克拉屈滨联合白消安和阿糖胞苷预用药在异基因造血干细胞移植治疗急性髓系白血病中的作用

Clinical efficacy of conditioning regimen using clarithromycin in combination with busulfan and cytarabine in patients with acute myeloid leukemia before allogeneic hematopoietic stem cell transplantation

目的探讨在异基因造血干细胞移植(allo-HSCT)治疗急性髓系白血病(AML)手术患者予以克拉屈滨、白消安、阿糖胞苷联合用药预处理的临床疗效及其安全性。方法回顾性分析2016年8月至2024年2月在空军军医大学第二附属医院予以allo-HSCT治疗的79例AML患者的资料,随访至2024年5月30日,所有患者移植前接受克拉屈滨、白消安、阿糖胞苷3药预处理方案。分析植入情况、急/慢性移植物抗宿主病(a/cGVHD)的发生率、感染发生、复发率、预处理相关毒性反应、总生存期(OS)、无进展生存期(PFS)及影响预后的危险因素。结果79例AML患者粒系植入的时间为13(7,20)d,血小板植入时间为14(8,22)d;10例发生急性GVHD,15例发生慢性GVHD,64例供体为单倍体患者中出现22例GVHD,发生率为34.38%,15例供体为全合患者中出现3例GVHD,发生率为20.00%。移植后100 d内,3例患者因感染死亡,1例患者因脑出血死亡,1年累积复发率和移植相关死亡率分别为16.45%和5.06%,1年的预期OS及PFS分别为80.7%和77.5%。多因素回归可以观察到移植后维持治疗、移植前微小残留病灶(MRD)阴性是影响患者生存的危险因素(均P<0.05)。结论对于有allo-HSCT指征的AML患者,采用克拉屈滨、白消安、阿糖胞苷三药预处理方案可减轻预处理相关毒性,安全性良好,结合移植后维持治疗,移植复发率较低。

Objective To explore the clinical efficacy and safety of a three drug conditioning regimen consisting of busufan,cladribin and cytarabine in allogeneic hematopoietic stem cell transplantation(allo-HSCT)for treating acute myeloid leukemia(AML).Methods A retrospective analysis was conducted on clinical data of 79 AML patients undergoing allo HSCT from August 2016 to February 2024 in the Second Affiliated Hospital of Air Force Military Medical University.All patients received the conditioning regimen using cladribin in combination with busulfan and cytarabine before transplantation.The implantation status,incidence of acute/chronic graft-versus-host disease(a/cGVHD),infection incidence,recurrence rate,conditioning-related toxic reactions,overall survival(OS),progression free survival(PFS)and risk factors affecting prognosis were analyzed.Results The time of granulograft implantation in the 79 AML patients was 13(7,20)days,and the median time of platelet implantation was 14(8,22)days.Acute GVHD occurred in 10 patients,chronic GVHD occurred in 15 patients,and GVHD occurred in 22 of 64 patients with haploid donors,with an incidence of 34.38%.GVHD occurred in 3 of 15 patients with total donors,with an incidence of 20.00%.Within 100 days after transplantation,3 patients died due to infection and 1 patient died due to cerebral hemorrhage.The 1-year cumulative recurrence rate and transplant-related mortality were 16.45%and 5.06%,respectively.The 1-year expected OS and PFS were 80.7%and 77.5%,respectively.Multivariate regression showed that maintenance therapy after transplantation and negative minimal residual disease(MRD)before transplantation were risk factors for survival(both P<0.05).Conclusion For AML patients with allo-HSCT indications,a three-drug conditioning regimen using cladobine in combination with alsulafil and cytarabine can be adopted to reduce pretreatment-related toxicity and it is of good safety.This regimen plus post-transplantation maintenance therapy can result in low transplantation recurrence rate.