传统免疫化疗时代118例TP53基因异常慢性淋巴细胞白血病患者生存分析

Survival analysis of 118 chronic lymphocytic leukemia patients with abnormal TP53 gene in the era of traditional immunochemotherapy

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)、β2微球蛋白(β2-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%CI10.148~13.852)个月,中位总生存(OS)时间为53(95%CI41.822~64.178)个月.分析患者基线资料对患者生存影响,β2-MG<3.5 mg/L患者具有较长的PFS时间(P=0.027),女性患者以及BinetA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,BinetA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.

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,[β2-microglobulin(β2-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.Lowβ2-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.