Xu Cheng-Bo, Hu Min, Shen Jian-Zhen, Xu Hua-Qin, Zheng Rui-Ji
Department of Hematology， The People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine， Fuzhou 350004， Fujian Province， China.
Department of Hematology， Union Hospital， Fujian Medical University， Fujian Institute of Hematology， Fuzhou 350001， Fujian Province， China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):722-729. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.016.
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.
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.
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（<0.05）. Univarite analysis showed that anemia， elevated lactate dehydrogenase， elevated β2-microglobulin， and splenomegaly were the poor prognostic factors for OS（<0.05）， elevated lactate dehydrogenase was also poor prognostic factors for PFS（<0.05）. Multifactor analysis showed that anemia and elevated lactate dehydrogenase were the independent poor prognostic factors for survival（<0.05）.
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.
分析新药时代B细胞慢性淋巴细胞增殖性疾病（B-CLPD）患者的临床特征以及新药治疗对疗效和生存的影响。
回顾性分析2015年4月至2021年8月期间确诊的200例B-CLPD患者的临床和实验室数据。分析了不同治疗方法（包括布鲁顿酪氨酸激酶（BTK）抑制剂、利妥昔单抗和单纯化疗）下患者的临床疗效和生存情况。通过单因素分析和多因素分析来分析影响患者生存的预后因素。
200例B-CLPD患者中，男性119例（59.5％），女性81例（40.5%），男女比例为1.5∶1，中位年龄为61（30 - 91）岁。亚型分布如下：慢性淋巴细胞白血病/小淋巴细胞淋巴瘤（CLL/SLL）51例（25.5%），滤泡性淋巴瘤（FL）64例（32.0%），套细胞淋巴瘤（MCL）40例（20.0%），边缘区淋巴瘤（MZL）30例（15.0%），淋巴浆细胞淋巴瘤/华氏巨球蛋白血症（LPL/WM）10例（5%），未分类的B细胞慢性淋巴细胞增殖性疾病（B-CLPD-U）5例（2.5%）。102例患者的主要临床表现为淋巴结肿大，32例合并B症状。在CLL/SLL患者中，Binet A期有12例（23.5%），Binet B/C期有39例（76.5%）。Ann Arbor或Lugano I-II期有29例患者（20.9%），其他亚型的III-IV期有110例（79.1%）。BTK抑制剂组、基于利妥昔单抗的治疗组和单纯化疗组的完全缓解（CR）率分别为43.1%（25/58）、40.2%（39/97）、7.1%（1/14），总体缓解率（ORR）分别为87.9%（51/58）、62.9%（61/97）、28.6%（4/14）。所有患者的3年总生存率（OS）和无进展生存率（PFS）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%，明显低于其他亚型。接受BTK抑制剂和基于利妥昔单抗治疗的患者的中位OS分别为20.5个月和18.5个月，3年OS率分别为97.4%和90.7%。然而，单纯接受化疗的患者的中位PFS为4个月，1年OS率为52.7%，与其他两组相比有统计学意义（<0.05）。单因素分析显示，贫血、乳酸脱氢酶升高、β2-微球蛋白升高和脾肿大是OS的不良预后因素（<0.05），乳酸脱氢酶升高也是PFS的不良预后因素（<0.05）。多因素分析显示，贫血和乳酸脱氢酶升高是生存的独立不良预后因素（<0.05）。
B-CLPD的临床特征多样，贫血和乳酸脱氢酶升高是生存不良的预后因素。BTK抑制剂和新的免疫疗法可改善新药时代患者的生存和预后。
