克拉屈滨、吉西他滨、阿糖胞苷和白消安联合预处理方案在恶性淋巴瘤自体造血干细胞移植治疗中的疗效和安全性

Efficacy and safety of combined pretreatment regimen of cladribine,gemcitabine,cytosine arabinoside and busulfan in autologous hematopoietic stem cell transplantation for malignant lymphoma

目的探讨克拉屈滨、吉西他滨、阿糖胞苷、白消安(CLGAB)联合预处理方案在恶性淋巴瘤自体造血干细胞移植(ASCT)中的疗效和安全性。方法采用前瞻性、同期临床对照试验,选择2020年1月至2021年12月于河南省人民医院血液科行ASCT的34例恶性淋巴瘤患者为研究对象,根据预处理方案将患者分为对照组(n=19)和观察组(n=15)。对照组患者采用卡莫司汀/苯达莫司汀/司莫司汀、依托泊苷、阿糖胞苷、美法仑联合方案预处理,观察组患者采用CLGAB方案预处理。比较2种预处理方案对肿瘤细胞的杀伤作用、不良反应、造血重建效果、移植后疾病缓解及患者生存情况等。结果2组采集到的单个核细胞值比较差异无统计学意义(t=0.977,P>0.05)。2组采集到的CD34+细胞水平比较差异无统计学意义(P>0.05)。2组患者预处理后均达到Ⅳ度骨髓抑制,观察组患者预处理后达Ⅳ度骨髓抑制时间显著短于对照组(P<0.05)。观察组患者中性粒细胞和血小板(PLT)植入时间显著早于对照组(P<0.05);观察组患者移植期间应用血小板生成素时间显著短于对照组(P<0.05)。2组患者的PLT最低值、粒细胞缺少持续时间、应用粒细胞集落刺激因子时间、输注PLT数量及输注红细胞数量比较差异无统计学意义(P>0.05)。2组患者恶心/呕吐、发热、腹泻、口腔黏膜炎、肝损伤、低血钾、出血及心脏毒性不良反应发生率比较差异无统计学意义(P>0.05);2组患者的Ⅲ/Ⅳ级严重不良反应发生率较低,均未发生肝静脉闭塞性疾病及移植相关死亡。移植后3个月,观察组患者获得完全缓解(CR)15例(100.0%),早期总反应率(ORR)为100.0%(15/15);对照组患者获得CR 15例(78.9%),部分缓解1例(5.3%),疾病稳定1例(5.3%),疾病进展2例(10.5%),早期ORR为84.2%(16/19);2组患者早期ORR比较差异无统计学意义(P>0.05)。观察组无复发和死亡病例,患者的PFS率和OS率均为100.0%。对照组3例患者复发,1例因疾病进展死亡,患者的PFS率和OS率分别为84.2%、94.7%。2组患者的PFS率、OS率比较差异无统计学意义(P>0.05)。结论CLGAB预处理方案杀伤肿瘤细胞效果理想且预处理毒性可耐受,造血重建较快,早期疗效好,复发率低,是恶性淋巴瘤ASCT可行、有效的预处理方案。

Objective To investigate the efficacy and safety of the combined pretreatment regimen of cladribine,gemcitabine,cytosine arabinoside and busulfan(CLGAB)in autologous hematopoietic stem cell transplantation(ASCT)for malignant lymphoma.Methods A prospective,concurrent clinical controlled trial was conducted,a total of 34 malignant lymphoma patients who underwent ASCT in the Department of Hematology,Henan Provincial People′s Hospital from January 2020 to December 2021 were selected as the study subjects,and the patients were divided into control group(n=19)and observation group(n=15)according to the pretreatment regimen.The patients in the control group were pretreated with the regimen of carmustine/bendamostine/simustine,etoposide,cytosine arabinoside,and mephalon,the patients in the observation group were pretreated with the regimen of CLGAB.The killing effect on tumor cells,adverse reaction of pretreatment,hematopoiesis reconstruction,disease remission and survival of patients between the two regimens were compared.Results There was no significant difference in mononuclear cell values of patients between the two groups(t=0.977,P>0.05).There was no significant difference in CD34+cells level of patients between the two groups(P>0.05).The patients in both groups all reachedⅣdegree of bone marrow suppression after pretreatment,and the time of reachingⅣdegree of bone marrow suppression after pretreatment of patients in the observation group was significantly shorter than that in the control group(P<0.05).The implantation time of neutrophils and platelets(PLT)of patients in the observation group were significantly earlier than those in the control group(P<0.05).The time of thrombopoietin application during transplantation of patients in the observation group was significantly less than that in the control group(P<0.05).There was no significant difference in the minimum value of PLT,duration of granulocyte deficiency,time of granulocyte colony-stimulating factor application,number of PLT transfusions and number of red blood cells transfused for patients between the two groups(P>0.05).There was no significant difference in the incidences of nausea/vomiting,fever,diarrhea,oral mucositis,liver injury,hypokalemia,bleeding and adverse cardiac reactions of patients between the two groups(P>0.05);the incidences of ClassⅢ/Ⅳserious adverse reactions of patients in the two groups were low,and there was no hepatic vein occlusive disease and transplantation related mortality.Three months after transplantation,complete remission(CR)was obtained in 15 patients(100.0%),and the early overall response rate(ORR)was 100.0%(15/15)in the observation group;in the control group,CR was obtained in 15 cases(78.9%),partial remission in 1 case(5.3%),stable disease in 1 case(5.3%),progressive disease in 2 cases(10.5%),and the early ORR was 84.2%(16/19);there was no significant difference in early ORR of patients between the two groups(P>0.05).There was no recurrence or death in the observation group,and the progress free survival(PFS)rate and overall survival(OS)rate of patients were both 100.0%.In the control group,3 patients relapsed and 1 patient died due to disease progression,the PFS rate and OS rate of patients were 84.2%and 94.7%respectively.There was no significant difference in the PFS rate and OS rate of patients between the two groups(P>0.05).Conclusion CLGAB regimen has ideal myeloablative effect,tolerable pretreatment toxicity,rapid hematopoietic reconstruction,good early efficacy and low recurrence rate,it is a feasible and effective pretreatment regimen for ASCT of lymphoma.