Objective: To investigate the efficacy of fludarabine and cyclophosphamide combined with rituximab (FCR) in previously untreated patients with chronic lymphocytic leukemia (CLL) . Methods: The clinical data of 43 enrolled patients from May 2004 to December 2017 were analyzed the efficacy and survival results. Results: A total of 43 patients with 31 males and 12 females, and the median age was 58 years old (range 36 to72) before treatment. There were 8 patients with symptom B. The median number of peripheral blood lymphocyte was 26 (3-550) ×10(9)/L. IGHV unmutated was detected in 62.1% (18/29) patients, P53 deletion in 14% (6/43) patients, RB1 deletion in 18.6% (8/43) patients, Trisomy 12 in 25.6% (11/33) patients, ATM deletion in 16.7% (7/42) patients, respectively. The median number of treatment courses administered was 4 (range 2-6) . Twenty patients obtained CR (46.5%) , 18 patients obtained PR, 4 patients were SD, 1 patient was PD. The overall response rate (ORR) was 88.37%. Seven patients obtained MRD negative. After the median follow-up time of 51 (6-167) months, median PFS was 67 (29-105) months, median OS was not reach, 5-year PFS was (62.1±8.6) %, 10-year PFS was (31±14.3) %, 5-year OS was (70.5±8.3) %, and 10-year OS was (51.3±13.8) %. Less than 4 courses predicted adverse OS (P<0.05) . P53 deletion and less than 4 courses were associated with poor PFS (P<0.001) , and the prognostic value still remained after multivariate analysis[HR=7.65 (95%CI 1.74-33.60) , P=0.007; HR=3.75 (95%CI 1.19-11.80) , P=0.025]. Eighteen patients (41.9%) appeared grade 2-3 infection after chemotherapy, and 19 patients (44.2%) appeared grade 3-4 hematological adverse reactions. One patient (2.3%) was developed tumor lysis syndrome. All adverse reactions were controlled or recovered spontaneously. Conclusion: Previously untreated CLL patients treated with FCR had a high response rate and good survival rate, which is an important treatment choice for fit patients.
目的： 探讨FCR方案（氟达拉滨+环磷酰胺+利妥昔单抗）一线治疗慢性淋巴细胞白血病（CLL）的疗效。 方法： 回顾性分析2004年5月至2017年12月一线应用FCR方案治疗的43例CLL患者的临床资料。 结果： ①43例CLL患者中，男31例，女12例，接受FCR方案治疗时中位年龄58（36~72）岁；8例患者伴B症状，外周血中位淋巴细胞计数26（3~550）×10(9)/L，IGHV基因未突变62.1%（18/29），P53基因缺失14.0%（6/43），RB1基因缺失18.6%（8/43），12号染色体三体占25.6%（11/33），ATM基因缺失16.7%（7/42）。全部患者FCR方案中位疗程数为4（2~6）个。②全部43例患者的总体反应率（ORR）为88.4%（38/43），完全缓解（CR）20例（46.5%），部分缓解（PR）18例（41.9%），疾病稳定（SD）4例（9.3%），疾病进展（PD）1例（2.3%）；7例（16.3%）患者获得微小残留病（MRD）阴性。③中位随访51（6~167）个月，中位无进展生存（PFS）时间为67（29~105）个月，中位总生存（OS）时间未达到，5年PFS率为（62.1±8.6）%，10年PFS率为（31.0±14.3）%，5年OS率为（70.5±8.3）%，10年OS率为（51.3±13.8）%。疗程数<4为影响OS的不良预后因素，P53基因缺失、疗程数<4为影响PFS的不良预后因素（P<0.001），且在多因素分析中仍具有预后意义[P53基因缺失：HR=7.65（95%CI 1.74~33.60），P=0.007；疗程数<4：HR=3.75（95%CI 1.19~11.80），P=0.025]。④18例（41.9%）患者于化疗后发生2~3级感染，19例（44.2%）发生3~4级血液学不良反应，1例（2.3%）患者发生肿瘤溶解综合征，所有不良反应经对症处理均恢复。 结论： FCR方案一线治疗CLL的治疗反应及远期生存较理想，不良反应可接受。.
Keywords: Cyclophosphamide; Fludarabine; Leukemia, lymphocytic, chronic; Rituximab; Treatment outcome.