BeEAM/C预处理方案在自体造血干细胞移植治疗外周T细胞淋巴瘤患者中的疗效与安全性

Efficacy and safety of BeEAM/C pretreatment regimen in autologous hematopoietic stem cell transplantation for patients with peripheral T-cell lymphoma

目的探讨BeEAM/C(苯达莫司汀+依托泊苷+阿糖胞苷+美法仑/环磷酰胺)预处理方案在自体造血干细胞移植(atuo-HSCT)治疗外周T细胞淋巴瘤(PTCL)患者中的疗效与安全性。方法选择2021年7月至2023年1月天津医科大学肿瘤医院淋巴瘤内科收治并进行BeEAM/C方案预处理auto-HSCT的30例PTCL患者为研究对象,纳入BeEAM/C组。选择2018年7月至2021年6月于本院接受GBM/C(吉西他滨+白消安+美法仑/环磷酰胺)方案预处理auto-HSCT的30例PTCL患者作为历史对照,纳入GBM/C组。BeEAM/C组与GBM/C组患者年龄分别为(43.2±10.3)岁和(38.6±11.8)岁;男性患者分别为19和17例,女性患者分别为11和13例。采用回顾性研究方法,收集2组患者相关临床资料,比较2组患者的造血重建、预后及不良反应发生情况,对2组患者的随访截至2023年4月30日。2组患者年龄、性别构成比等一般临床资料分别比较,差异均无统计学意义(均P>0.05)。根据本研究定量资料的分布,2组比较采用Mann-Whitney U检验或成组t检验;定性资料比较采用χ^(2)检验。采用Kaplan-Meier法绘制2组患者的总体生存(OS)和无进展生存(PFS)曲线,2组比较采用log-rank法。本研究遵循的程序符合天津医科大学肿瘤医院人体试验委员会制定的标准,经过该伦理委员会批准(批准文号:2018LH-KS-025),并与所有受试者签署临床研究知情同意书。结果①本研究BeEAM/C组和GBM/C组患者的骨髓受累、病理分型、疾病分期、既往治疗线数、移植前疗效、国际预后指数(IPI)评分构成比分别比较,差异均无统计学意义(均P>0.05)。②BeEAM/C组和GBM/C组患者回输的单核细胞(MNC)中位数(4.80×10^(8)/kg比5.23×10^(8)/kg)、CD34^(+)细胞中位数(2.09×10^(6)/kg比1.85×10^(6)/kg)、中性粒细胞植入中位时间(13 d比12 d)、血小板植入中位时间(15 d比15 d)分别比较,差异均无统计学意义(U=379.00、P=0.294,U=394.50、P=0.412,U=388.00、P=0.353,U=-439.50、P=0.876)。③截至2023年4月30日,对BeEAM/C组患者中位随访时间为12.5个月(10.3,16.0个月),随访期间4例患者疾病进展(PD),1例死亡;对GBM/C组的中位随访时间为31.5个月(20.8,35.0个月),随访期间8例患者PD,2例死亡。BeEAM/C组和GBM/C组患者的1年PFS率分别为84.3%和90.0%,1年OS率分别为96.6%和93.2%,2组分别比较,差异均无统计学意义(χ^(2)=0.29、P=0.589,χ^(2)=0.20、P=0.656)。④BeEAM/C组和GBM/C组患者的Ⅳ级中性粒细胞减少及血小板减少发生率均为100.0%(30/30);2组患者Ⅲ~Ⅳ级贫血发生率比较,差异无统计学意义[56.7%(17/30)比63.3%(19/30),χ^(2)=0.28,P=0.598]。GBM/C组患者黏膜炎、胃肠道不良反应发生率,均高于BeEAM/C组,并且差异均有统计学意义[73.3%(22/30)比46.6%(14/30),χ^(2)=4.44,P=0.035;93.4%(28/30)比70.0%(21/30),χ^(2)=5.46,P=0.020]。结论对于接受auto-HSCT的PTCL患者,采取BeEAM/C预处理方案与GBM/C预处理方案的短期预后疗效相当,但前者所致黏膜炎及胃肠道不良反应风险下降,安全性相对更高。

Objective To explore the efficacy and safety of BeEAM/C(bendamustine+etoposide+cytarabine+melphalan/cyclophosphamide)regimen pretreatment in patients with peripheral T-cell lymphoma(PTCL)treated with autologous hematopoietic stem cell transplantation(atuo-HSCT).Methods From July 2021 to January 2023,a total of 30 PTCL patients who underwent auto-HSCT with BeEAM/C regimen pretreatment in Lymphoma Department of Tianjin Medical University Cancer Institute and Hospital were selected as research subjects and included in BeEAM/C group.From July 2018 to June 2021,a total of 30 PTCL patients who underwent auto-HSCT with GBM/C(gemcitabine+busulfan+melphalan/cyclophosphamide)regimen pretreatment were selected as historical controls and included in the GBM/C group.The ages of patients in BeEAM/C group and GBM/C group were(43.2±10.3)years and(38.6±11.8)years.There were 19 and 17 male patients,and 11 and 13 females,respectively.Using a retrospective study method,relevant clinical data were collected and hematopoietic reconstitution,prognosis,and incidence of adverse reactions were compared between two groups of patients.This study was followed up until April 30,2023.There was no statistically significant difference in the general clinical data between the two groups of patients(all P>0.05).According to the distribution of quantitative data in this study,the two groups were compared using Mann Whitney U test or group t-test.Qualitative data comparison were performed by chi-square test.The Kaplan-Meier method was used to plot the overall survival(OS)and progression free survival(PFS)curves of two groups,and compared by log-rank method.The procedures followed in this study were in accordance with the standards established by the Human Trials Committee of Tianjin Medical University Cancer Institute and Hospital,and had been approved by the ethics committee(Approval No.2018LH-KS-025).Clinical study informed consent forms had been signed with all patients.Results①In this study,the component ratios of bone marrow involvement,pathological classification,disease stage,number of previous treatment lines,pre-transplantation outcome,and international prognostic index(IPI)score between BeEAM/C and GBM/C groups were compared,and the differences were not statistically significant(all P>0.05).②The median monocyte count(MNC)(4.80×10^(8)/kg vs 5.23×10^(8)/kg),median CD34^(+)cells(2.09×10^(6)/kg vs 1.85×10^(6)/kg),median time of neutrophil implantation(13 d vs 12 d),and median time of platelet implantation(15 d vs 15 d)of patients between BeEAM/C and GBM/C groups were compared respectively,and the differences were not statistically significant(U=379.00,P=0.294;U=394.50,P=0.412;U=388.00,P=0.353;U=-439.50,P=0.876).③As of April 30,2023,the median follow-up time for BeEAM/C group was 12.5 months(10.3,16.0 months),with 4 patients experiencing disease progression(PD)and 1 death during follow-up period.The median follow-up time for GBM/C group was 31.5 months(20.8,35.0 months),with 8 patients with PD and 2 deaths during the follow-up period.The 1-year PFS rates of patients in BeEAM/C group and GBM/C group were 84.3%and 90.0%,and 1-year OS rates were 96.6%and 93.2%,respectively.And the differences between two groups were not statistically significant(χ^(2)=0.29,P=0.589;χ^(2)=0.20,P=0.656).④In this study,the incidence of gradeⅣneutropenia and thrombocytopenia in both BeEAM/C and GBM/C groups were 100.0%(30/30).There was no statistically significant difference in the incidence of gradeⅢ-Ⅳanemia of patients between BeEAM/C group and GBM/C group[56.7%(17/30)vs 63.3%(19/30),χ^(2)=0.28,P=0.598].The incidence of mucosal inflammation and gastrointestinal adverse reactions of patients in GBM/C group was higher than that in BeEAM/C group,and the differences were statistically significant[73.3%(22/30)vs 46.6%(14/30),χ^(2)=4.44,P=0.035;93.4%(28/30)vs 70.0%(21/30),χ^(2)=5.46,P=0.020].Conclusions For the PTCL patients receiving auto-HSCT,the short-term prognosis of BeEAM/C regimen pretreatment is comparable to that of GBM/C regimen pretreatment,but the former reduces the risk of mucosal inflammation and gastrointestinal adverse reactions,and is relatively safer.