异基因造血干细胞移植治疗高危多发性骨髓瘤临床分析

Allogeneic hematopoietic stem cell transplantation for high⁃risk multiple myeloma patients:a clinical analysis

目的探讨异基因造血干细胞移植(allo-HSCT)治疗高危多发性骨髓瘤(MM)的效果和预后影响因素。方法回顾性分析2003年4月至2017年3月海军军医大学附属长征医院44例确诊并行allo-HSCT的高危MM患者临床资料。分析患者总有效率、复发率、非复发相关死亡(NRM)率、移植物抗宿主病(GVHD)发生率等;采用Kaplan-Meier法分析患者移植后总生存(OS)、无进展生存(PFS);采用Cox比例风险模型对预后影响因素进行回归分析。结果44例患者移植后有38例可评估疗效。中位随访时间111个月(0~216个月),其中22例生存,22例死亡,21例复发。移植前完全缓解(CR)率29.5%(13/44),非常好的部分缓解(VGPR)率45.5%(20/44),部分缓解(PR)率22.7%(10/44),疾病稳定(SD)率2.3%(1/44);移植后CR率71.1%(27/38),VGPR率13.2%(5/38),PR率13.2%(5/38),疾病进展(PD)率2.6%(1/38)。5年OS率、PFS率分别为51.8%、47.8%,10年OS率、PFS率分别为51.3%、43.1%。5、10年累积疾病复发率分别为38.6%、45.4%,5年累积NRM率为25.0%。急性GVHD发生率为38.6%(17/44),其中3~4级急性GVHD发生率为6.8%(3/44);慢性GVHD发生率为27.3%(12/44)。移植前使用硼替佐米(HR=3.461,95%CI 1.211~9.880,P=0.020)和移植后感染(HR=0.283,95%CI 0.098~0.819,P=0.020)是移植后OS的独立影响因素。结论allo-HSCT能够克服MM高危因素,是高危MM患者值得尝试的治疗手段。移植前使用硼替佐米和移植后感染可能是高危MM患者移植后OS的重要影响因素。

Objective To investigate the effects of allogeneic hematopoietic stem cell transplantation(allo⁃HSCT)in treatment of high⁃risk multiple myeloma(MM)patients and its influencing factors of the prognosis.Methods The clinical data of 44 high⁃risk MM patients treated with allo⁃HSCT in Changzheng Hospital Affiliated of Naval Military Medical University from April 2003 to March 2017 were retrospectively analyzed.The overall response rate(ORR),relapse rate,non⁃relapse⁃related death(NRM)rate,graft⁃versus⁃host disease(GVHD)incidence of patients were also analyzed.Kaplan⁃Meier was used to analyze the overall survival(OS)rate and progression⁃free survival(PFS)rate after transplantation.Cox proportional hazard model was used to make regression analysis of the factors affecting the prognosis.Results Among 44 patients,38 cases could be evaluated for efficacy after transplantation.The median follow⁃up time was 111 months(0-216)months,22 cases survived,22 cases died,21 cases relapsed.Before transplantation,complete remission(CR)rate was 29.5%(13/44),very good partial remission(VGPR)rate was 45.5%(20/44),partial remission(PR)rate was 22.7%(10/44),stable disease(SD)rate was 2.3%(1/44);After transplantation,CR rate was 71.7%(27/38),VGPR rate was 13.2%(5/38),PR rate was 13.2%(5/38),the progression of the disease(PD)rate 2.6%(1/38).The 5⁃year OS rate and PFS rate was 51.8%and 47.8%,the 10⁃year OS rate and PFS rate was 51.3%and 43.1%,respectively;the 5⁃year and 10⁃year cumulative disease relapse rate was 38.6%and 45.4%,the 5⁃year cumulative NRM rate was 25.0%.Acute GVHD rate was 38.6%(17/44)and grade 3⁃4 acute GVHD rate was 6.8%(3/44);chronic GVHD rate was 27.3%(12/44).Cox univariate and multivariate analysis showed that the use of bortezomib before transplantation(HR=3.461,95%CI 1.211-9.880,P=0.020)and post⁃transplant infection(HR=0.283,95%CI 0.098-0.819,P=0.020)were independent factors affecting OS after transplantation.Conclusions Allo⁃HSCT can overcome the high⁃risk factors of MM and is worth to try for high⁃risk MM patients.The use of bortezomib before transplantation and post⁃transplant infection can be important factors affecting OS after transplantation.