Objective: To analyze the survival and first-line immune-chemotherapy (CIT) of chronic lymphocytic leukemia (CLL) with abnormal TP53 gene in the era of traditional CIT. Methods: The clinical data of 118 CLL patients diagnosed from January 2003 to August 2017 were collected. Survival was analyzed according to indicators including sex, age, Binet risk stratification, B symptoms, β(2)-microglobulin (β(2)-MG) , immunoglobulin heavy chain variable region gene (IGHV) mutation status, chromosome karyotype and TP53 gene deletion/mutation. The efficacy of first-line CIT of 101 CLL patients was further analyzed. Results: Among 118 patients, median progression-free survival (PFS) was 12 (95%CI 10.148-13.852) months and median overall survival (OS) was 53 (95%CI 41.822-64.178) months, only 30.5% patients survived over 5 years. Low β(2)-MG<3.5 mg/L indicated longer PFS (P=0.027) , female and Binet A patients had longer OS (P=0.011 and 0.013, respectively) . Of 118 patients, 17 (14.4%) didn't receive any therapy until follow-up time or the dead time. Among the 101 patients who received ≥1 CIT, median time to first treatment (TTFT) was 1 (0-62) months, patients in Binet A had longer TTFT (P<0.001) compared to the patients in Binet B/C. According to statistical needs, we divided those first-line CIT into four groups: there were 30 cases (29.7%) in mild chemotherapy group (mainly treated with nitrogen mustard phenylbutyrate or rituximab alone) , 32 cases (31.7%) in the fludarabine-containing group, 23 cases (22.8%) in high-dose methyprednisolone (HDMP) containing group and 16 cases (15.8%) in the other chemotherapy group. The first regimen contained HDMP can bring longer PFS (P<0.001) , however the OS between four groups had no statistical differences. Conclusion: CLL patients with abnormal TP53 gene had poor response to immunotherapy, rapid clinical progressing, first-line immunotherapy containing HDMP can prolong PFS and will create an opportunity for patients to participate in clinical trials of novel drugs.
目的: 分析传统免疫化疗(CIT)时代,TP53基因异常[TP53缺失和(或)突变]慢性淋巴细胞白血病(CLL)患者一线CIT疗效及生存情况。 方法: 收集2003年1月至2017年8月在江苏省人民医院血液科诊断的118例TP53异常CLL患者基线资料[性别、年龄、分期、B症状(发热、盗汗、体重减低)、β(2)微球蛋白(β(2)-MG)、免疫球蛋白重链可变区(IGHV)突变状态、染色体核型、一线CIT]进行生存分析,分析101例接受一线CIT患者的疗效。 结果: 118例CLL患者均通过电话、门诊及住院等方式随访至2018年3月10日,中位无进展生存(PFS)时间为12(95%CI 10.148~13.852)个月,中位总生存(OS)时间为53(95%CI 41.822~64.178)个月。分析患者基线资料对患者生存影响,β(2)-MG<3.5 mg/L患者具有较长的PFS时间(P=0.027),女性患者以及Binet A期患者具有更长OS时间(P=0.011)。118例患者中,有17例(14.4%)自诊断至死亡/随访终点未接受任何抗肿瘤治疗,101例接受了一线及以上的CIT(85.6%),中位至首次治疗时间(TTFT)仅为1(0~62)个月,Binet A期较Binet B/C期患者具有更长TTFT(P<0.001)。进一步分析101例患者初治方案,按治疗方案分为四组,分别是温和治疗组(主要为单用苯丁酸氮芥或单用利妥昔单抗治疗)30例(29.7%),含氟达拉滨化疗组32例(31.7%),含大剂量激素化疗组23例(22.8%),其他化疗组16例(15.8%)。含大剂量激素化疗方案可获得较长PFS时间(P<0.001),四组间OS差异无统计学意义。 结论: TP53基因异常的CLL患者对免疫化疗反应差,临床进展迅速,一线使用含大剂量激素方案化疗可以延长PFS时间,为患者后续加入复发难治新药临床试验创造机会。.
Keywords: Abnormal TP53 gene; Complex karyotype; Immunotherapy; Leukemia, lymphocytic, chronic.