功能性高危骨髓瘤患者的临床特征及预后分析

Clinical features and prognosis of patients with functional high-risk myeloma

目的分析功能性高危骨髓瘤(functional high-risk myeloma,FHR)患者的临床特征及影响预后的因素。方法纳入2017年1月~2022年5月在哈尔滨医科大学附属第二医院血液科收治的53例从诊断至出现复发和诱导欠佳的多发性骨髓瘤(multiple myeloma,MM)患者,根据复发时间,将≤12个月出现复发的24例MM患者归为FHR组,>12个月出现复发的29例患者归为对照组。统计分析2组患者的性别、年龄和临床资料,用Logistic回归模型逐步法筛选危险因素,筛选出有意义的临床指标并采用多因素分析探讨早期复发的高危因素。此外,将初诊时具有高危细胞遗传学异常(high-risk cytogenetic abnormality,HRCA)的患者归为基因高危组(genome high risk group,GHR组),其余未具有HRCA的患者根据疾病复发时间再分组,分为修订-功能性高危(revised-functional high risk group,R-FHR组)(≤12个月)和标准风险(standard risk group,SR组)(>12个月),采用Kaplan-Meier法绘制生存曲线,分析复发时间对总体生存率(overall survival,OS)的影响。结果(1)与对照组比较,FHR组患者合并髓外病变(extramedullary disease,EMD)的发生率更高(16.67%vs 0.00%,P=0.022);初诊时具有HRCA比例显著高于对照组(41.67%vs 13.79%,P=0.022);FHR组患者与对照组经一线治疗后≥非常好的部分缓解(very good partial response,VGPR)率、总缓解率(overall response rate,ORR)分别为20.83%vs 82.76%、87.5%vs 100%,前者疗效较差,≥VGPR率两组间比较差异具有统计学意义(P<0.001)。(2)所有患者的中位随访时间32.08(23.87~44.03)个月。FHR组患者与对照组患者中位OS分别为24.0个月vs 65.8个月(P<0.05)。(3)在53例MM患者中,GHR组患者14例,R-FHR组患者14例,SR组患者25例,经生存性分析显示,SR、R-FHR和GHR 3组的中位OS分别为65.8个月、23.0个月和32.0个月(P<0.05)。结论FHR患者对初始治疗反应差,合并髓外病变比例高,即使排除任何高危细胞遗传学因素,总体生存时间仍明显缩短,需要临床医生高度关注。

Objective To analyze the clinical features and prognostic factors of patients with functional high-risk myeloma(FHR).Methods From January 2017 to May 2022,53 patients with multiple myeloma(MM)admitted to the Department of Hematology of the Second Affiliated Hospital of Harbin Medical University from diagnosis to recurrence and poor induction were included.According to the recurrence time,MM patients with recurrence less than 12 months were classified as FHR group(n=24),and those with recurrence more than 12 months were classified as control group(n=29).The sex,age and clinical data of patients in the two groups were statistically analyzed,and the risk factors were screened by Logistic regression model step by step,and meaningful clinical indicators were screened out.The high risk factors of early recurrence were discussed by multivariate analysis.In addition,patients with high-risk cytogenetic abnormality(HRCA)at the time of initial diagnosis were classified as gene high-risk(GHR)group,and the rest patients without HRCA were regrouped according to the recurrence time of the disease.They were divided into revised-functional high risk(R-FHR)group(≤12 months)and standard risk(SR)group(>12 months).Kaplan-Meier method was used to draw the survival curve,and the influence of recurrence time on overall survival(OS)was analyzed.Results(1)Compared with the control group,the incidence of extramedullary disease(EMD)in FHR group was higher(16.67%vs 0.00%,P=0.022).The proportion of patients with HRCA at initial diagnosis was significantly higher than that of the control group(41.67%vs 13.79%,P=0.022).After first-line treatment,the very good partial response,VGPR)rate and the overall response rate(ORR)of patients in FHR group and control group were 20.83%vs 82.76%and 87.5%vs 100%,respectively.The former had poor curative effect,and the difference between the two groups was statistically significant(P<0.001);(2)The median follow-up time of all patients was 32.08(23.87~44.03)months.The median OS of patients in FHR group and control group was 24.0 months vs 65.8 months respectively(P<0.05);(3)Among 53 patients with MM,there were 14 patients in GHR group,14 patients in R-FHR group and 25 patients in SR group.Survival analysis showed that the median OS of SR,R-FHR and GHR groups was 65.8 months,23.0 months,and 32.0 months,respectively(P<0.05).Conclusion FHR patients have poor response to initial treatment and a high proportion of extramedullary lesions.Even if any high-risk cytogenetic factors are excluded,the overall survival time is still significantly shortened,which requires clinicians'high attention.