异基因造血干细胞移植治疗骨髓增生异常综合征伴原始细胞增多282例生存分析及WHO 2022分类不同亚型的生存比较

Analysis of the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome with blastomycosis and survival comparison of different subtypes after the WHO 2022 reclassification

目的评估异基因造血干细胞移植(allo-HSCT)治疗骨髓增生异常综合征伴原始细胞增多(MDS-EB)的疗效和预后影响因素,比较WHO2022分类不同亚型患者的预后。方法纳入2006年10月至2022年12月在中国医学科学院血液病医院接受allo-HSCT的282例MDS-EB患者,按照WHO 2022诊断标准重新分类为骨髓增生异常肿瘤伴原始细胞增多1型/2型(MDS-IB1/IB2)(222例)、MDS伴纤维化(MDS-f)(41例)和伴双等位基因TP53突变的MDS(MDS-biTP53)(19例)三组,对其临床资料进行回顾性分析。结果①282例患者中位年龄46(15~66)岁,男191例,女91例,MDS-EB1118例(42%),MDS-EB2164例(58%)。②282例MDS-EB患者中256例(90.8%)移植后获得造血重建,原发植入功能不良11例(3.9%),继发植入功能不良15例(5.3%)。移植后100 d急性移植物抗宿主病(GVHD)累积发生率为(42.6±3.0)%,Ⅱ~Ⅳ度急性GVHD累积发生率为(33.0±2.8)%;移植后1年慢性GVHD累积发生率为(31.0±2.9)%。移植后128例(45.4%)患者发生巨细胞病毒(CMV)感染,63例(22.3%)患者发生菌血症,35例(12.4%)患者发生肺部真菌感染,17例(6.0%)患者发生EB病毒感染。③移植后中位随访时间为22.1(19.2~24.7)个月,3年总生存(OS)率、无病生存(DFS)率分别为71.9%(95%CI 65.7%~78.6%)、63.6%(95%CI 57.2%~70.7%),3年非复发死亡率(NRM)为17.9%(95%CI 13.9%~22.9%),3年累积复发率(CIR)为9.8%(95%CI 6.7%~13.7%)。影响移植后OS的独立危险因素包括单体核型(MK)(P=0.004,HR=3.26,95%CI 1.46~7.29)、造血干细胞移植合并症指数(HCI-CI)≥3分(P<0.001,HR=2.86,95%CI 1.72~4.75)、发生Ⅱ~Ⅳ度肠道急性GVHD(P<0.001,HR=5.94,95%CI 3.50~10.10)。④MDS-IB1/IB2组移植后3年OS率、DFS率均优于MDS-biTP53组[OS:72.0%(95%CI 63.4%~80.7%)对46.4%(95%CI 26.9%~80.1%),P=0.020;DFS:67.4%(95%CI 60.3%~75.3%)对39.7%(95%CI 22.3%~70.8%),P=0.015],3年CIR低于MDS-biTP53组[7.3%(95%CI 4.3%~11.4%)对26.9%(95%CI 9.2%~48.5%),P=0.004]。MDS-IB1/IB2组、MDS-f组、MDS-biTP53组移植后3年NRM分别为16.7%(95%CI 12.1%~22.1%)、20.5%(95%CI 9.4%~34.6%)、26.3%(95%CI 9.1%~47.5%)(P=0.690)。结论allo-HSCT是MDS-EB的有效治疗手段,单体核型、HCI-CI、Ⅱ~Ⅳ度肠道急性GVHD是影响患者OS的独立危险因素。WHO 2022分类有助于区分不同亚组患者allo-HSCT后疗效,allo-HSCT能够改善MDS-f患者的不良预后,但MDS-biTP53患者移植后复发风险较高。

Objective To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with myelodysplastic syndrome accompanied by myelodysplasia(MDS-EB)and to compare the prognosis of different subtypes of patients classified by World Health Organization(WHO)2022.Methods A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study.The WHO 2022 diagnostic criteria reclassified MDS into three groups:myelodysplastic tumors with type 1/2 of primitive cell proliferation(MDS-IB1/IB2,222 cases),MDS with fibrosis(MDS-f,41 cases),and MDS with biallelic TP53 mutation(MDS-biTP53,19 cases).Their clinical data were retrospectively analyzed.Results①The median age of 282 patients was 46(15-66)years,with 191 males and 91 females.Among them,118(42%)and 164(58%)had MDS-EB1 and MDS-EB2,respectively.②Among the 282 patients,256(90.8%)achieved hematopoietic reconstruction after transplantation,with 11(3.9%)and 15(5.3%)having primary and secondary implantation dysfunctions,respectively.The cumulative incidence of acute graft-versus-host disease(GVHD)100 days post-transplantation was(42.6±3.0)%,and the cumulative incidence of gradeⅡ-Ⅳacute GVHD was(33.0±2.8)%.The cumulative incidence of chronic GVHD 1 year post-transplantation was(31.0±2.9)%.Post-transplantation,128(45.4%),63(22.3%),35(12.4%),and 17 patients(6.0%)developed cytomegalovirus infection,bacteremia,pulmonary fungal infection,and Epstein-Barr virus infection.③The median follow-up time post-transplantation was 22.1(19.2-24.7)months,and the 3-year overall survival(OS)and disease-free survival(DFS)rates were 71.9%(95%CI 65.7%-78.6%)and 63.6%(95%CI 57.2%-70.7%),respectively.The 3-year non-recurrent mortality rate(NRM)is 17.9%(95%CI 13.9%-22.9%),and the 3-year cumulative recurrence rate(CIR)is 9.8%(95%CI 6.7%-13.7%).The independent risk factors affecting OS post-transplantation include monocyte karyotype(P=0.004,HR=3.26,95%CI 1.46-7.29),hematopoietic stem cell transplantation complication index(HCI-CI)of≥3 points(P<0.001,HR=2.86,95%CI 1.72-4.75),and the occurrence of acute gastrointestinal GVHD of gradeⅡ-Ⅳ(P<0.001,HR=5.94,95%CI 3.50-10.10).④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group[OS:72.0%(95%CI 63.4%-80.7%)vs 46.4%(95%CI 26.9%–80.1%),P=0.020;DFS:67.4%(95%CI 60.3%-75.3%)vs 39.7%(95%CI 22.3%-70.8%),P=0.015].The 3-year CIR was lower than that of the MDS-biTP53 group[7.3%(95%CI 4.3%-11.4%)vs 26.9%(95%CI 9.2%-48.5%),P=0.004].The NRM at 3 years post-transplantation in the MDS-IB1/IB2,MDS-f,and MDS-biTP53 groups were 16.7%(95%CI 12.1%-22.1%),20.5%(95%CI 9.4%-34.6%),and 26.3%(95%CI 9.1%-47.5%),respectively(P=0.690).Conclusion Allo-HSCT is an effective treatment for MDS-EB,with monomeric karyotype,HCI-CI,and gradeⅡ-Ⅳacute gastrointestinal GVHD as independent risk factors affecting the patient’s OS.The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients.Allo-HSCT can improve the poor prognosis of patients with MDS-f,but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.