地西他滨联合异基因造血干细胞移植治疗慢性粒-单核细胞白血病的临床研究

Clinical study of decitabine combined with allogeneic hematopoietic stem cell transplantation in the treatment of chronic myelomonocytic leukemia

目的:对临床上使用地西他滨联合异基因造血干细胞移植治疗慢性粒-单核细胞白血病(CMML)患者进行回顾性研究。方法:对2014—2020年在苏州大学附属第一医院血液科接受地西他滨治疗并进行异基因造血干细胞移植的18例CMML患者进行回顾性分析,评价其总生存率,无白血病生存率,累积复发率及治疗相关死亡率等指标,观察18例患者植入、移植物抗宿主病(GVHD)、复发及生存情况。同时根据患者预处理方案中是否桥接地西他滨,将患者分为地西他滨桥接改良BU/CY预处理组和其他预处理方案组,比较以上指标。结果:(1)纳入18例CMML患者(男13例,女5例),中位年龄31(13~52)岁;10例患者仅在移植前病程中接受地西他滨治疗,采用改良BU/CY及其他预处理方案,8例患者采用地西他滨桥接改良BU/CY预处理方案;其中无关全相合移植1例,亲缘全相合移植5例,亲缘单倍体移植12例。(2)18例患者均获得供者型植入,粒系植入中位时间14(11~21)d,巨核系中位植入时间20(9~40)d,2组预处理方案间粒系植入时间、巨核系植入时间差异无统计学意义。(3)13例患者发生急性GVHD,总发生率为72.2%(95%CI 49.3~95.1);Ⅲ~Ⅳ度急性GVHD 7例,发生率为38.9%(95%CI 13.9~63.8);2组预处理方案间急性GVHD的发生率差异无统计学意义(P>0.05)。(4)18例患者中共有9例死亡,3例为复发相关死亡,3年累积复发率为17.3%±0.9%,中位复发时间157(104~406)d;6例为移植相关死亡,3年移植相关死亡率为33.3%±1.3%。(5)3年总生存率为55.6%±11.7%,3年无白血病生存率为49.4%±11.9%,2组预处理方案间总生存率和无白血病生存率差异无统计学意义(P>0.05)。结论:含地西他滨的预处理方案桥接异基因造血干细胞移植治疗CMML是安全可行的。

Objective: To explore the therapeutic effect of demethylation drugs application prior to allogeneic hematopoietic stem cell transplantation(allo-HSCT) in patients with chronic myelomonocytic leukemia(CMML). Methods: Clinical data of 18 CMML patients treated with demethylation drugs prior to allo-HSCT in the Department of Hematology at the First Affiliated Hospital of Soochow University from 2014 to 2020 were retrospectively analyzed. We evaluated the overall survival rate(OS), leukemia-free survival rate(LFS), cumulative relapse rate, treatment-related mortality and graft versus host disease(GVHD). Results:(1)18 CMML patients(13 males and 5 females) were enrolled, with a median age of 31(13-52) years old. Eight cases treated with decitabine bridging BU/CY conditioning regimen, 10 cases treated with BU/CY and other conditioning regimen, including 1 case of irrelevant homologous transplantation, 5 cases of related homologous transplantation, and 12 cases of related haploid transplantation.(2)18 patients all received donor type implantation. The median implantation time of granule implantation was 14(11-21) days, and the median implantation time of megakaryocyte was 20(9-40) days. There was no significant difference between two kinds of conditioning regimens.(3)13 patients developed acute GVHD, with a total incidence of 72.2%(95%CI 49.3 to 95.1);7 cases developed grade Ⅲ-Ⅳacute GVHD, with an incidence of 38.9%(95%CI 13.9 to 63.8). There was no statistical difference in the incidence of acute GVHD between the two conditioning regimens(P>0.05).(4)There were 9 deaths in 18 patients, 3 cases of them were relapse-related deaths, the 3-year cumulative relapse rate was 17.3%±0.9%, and the median relapse time was 157(104-406) days;6 cases were transplant-related deaths, 3 years of transplantation related mortality rate was 33.3%±1.3%.(5)The 3-year OS rate was 55.6%±11.7%, and the 3-year LFS rate was 49.4%±11.9%. There was no significant difference in OS and LFS between the two conditioning regimens(P>0.05). Conclusion: Treating CMML patients with decitabine combined with allo-HSCT is feasible.