Objective: To analyze the clinical characteristics of the patients with B-cell chronic lymphoproliferative disease（B-CLPD） in the new drug era and the effect of new drug treatment on efficacy and survival.
Methods: The clinical and laboratory data of 200 cases B-CLPD patients diagnosed between April 2015 and August 2021 were analyzed retrospectively. The clinical efficacy and survival of the patients under different treatments including Bruton tyrosine kinase（BTK） inhibitors， rituximab， and chemotherapy alone were analyzed. The prognostic factors affecting the survival of patients were analyzed by univarite analysis and multivariate analysis.
Results: There were 119 male（59.5％） and 81 female（40.5%） in 200 cases B-CLPD patients， the sex ratio(male/female) was 1.5∶1 with median age of 61（30- 91） years old. The distribution of subtypes were as fallows: 51 cases (25.5%) of chronic lymphocytic leukemia/small lymphocytic lymphoma（CLL/SLL）， 64（32.0%） cases of follicular lymphoma（FL）， 40（20.0%） cases mantle cell lymphoma（MCL）， 30（15.0%） cases of marginal zone lymphoma（MZL）， 10（5%） cases of lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia（LPL/WM）， 5（2.5%） cases of B cell chronic lymphoproliferative disorders unclassified（B-CLPD-U） . The main clinical manifestation of 102 patients was lymph node enlargement, 32 cases were complicated with B symptoms. Among CLL/SLL patients， there were 12（23.5%） cases in Binet A and 39（76.5%） cases in Binet B/C. There were 29 patients（20.9%） in Ann Arbor or Lugano stage I-II and 110 cases（79.1%） in stage III-IV of other subtypes. The complete remission（CR） rate was 43.1%（25/58）， 40.2%（39/97）， 7.1%（1/14）， and overaIl response rate（ORR） was 87.9%（51/58）， 62.9%（61/97）， 28.6%（4/14） in the groups of BTK inhibitors， rituximab-based therapy， and chemotherapy alone. The 3-year OS rate and PFS rate in all patients was 79.2% and 72.4% respectively. The 3-year OS rate of patient with MZL, CLL/SLL, FL,WM was 94.7%, 87.7%, 86.8% and 83.3% respectively, while the 3-year OS rate of MCL was only 40.6%, which was significantly lower than other subtypes. The median OS of patients treated with BTK inhibitors and rituximab-based therapy was 20.5 and 18.5 months respectively， and the 3-year OS rate was 97.4% and 90.7%. However， the median PFS of patients receiving chemotherapy alone was 4 months， and the 1-year OS rate was 52.7%， which was statistically significant compared with the other two groups（P<0.05）. Univarite analysis showed that anemia， elevated lactate dehydrogenase， elevated β2-microglobulin， and splenomegaly were the poor prognostic factors for OS（P<0.05）， elevated lactate dehydrogenase was also poor prognostic factors for PFS（P<0.05）. Multifactor analysis showed that anemia and elevated lactate dehydrogenase were the independent poor prognostic factors for survival（P<0.05）.
Conclusion: The clinical features of B-CLPD was various， anemia and elevated lactate dehydrogenase are the prognostic factors for poor survival. BTK inhibitors and new immunotherapy can improve the survival and prognosis of patients in the new drug era.
题目: 新药时代200例B细胞慢性淋巴增殖性疾病患者的临床特征及预后.
目的: 探讨新药治疗时代B细胞慢性淋巴增殖性疾病（B-CLPD）患者初诊时的临床特征及新药治疗对疗效和生存的影响.
方法: 回顾性分析2015年4月至2021年8月间就诊的200例B-CLPD患者的临床和实验室特征，分析在含布鲁顿酪氨酸激酶（BTK）抑制剂、以利妥昔单抗为基础的免疫治疗及单纯化疗等不同治疗方案下患者的临床疗效和生存情况。并行单因素分析和多因素分析影响患者生存的预后因素.
结果: 200例患者中男性119例（59.5％），女性81例（40.5%），男女比例约1.5∶1，中位确诊年龄61（30-91）岁。200例患者亚型分布为CLL/SLL 51例（25.5%），FL 64例（32.0%），MCL 40例（20.0%），MZL 30例（15.0%），LPL/WM 10例（5%），B-CLPD-U 5例（2.5%）。102例（51.0%）患者以淋巴结肿大为主要临床表现，32例（16.0%）患者合并有B症状。CLL/SLL患者中Binet A期12例（23.5%）、Binet B/C期39例（76.5%），其他亚型患者Ann Arbor或Lugano分期I-II期29例（20.9%），Ⅲ-Ⅳ期110例（79.1%）。58例接受含BTK抑制剂治疗的患者有43.1%（25/58）获得CR，ORR为87.9%（51/58），97例以利妥昔单抗为基础治疗的患者有40.2%（39/97）获得CR，ORR为62.9%（61/97），14例接受单纯化疗的患者仅7.1%（1/14）获得CR，ORR为28.6%（4/14）。所有患者3年OS率和PFS率分别为79.2%和72.4%。MZL、CLL/SLL、FL、WM患者的3年OS率分别为94.7%、87.7%、86.8%和83.3%，而MCL患者的3年OS率仅为40.6%，明显低于上述其他亚型（P<0.05）。含BTK抑制剂治疗的患者中位OS为20.5个月，3年OS率为97.4%，以利妥昔单抗为基础治疗的患者中位OS为18.5个月，3年OS率为90.7%；单纯化疗的患者中位PFS为4个月，1年OS率为52.7%，单纯化疗组的PFS、OS与前两组比较差异有统计学意义（P<0.05）。单因素分析结果显示，合并贫血、乳酸脱氢酶升高、β2-微球蛋白升高、存在脾脏肿大对OS有显著影响（P<0.05），乳酸脱氢酶升高对PFS有显著影响（P<0.05）；多因素分析结果显示，合并贫血（P<0.05）和乳酸脱氢酶升高（P<0.05）是患者生存的独立预后不良因素.
结论: B-CLPD是一类临床异质性较大的疾病，合并贫血和乳酸脱氢酶升高是评估患者生存不良的预后因素，新药时代BTK抑制剂和新型免疫治疗可以改善患者的生存和预后.
Keywords: B cell chronic lymphoproliferative disorders; BTK inhibitor; clinical features; prognosis.