摘要
目的:探讨骨髓纤维化(MF)程度对骨髓增生异常综合征(MDS)患者临床特征、去甲基化药物(HMA)疗效及生存的影响。方法:回顾性分析2016年1月1日至2021年7月15日山西医科大学第二医院血液科收治的103例初发且接受HMA治疗的MDS患者的临床资料,依据骨髓活检纤维化程度将患者分为MDS-MF0、MDS-MF1、MDS-MF2/33组,比较3组患者的临床特征、疗效及生存差异,运用logistic回归和Cox回归法分析影响疗效及预后的相关因素。结果:103例MDS患者中,有60例(58.2%)未合并MF(MDS-MF0),28例(27.2%)合并轻度MF(MDS-MF1),15例(14.6%)合并中重度MF(MDS-MF2/3)。MDS-MF0、MDS-MF1、MDS-MF2/33组患者的中位血红蛋白(Hb)具有统计学差异(P=0.016),-5/del(5q)染色体改变的患者比例在3组间的差异也有统计学意义(P=0.046)。共97例患者纳入疗效分析,总反应率(ORR)为62.9%。MDS-MF0、MDS-MF1、MDS-MF2/33组患者的ORR分别为72.2%、53.6%、46.7%,差异无统计学意义(P=0.093)。MDS合并MF患者的ORR为51.2%,与MDS-MF0相比,差异有统计学意义(P=0.033)。多因素分析结果显示,治疗疗程数≥4个是影响HMA治疗总反应的独立有利因素(OR=7.532,95%CI:2.031-27.938,P=0.003),骨髓纤维化程度不影响疗效(P>0.05)。至随访截止,101例纳入生存分析的患者中,27例(26.7%)转化为白血病,共75例(74.3%)死亡,19例(18.8%)仍存活,7例(6.9%)失访,中位总生存期(OS)为21.4个月,中位无进展生存期(PFS)为10.3个月,中位无白血病生存期(LFS)为18.1个月。MDS-MF0、MDS-MF1、MDS-MF2/33组的中位OS分别为27.9、12.2和11个月(P=0.017),中位PFS分别为13.5、9.1和6.4个月(P=0.025),中位LFS分别为24.5、11和11个月(P=0.020)。对于MDS伴低原始细胞(MDS-LB)患者,伴MF与不伴MF患者间OS与LFS差异有统计学意义(OS:P=0.024;LFS:P=0.026),PFS差异无统计学意义(P=0.057)。多因素分析结果显示,骨髓原始细胞比例升高、复杂核型是影响患者OS的独立危险因素,治疗疗程数≥4个是影响患者OS的独立保护因素,骨髓纤维化程度不具有独立预后意义。结论:合并中重度骨髓纤维化的MDS患者贫血更重、-5/del(5q)染色体异常更常见。存在骨髓纤维化的患者对HMA治疗的总体反应率较低,但不同骨髓纤维化程度的MDS患者对HMA治疗的总体反应率没有明显差异。在HMA治疗背景下,骨髓纤维化对MDS患者的生存有不利影响,但不具有独立预后意义。
Objective:To investigate the effect of the degree of myelofibrosis(MF)on clinical characteristics,therapeutic efficacy of hypomethylating agents(HMA)and survival in patients with myelodysplastic syndromes(MDS).Methods:The clinical data of 103 patients with newly diagnosed MDS who received HMA treatment in the Department of Hematology of the Second Hospital of Shanxi Medical University from January 1,2016 to July 15,2021 were retrospectively analyzed.The patients were divided into three groups according to the degree of fibrosis in bone marrow biopsy:MDS-MF0,MDS-MF1,and MDS-MF2/3.The clinical characteristics,efficacy and survival were compared among three groups.Logistic regression and Cox regression analyses were employed to identify factors affecting the efficacy and prognosis.Results:Among 103 MDS patients,60 cases(58.2%)had no myelofibrosis(MDS-MF0),28 cases(27.2%)had mild myelofibrosis(MDS-MF1),and 15 cases(14.6%)had moderate to severe myelofibrosis(MDS-MF2/3).The median hemoglobin(Hb)of patients in the MDS-MF0,MDS-MF1,and MDS-MF2/3 groups showed statistical differences(P=0.016),and the proportion of patients with-5/del(5q)also showed statistical differences among the three groups(P=0.046).A total of 97 patients were included in the efficacy analysis,with an overall response rate(ORR)of 62.9%.The ORRs of the MDS-MF0,MDS-MF1,and MDS-MF2/3 groups were 72.2%,53.6%and 46.7%,respectively,with no statistically significant difference(P=0.093).The ORR in MDS patients combined with MF was 51.2%,which was statistically significantly different from that in MDS-MF0 patients(P=0.033).Multivariate analysis showed that more than 4 cycles of treatment was an independent favorable factor affecting the overall response to HMA therapy(OR=7.532,95%CI:2.031-27.938,P=0.003),while the degree of myelofibrosis did not affect the efficacy(P>0.05).By the end of follow-up,among 101 patients included in the survival analysis,27 cases(26.7%)transformed into leukemia,a total of 75 cases(74.3%)died,19 cases(18.8%)remained alive,and 7 cases(6.9%)were lost to fllow-up.The median overall survival(OS)was 21.4 months,the median progression-free survival(PFS)was 10.3 months,and the median leukemia-free survival(LFS)was 18.1 months.In the MDS-MF0,MDS-MF1,and MDS-MF2/3 groups,the median OS was 27.9,12.2 and 11 months(P=0.017),respectively;the median PFS was 13.5,9.1 and 6.4 months(P=0.025),respectively;and the median LFS was 24.5,11 and 11 months(P=0.020),respectively.For MDS patients with low blast(MDS-LB),there were statistically significant differences in OS and LFS between those with and without MF(OS:P=0.024,LFS:P=0.026),while no significant difference was observed in PFS(P=0.057).Multivariate analysis showed that an increased proportion of bone marrow blasts and complex karyotype were independent risk factors for OS,while more than 4 cycles of treatment was an independent protective factor for OS.The degree of myelofibrosis did not have independent prognostic significance.Conclusion:MDS patients with moderate to severe myelofibrosis have more severe anemia and more common-5/del(5q)chromosome abnormalities.MDS patients with myelofibrosis had a lower ORR to HMA therapy,but there was no significant difference in ORR among MDS patients with different degrees of myelofibrosis.In the context of HMA treatment,the myelofibrosis has an adverse effect on the survival of MDS patients,though it did not show independent prognostic significance.
作者
李瑞萍
马艳萍
LI Rui-Ping;MA Yan-Ping(The Second Clinical Medical College of Shanxi Medical University;Department of Hematology,The Second Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China)
出处
《中国实验血液学杂志》
北大核心
2026年第1期142-153,共12页
Journal of Experimental Hematology
