Bosch Francesc, Ferrer Ana, Villamor Neus, González Marcos, Briones Javier, González-Barca Eva, Abella Eugenia, Gardella Santiago, Escoda Lourdes, Pérez-Ceballos Elena, Asensi Antoni, Sayas Ma José, Font Llorenç, Altés Albert, Muntañola Ana, Bertazzoni Paola, Rozman María, Aymerich Marta, Giné Eva, Montserrat Emili
Department of Haematology, Hospital Clínic de Barcelona, Barcelona, Spain.
Clin Cancer Res. 2008 Jan 1;14(1):155-61. doi: 10.1158/1078-0432.CCR-07-1371.
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.
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. x 3 days, cyclophosphamide 200 mg/m(2) i.v. x 3 days, and mitoxantrone 6 mg/m(2) i.v. x 1 day. Treatment outcome was correlated with clinical and biological variables. The clinical significance of eradicating minimal residual disease (MRD) was also analyzed.
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.
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.
氟达拉滨、环磷酰胺和米托蒽醌（FCM）方案在既往治疗的慢性淋巴细胞白血病（CLL）患者中具有较高的缓解率。本研究旨在探讨FCM作为CLL一线治疗方案的疗效。
对69例65岁以下的活动性CLL患者进行治疗。患者接受六个周期的氟达拉滨25mg/m²静脉滴注，连续3天；环磷酰胺200mg/m²静脉滴注，连续3天；米托蒽醌6mg/m²静脉滴注，1天。治疗结果与临床和生物学变量相关。还分析了清除微小残留病（MRD）的临床意义。
总体缓解率、MRD阴性完全缓解（CR）率、MRD阳性CR率、结节性部分缓解（PR）率和PR率分别为90%、26%、38%、14%和12%。10%的患者发生严重（3或4级）中性粒细胞减少。分别有1%和8%的病例报告了严重感染和轻度感染。中位缓解持续时间为37个月。del(17p)患者未达到CR。达到MRD阴性CR的患者比缓解较差的患者缓解持续时间更长，总生存期也更长。低血清乳酸脱氢酶水平、低ZAP-70表达和IgV(H)基因突变预示着更长的缓解持续时间。最后，白血病细胞中低ZAP-70和CD38表达均与实现MRD阴性相关。
FCM在未经治疗的活动性CLL患者中诱导出较高的缓解率，包括MRD阴性CR。治疗毒性可接受。高ZAP-70和CD38表达增加均预示无法获得MRD阴性缓解。与缓解较差的患者相比，能够清除MRD的患者缓解持续时间更长，总生存期也更长。这些结果表明FCM可以成为CLL患者化疗免疫治疗的理想辅助方案。
