成人急性髓系白血病患者微移植治疗后的临床疗效及生存分析

Clinical Efficacy and Survival Analysis of Adult Patients with Acute Myeloid Leukemia after Microtransplantation

目的:探究微移植(MST)治疗成人急性髓系白血病(AML)患者的疗效及生存影响因素。方法:回顾性分析单中心2014年7月至2021年10月接受MST治疗的AML患者27例,中位年龄59(29-77)岁,年龄≥60岁者13例,<60岁者14例,男13例,女14例。疾病按FAB分型:AML-M26例,AML-M46例,AML-M52例,AML-M62例,AML(未分型)9例,AML髓系肉瘤2例(原发AML 21例,MDS继发AML 6例)。细胞遗传学分析示正常核型患者25例,异常核型患者2例,分子生物学异常患者20例。诱导化疗方案主要包括:IA、DA、MA或HA方案,个别使用CAG或CIG联合地西他滨,以及单药地西他滨等方案。诱导化疗1个疗程获完全缓解(CR)的患者17例,2个疗程获得CR的患者4例。地西他滨4个疗程获得CR患者3例,未获缓解的2例,1例患者未行诱导化疗,直接行MST治疗。移植前达CR的患者16例,移植前未缓解的患者11例。随访主要采用查阅患者病历资料以及电话问询,观察MST治疗的不良反应与疗效。通过Kaplan-Meier进行生存分析,主要观察指标总生存期(OS)和无白血病生存(LFS),并进行Log-rank检验。通过Cox回归模型进行多因素分析。结果:27例AML患者共进行79例次MST,总体安全性良好,无特殊严重不良反应发生。患者白细胞恢复中位时间13(4-28)天,血小板恢复中位时间13(4-30)天。发生感染50例次,肝功能异常5例次,心功能异常3例次,除了心功能异常外,其它并发症未影响治疗均治愈。所有患者在治疗期间及随访期间均未观察到急性或慢性移植物抗宿主病(GVHD)、肾功能不全、凝血功能异常及严重出血。截至随访日期,中位随访时间79(14-171)个月,中位OS时间为62(1-171)个月,中位LFS时间为15(0-171)个月。2年OS率为65.7%(17/27),2年LFS率为47.4%(12/27)。27例患者MST治疗后完全缓解率为48.1%(13/27)。8例患者在接受MST治疗过程中复发,其中7例第1次MST疗程完成后复发,1例第2次MST疗程完成后复发。2例患者在MST疗程结束后复发。13例患者死亡,其中10例患者死于疾病进展,2例患者死于严重感染,1例患者死于心脏损害。结论:MST具有药物毒副作用小、不需要HLA配型完全相合、有效避免GVHD、造血恢复快等优势,可改善老年AML和部分年轻AML患者的OS及LFS,是无HLA相合配型患者的治疗选择之一。

Objective:To investigate the clinical efficacy and survival factors of microtransplantation(MST)in adult patients with acute myeloid leukemia(AML). Methods:For a retrospective analysis of27adult patients with AML receiving MST from July2014to October2021,the median age was59(29-77)years old, 13cases were≥60years old, 14case were< 60years old, 13cases were male and14cases were female. Classification by FAB:AML-M2 6cases,AML-M4 6cases,AML-M5 2cases,AML-M6 2cases,AML(Undivided type) 9cases,AML myeloid sarcoma2cases(primary AML21cases,AML secondary to MDS6cases). Cytogenetic analysis showed25patients with a normal karyotype, 2patients with an abnormal karyotype,and20patients with an abnormal molecular biology.Induction chemotherapy regimens mainly include:IA,DA,MA or HA regimen,including CAG or CIG in combination with decitabine,and single-agent decitabine.17patients achieved complete remission(CR)after1course of induction chemotherapy and4patients achieved CR after2courses of induction chemotherapy.3patients received CR by four courses of decitabine, 2patients received no remission,and1patient underwent no induction chemotherapy and were treated direct MST. There were16patients with pretransplant CR and11patients were not in remission before transplantation. Follow-up mainly used consult patient′s medical records and telephone inquiry to observe the adverse effects and efficacy of MST treatment. Survival analysis was performed by Kaplan-Meier method,with the main observation indicators overall survival(OS)and leukemia-free survival(LFS),and performed with the Log-rank test.Multivariate analysis was performed by the Cox regression model. Results:A total of79MST were performed in27AML patients with good overall safety and no special serious adverse effects. The median time of leukocyte recovery was13(4-28)days,and the median time of platelet recovery was13(4-30)days. There were50cases of infection, 5cases of abnormal liver function and3cases of abnormal cardiac function. Except for abnormal cardiac function,all other complications did not affect the treatment and were cure. Acute or chronic GVHD,renal insufficiency,abnormal coagulation function,and severe bleeding were not observed during treatment or during follow-up. As of the follow-up date,the median follow-up time of the27patients was79(14-171)months,the median OS time was62(1-171)months,and the median LFS time was15(0-171)months. The2-year OS rate was65.7%(17/27),and the2-year LFS rate was47.4%(12/27). The complete response rate of27patients treated with MST was48.1%(13/27).8patients relapsed during MST treatment,including7patients after the completion of the first MST course and1patient after the completion of the second MST course.2patients relapsed after the end of the course of MST.13patients died,including10patients because of disease progression,two patients from severe infection,and one patient from cardiac damage. Conclusion:MST has the advantages of small toxic side effects,complete compatibility of HLA matching is not required,effective avoidance of GVHD and rapid hematopoietic recovery,which can improve OS and LFS in elderly AML and young AML patients,and is one of the treatment options for patients without HLA matching.