Objective: To evaluate the efficacy and safety of a chemoimmunotherapy regimen of rituximab, fludarabine and cyclophosphamide (FCR) for patients with chronic lymphocytic leukemia(CLL).
Methods: The clinical data of 26 CLL patients receiving FCR regimen in our hospital from April 2003 to January 2012 were analyzed retrospectively. Patients were grouped according to indicators including Rai risk stratification, β(2)-MG, LDH, ZAP-70, CD38, cytogenetics and immunoglobulin heavy chain variable region gene (IgVH) mutation status. Therapy efficacy and survival were evaluated and the safety of FCR regimen was assessed.
Results: Among 26 patients, the overall response rate ( ORR ) was 76.9%, 10 patients (38.5%) achieved complete remission(CR) and 10(38.5%) partial remission(PR). With a median follow-up time of 30 ( 3-98 ) months, the median estimated progression-free survival(PFS) for all patients was 42(16-68) months and median overall survival(OS) was 63(41-85)months. Clinical parameters associated with higher CR rates were ＜2 courses of prior treatment regimens, proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR, low LDH, low β(2)-MG and ZAP-70 negative (P = 0.014, 0.008, 0.027, 0.035 and 0.013, retrospectively). PFS and OS time in minimal residual disease(MRD)-negative, normal LDH and proportions of bone marrow lymphocytes declining ≥ 50% after 2 courses of FCR patients were significantly better than that of the control group (P＜0.05), PFS in the non-high-risk genetics group was significantly better than that in the high-risk genetics group (P = 0.005), while OS between two groups showed no statistically significant difference. The most common toxicities were gastrointestinal reactions (88.5%), followed by bone marrow suppression (80.8%): including neutropenia, anemia and thrombocytopenia. Infections accounted for 30.8%, mainly lung infection.
Conclusion: FCR is an effective and well-tolerated therapy for patients with CLL. Patients with MRD-positive, elevated LDH, proportions of bone marrow lymphocytes declining＜50% after 2 courses of FCR and high risk genetics patients are suitable for more effective treatment after achieving treatment response.
目的 评价利妥昔单抗联合氟达拉滨和环磷酰胺（FCR）方案治疗慢性淋巴细胞白血病（CLL）的疗效和安全性。方法 回顾性分析2003年4月至2012年1月应用FCR方案治疗的26例CLL患者病例资料。根据患者的Rai危险度分层、β2-微球蛋白（β2-MG）、LDH、ZAP-70表达、CD38表达、细胞遗传学和免疫球蛋白重链可变区基因（IgVH）突变状态等指标进行分组，行疗效和生存分析。同时评价FCR方案的安全性。结果 26例患者完全缓解（CR）10例（38.5%），部分缓解（PR）10例（38.5%），总反应率（ORR）76.9%。中位随访30（3~98）个月，中位无进展生存（PFS）时间 42(16～68)个月，总生存（OS）时间63(41～85)个月。曾治疗疗程数＜2个、2个疗程骨髓淋巴细胞比例下降≥50%、低LDH、低β2-MG和ZAP-70阴性与高CR率相关（P值分别为0.014、0.008、0.027、0.035和0.013）。微小残留病（MRD）阴性、LDH正常和2个疗程骨髓淋巴细胞比例下降≥50%的患者PFS时间和OS时间明显优于相应对照组（P值均＜0.05），非遗传学高危组患者PFS时间优于遗传学高危组患者（P=0.005），OS时间差异无统计学意义。FCR方案的主要不良反应为胃肠道反应（88.5%）；其次为骨髓抑制（80.8%），包括中性粒细胞减少、贫血和血小板减少；感染发生率为30.8%，主要为肺部感染。结论 FCR方案是治疗CLL患者的一种有效而安全的方案。MRD阳性、LDH升高、2个疗程骨髓淋巴细胞比例下降＜50%和高危遗传学异常患者应在获得治疗反应后尽快寻求更加有效的治疗方案。