急性早幼粒细胞白血病患者PML/RARα融合基因首次转阴时间及其临床意义探讨

The First Switched Time of PML/RARa Fusion Gene in Patients with Acute Promyelocytic Leukemia and Its Clinical Significance

目的:为了观察和分析急性早幼粒细胞白血病(acute promyelocytic leukemia,APL)PML/RARα融合基因首次转阴时间和首次转阴时间长短的临床意义。方法:选取我院初诊APL患者60例,按照APL临床路径行诱导缓解及缓解后巩固治疗和维持治疗;应用多重巢式PCR动态监测APL患者PML/RARα融合基因的表达水平变化,计算首次转阴时间,随访观察并评价首次转阴时间的临床意义。结果:除3例死亡和1例失访外,其余56例初诊APL患者经正规治疗后,其PML/RARα融合基因均在24至381 d之间首次转阴,平均首次转阴时间为(131±90)d。首次转阴时间在PML/RARα融合基因不同亚型之间存在差异,L型转阴时间较S型的短(P=0.032),而不同年龄、性别、危险度分层组别之间差异均无统计学意义。首次转阴后的56例患者分别随访25 d至1979 d,中位随访时间为946 d,其中1例133 d首次转阴患者维持3个月后转阳并且随后出现临床复发,其余55例患者均长期保持分子水平缓解。结论:初诊APL患者PML/RARα融合基因平均约在正规治疗后4个月首次转阴;不同基因亚型之间首次转阴时间存在差异。PML/RARα融合基因首次转阴时间可客观反映APL患者治疗后白血病细胞的消减水平,对临床治疗有提示作用,但不能作为判断预后的绝对依据;以PML/RARα融合基因动态监测微小残留病灶对分析APL复发具有重要的临床意义。

Objective:To investigate the first switched time of PML/RARα fusion gene in patients with acute promyelocytic leukemia(APL) and its clinical significance.Methods:sixty cases of newly diagnosed APL were enrolled in this study.They received standard remission induction,consolidation and maintenance treatments according to the clinical pathway for APL,and were followed up.During the same time the PML/RARα fusion gene mRNA expression of all cases was detected by multi-nested PCR.Results:except for 3 death cases and 1 case failed to follow-up,the PML/RARα fusion genes in the remaining 56 cases were firstly found to be negative from 24 to 381 days respectively,the mean value of the first switched time was 131 ±90 days.There was no statistically significant difference in age,sex and risk stratification between different groups.However,the cases with L-type PML/RARα gene had shorter time compared with the patients with S-type PML/RARα gene(P = 0.032);then,for the above-mentimed 56 cases,the follow-up duration ranged from 25-1979 days(median 946 days),long-term molecular remissions had been observed in most cases,but 1 case with the first switched time of 133 days unfortunately recurred to be positive and followed by clinical relapse.Conclusion:The PML/RARα fusion gene in newly diagnosed APL patients was first switched to be negative in about 4 months after treatment.The first switched time of PML/RARα fusion gene can objectively reflect the reduction of leukemia cells,and the differences among different subtypes of PML/RARα fusion gene may have some suggestions for the treatment,but without important significance for the evaluation of prognosis and recurrence for APL patients.In addition,minimal residual disease(MRD) can be dynamically monitored by detecting PML/RARα fusion gene,thus having an important clinical significance for analysis of APL recurrence.