氟达拉滨和环磷酰胺联合利妥昔单抗（FCR方案）一线治疗慢性淋巴细胞白血病43例临床分析 Translated title: Clinical analysis of fludarabine and cyclophosphamide combined with rituximab in the first-line treatment of 43 cases of chronic lymphoblastic leukemia

Abstract

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。

Translated abstract

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.