不同化疗方案治疗弥漫大B细胞淋巴瘤患者的疗效及不良反应分析

Analysis of efficacy and adverse reactions of different chemotherapy regimens in treatment of patients with diffuse large B-cell lymphoma

目的探讨不同化疗方案治疗弥漫大B细胞淋巴瘤(DLBCL)患者的疗效及不良反应。方法选择2013年1月1日至2018年12月31日,于贵州医科大学附属医院诊治的130例年龄≥16岁的DLBCL患者为研究对象。患者的中位年龄为52岁(17~80岁);男性患者为73例,女性为57例。根据130例DLBCL患者接受的治疗方案不同,将其分为:利妥昔单抗组(n=107)和非利妥昔单抗组(n=23)、依托泊苷组(n=39)和非依托泊苷组(n=91)、脂质体多柔比星组(n=29)和非脂质体多柔比星组(n=101)。采用回顾性队列研究的方法,收集患者的性别、年龄、国际预后指数(IPI)评分,临床分期等临床病例资料,以及不良反应发生情况,并且比较不同治疗方案对患者近期疗效、远期预后及安全性的影响。对患者的随访截至2019年12月31日。患者的性别、年龄、IPI评分、临床分期构成比等计数资料的组间比较,采用χ^(2)检验或连续性校正χ^(2)检验。生存分析采用Kaplan-Meier法,组间总体生存(OS)、无进展生存(PFS)率的比较,采用log-rank检验。本研究遵循的程序符合2013年修订版《世界医学协会赫尔辛基宣言》要求。结果①本研究中,利妥昔单抗组与非利妥昔单抗组、依托泊苷组与非依托泊苷组、脂质体多柔比星组与非脂质体多柔比星组患者的一般临床资料分别比较,差异均无统计学意义(P>0.05)。②利妥昔单抗组患者的3年PFS和OS率分别为78.2%和82.6%,均高于非利妥昔单抗组患者的46.1%和63.2%,并且差异均有统计学意义(χ^(2)=5.442、3.895,P=0.020、0.048)。但是2组患者的完全缓解(CR)率[61.7%(66/107)比47.8%(11/23)]、总体反应率(ORR)[83.2%(89/107)比87.0%(20/23)]、不良反应发生率[74.8%(80/107)比78.3%(18/23)]分别比较,差异均无统计学意义(χ^(2)=1.458、0.457、0.125,P=0.227、0.499、0.724)。③依托泊苷组和非依托泊苷组患者的CR率[51.3%(20/39)比62.6%(57/91)]、ORR[87.2%(34/39)比82.4%(75/91)]、3年PFS(63.6%比73.0%)、3年OS率(75.1%比80.8%)、不良反应发生率[84.6%(33/39)比71.4%(65/91)]分别比较,差异均无统计学意义(χ^(2)=1.458、0.457、<0.001、0.314、2.558,P=0.227、0.499、0.994、0.575、0.110)。但是依托泊苷组患者的血液学不良反应[76.9%(30/39)比57.1%(52/91)]、Ⅲ~Ⅳ级血液学不良反应[59.0%(23/39)比38.5%(35/91)]及肝功能损害的发生率[46.2%(18/39)比16.5%(15/91)],均高于非依托泊苷组,并且差异均有统计学意义(χ^(2)=4.586、4.649、12.668,P=0.032、0.031、<0.001)。④脂质体多柔比星组与非脂质体多柔比星组患者的CR率[58.6%(17/29)比59.4%(60/101)]、ORR[79.3%(23/29)比85.1%(86/101)]、3年PFS率(78.1%比76.0%)、3年OS率(85.2%比78.7%)分别比较,差异均无统计学意义(χ^(2)=0.006、1.382、0.770、0.868,P=0.940、0.265、0.380、0.352)。但是脂质体多柔比星组患者的不良反应[58.6%(17/29)比80.2%(81/101)]、血液学不良反应[44.8%(13/29)比68.3%(69/101)]、Ⅲ~Ⅳ级血液学不良反应的发生率[27.6%(8/29)比49.5%(50/101)],分别均低于非脂质体多柔比星组,并且差异均有统计学意义(χ^(2)=5.653、5.338、4.381,P=0.017、0.021、0.036)。结论DLBCL化疗方案中,利妥昔单抗的使用可提高患者的PFS和OS率;依托泊苷的使用并未提高疗效,反而使不良反应发生率增加;脂质体多柔比星的使用可显著降低不良反应发生率,特别是减少Ⅲ~Ⅳ级血液学不良反应的发生。

Objective To explore efficacy and adverse reactions of different chemotherapy regimens in treatment of patients with diffuse large B-cell lymphoma(DLBCL).Methods From January 1,2013 to December 31,2018,a total of 130 DLBCL patients over 16 years old who were diagnosed and treated in Affiliated Hospital of Guizhou Medical University were selected as research subjects.The median age of them was 52 years(17-80 years).There were 73 male and 57 female patients.All 130 patients were classified into different groups according to chemotherapy regimens:rituximab group(n=107)and non-rituximab group(n=23),etoposide group(n=39)and non-etoposide group(n=91),as well as liposomal doxorubicin group(n=29)and non-liposomal doxorubicin group(n=101).Using retrospective cohort study method,patients′gender,age,international prognostic index(IPI)score,clinical stage,adverse reactions and other clinical data were collected,and short-term efficacy,long-term prognosis and safety of different regimens groups were compared.This study was followed up until December 31,2019.The comparison ratios of gender,age,IPI score,clinical stage and other clinical data of patients between two different groups were performed by chi-square test or correction for continuity.The Kaplan-Meier method was used for survival analysis,and overall survival(OS)and progression-free survival(PFS)rates between different groups were compared by log-rank test.This study was in line with World Medical Association Declaration of Helsinki revised in 2013.Results①In this study,the general clinical data of patients between rituximab group and non-rituximab group,etoposide group and non-etoposide group,liposomal doxorubicin group and non-liposomal doxorubicin group were compared,and the differences were not statistically significant(P>0.05).②The 3-year PFS and OS rates of patients in rituximab group were 78.2%and 82.6%respectively,which were higher than those of 46.1%and 63.2%in non-rituximab group,and the differences were statistically significant(χ^(2)=5.442,3.895;P=0.020,0.048).However,the complete remission(CR)rates[61.7%(66/107)vs 47.8%(11/23)],overall response rate(ORR)[83.2%(89/107)vs 87.0%(20/23)],and incidences of adverse reactions[74.8%(80/107)vs 78.3%(18/23)]between two groups were not statistically significant[χ^(2)=1.458,0.457,0.125;P=0.227,0.499,0.724].③There were no significant differences in CR rates[51.3%(20/39)vs 62.6%(57/91)],ORR[87.2%(34/39)vs 82.4%(75/91)],3-year PFS rates(63.6%vs 73.0%),3-year OS rates(75.1%vs 80.8%)and incidences of adverse reaction[84.6%(33/39)vs 71.4%(65/91)]of patients between etoposide group and non-etoposide group(χ^(2)=1.458,0.457,<0.001,0.314,2.558;P=0.227,0.499,0.994,0.575,0.110).However,the incidences of hematological adverse reactions[76.9%(30/39)vs 57.1%(52/91)],gradeⅢtoⅣhematological adverse reactions[59.0%(23/39)vs 38.5%(35/91)]and liver dysfunction[46.2%(18/39)vs 16.5%(15/91)]of patients in etoposide group,were all higher than those of non-etoposide group,and the differences were statistically significant(χ^(2)=4.586,4.649,12.668;P=0.032,0.031,<0.001).④The CR rates[58.6%(17/29)vs 59.4%(60/101)],ORR[79.3%(23/29)vs 85.1%(86/101)],3-year PFS rates(78.1%vs 76.0%)and 3-year OS rates(85.2%vs 78.7%)of patients between liposomal doxorubicin group and non-liposomal doxorubicin group were compared,and the differences were not statistically significant(χ^(2)=0.006,1.382,0.770,0.868;P=0.940,0.265,0.380,0.352).However,the incidences of adverse reactions[58.6%(17/29)vs 80.2%(81/101)],hematological adverse reactions[44.8%(13/29)vs 68.3%(69/101)],and gradeⅢ-Ⅳhematological adverse reactions[27.6%(8/29)vs 49.5%(50/101)]of patients in liposomal doxorubicin group were lower than those of non-liposomal doxorubicin group,and the differences were statistically significant(χ^(2)=5.653,5.338,4.381;P=0.017,0.021,0.036).Conclusions In chemotherapy regimens for treatment of DLBCL patients in this study,the use of rituximab could improve PFS and OS rates of patients.Adding etoposide in chemotherapy regimens could not improve efficacy,but it increases incidences of adverse reactions.And the use of liposomal doxorubicin-based chemotherapy could significantly reduce incidences of adverse reactions,especially decrease incidences of gradeⅢ-Ⅳhematological adverse reactions.