major and
minor infections were reported in 1% and 8% of cases, respectively. Median response duration was 37 months. Patients with
del(17p) failed to attain CR. Patients achieving MRD-negative CR had a longer response duration and overall survival than
patients with an inferior response. Low serum lactate dehydrogenase levels, low ZAP-70 expression, and mutated IgV H genes predicted longer response duration. Finally, both low ZAP-70 and CD38 expression in leukemic cells correlated with
MRD-negativity achievement.
Conclusion: FCM induces a high response rate, including MRD-negative CRs in untreated patients with active CLL. Treatment toxicity is
acceptable. Both high ZAP-70 and increased CD38 expression predict failure to obtain MRD-negative response. Patients in whom
MRD can be eradicated have longer response duration and overall survival than those with inferior response. These results
indicate that FCM can be an ideal companion for chemoimmunotherapy of patients with CLL.