Li Fei, Yi Shu-hua, Yu Zhen, Xing Li-jie, Xu Yan, Qi Jun-yuan, Zhao Yao-zhong, Li Zeng-jun, Qiu Lu-gui
Institute of Hematology and Blood Diseases Hospital, CAMS & PUMC, State Key Laboratory of Experimental Hematology, Tianjin 300020, China.
Zhonghua Xue Ye Xue Za Zhi. 2013 May;34(5):383-8. doi: 10.3760/cma.j.issn.0253-2727.2013.05.002.
To evaluate the efficacy and safety of a chemoimmunotherapy regimen of rituximab, fludarabine and cyclophosphamide (FCR) for patients with chronic lymphocytic leukemia(CLL).
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.
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.
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.
评估利妥昔单抗、氟达拉滨和环磷酰胺（FCR）化疗免疫治疗方案对慢性淋巴细胞白血病（CLL）患者的疗效和安全性。
回顾性分析2003年4月至2012年1月在我院接受FCR方案治疗的26例CLL患者的临床资料。根据Rai风险分层、β₂微球蛋白（β₂-MG）、乳酸脱氢酶（LDH）、ζ链相关蛋白70（ZAP-70）、CD38、细胞遗传学和免疫球蛋白重链可变区基因（IgVH）突变状态等指标对患者进行分组。评估治疗疗效和生存率，并评估FCR方案的安全性。
26例患者中，总缓解率（ORR）为76.9%，10例（38.5%）达到完全缓解（CR），10例（38.5%）部分缓解（PR）。中位随访时间为30（3 - 98）个月，所有患者的中位无进展生存期（PFS）估计为42（16 - 68）个月，中位总生存期（OS）为63（41 - 85）个月。与较高CR率相关的临床参数为既往治疗方案＜2疗程、FCR 2疗程后骨髓淋巴细胞比例下降≥50%、低LDH、低β₂-MG和ZAP-70阴性（回顾性分析，P = 0.014、0.008、0.027、0.035和0.013）。微小残留病（MRD）阴性、LDH正常且FCR 2疗程后骨髓淋巴细胞比例下降≥50%的患者的PFS和OS时间显著优于对照组（P＜0.05），非高危遗传学组的PFS显著优于高危遗传学组（P = 0.005），而两组间的OS无统计学显著差异。最常见的毒性反应为胃肠道反应（88.5%），其次是骨髓抑制（80.8%）：包括中性粒细胞减少、贫血和血小板减少。感染占30.8%，主要为肺部感染。
FCR是治疗CLL患者的一种有效且耐受性良好的疗法。MRD阳性、LDH升高、FCR 2疗程后骨髓淋巴细胞比例下降＜50%的患者以及高危遗传学患者在取得治疗反应后适合采用更有效的治疗。
