伴有核仁磷酸蛋白1突变的老年急性髓系白血病患者的临床特征及预后因素分析

Clinical characteristics and prognostic factors of elderly patients with acute myeloid leukemia with NPMl mutation

目的观察并分析伴有核仁磷酸蛋白1(NPM1)突变的老年急性髓系白血病(AML)患者的临床特征,探讨NPM1突变(NPM1+)对老年AML患者治疗和预后的影响。方法收集28例NPM1+的老年AML患者初诊时的临床资料,分析老年AML患者生存的影响因素及FLT3-ITD基因突变(FLT3+)对患者治疗有效率的影响。结果28例患者初诊时的中位白细胞(WBC)为50.0×109/L,血小板计数为45.0×109/L,其中,高WBC者20例。FAB分型中,M1型8例,M2型8例,M4型3例,M5型8例,M6型1例。所有患者的染色体核型均正常,11例患者合并FLT3+。经过1~2个疗程的诱导化疗后,28例患者的治疗有效率为64.29%(18/28),且合并FLT3+患者的化疗有效率低于合并FLT3-的患者。合并FLT3+患者的1年总生存(OS)时间明显短于合并FLT3-的患者,而诱导化疗后达完全缓解(CR)或部分缓解(PR)患者的1年OS率高于疾病未缓解(NR)的患者。初诊WBC计数较高、血小板计数较低的患者的OS率均较差。Logistic多因素回归分析结果显示,诱导化疗是老年NPM1+AML患者生存的独立影响因素(P﹤0.01)。结论在老年AML患者中,NPM1基因突变多见于高WBC、正常染色体核型的患者,且较高比例的患者合并FLT3+。伴有NPM1+的老年AML患者的远期生存率仍较低,NPM1+的预后意义尚不明确。合并FLT3+的患者的化疗有效率低,初诊WBC计数较高、血小板计数较低的患者的1年OS率均较低,诱导化疗无效是伴有NPM1+的老年AML患者预后的独立危险因素。

Objective To observe and analyze the clinical characteristics of elderly patients of acute myeloid leukemia(AML)with nucleophosmin 1(NPM1)mutation,and further explore the effects of positive NPM1 mutation(NPM1+)on the treatment and prognosis of elderly AML patients.Method The clinical data of 28 elderly AML patients(≥60 years old)with NPM1+at first visit were collected.Factors associated with AML patients’survival,and the influence of FLT3-ITD gene mutation(FLT3+)on the treatment efficiency were analyzed.Result The median white blood cell(WBC)count at the first visit of the 28 patients was 50.0×109/L,and blood platelet count was 45.0×109/L,among them,20 cases were with high WBC count(WBC>30×109/L).According to FAB classification,this cohort was stratified as follows:M18 cases,M28 cases,M43 cases,M58 cases,M61 case.All patients were with normal chromosome karyotype.There were 11 patients with FLT3+.After 1-2 courses of induced chemotherapy,a response rate of 64.29%(18/28)was achieved in 28 cases,and the response rate observed among patients with FLT3+was lower compared to those with FLT3-.The 1-year overall survival(OS)rate in patients with FLT3+was significantly lower than that in patients with FLT3-,and the 1-year OS rate in patients with complete response(CR)or partial response(PR)after induced chemotherapy was higher compared to those who had no response(NR).The OS rate of patients with higher WBC and lower blood platelet count at first visit were generally poor.Logistic multivariate regression analysis showed that,induction chemotherapy was an independent influencing factor for survival of elderly patients with NPM1+AML.Conclusion In the elderly patients with AML,the mutation of NPM1 gene is primarily found in patients with high WBC and normal chromosome karyotype,and an elevated percentage of patients with FLT3+is noted.However,the long-term survival rate of elderly patients with NPM1+AML is still low,nevertheless the prognostic significance of NPM1+was indeterminate.The response rate to chemotherapy is compromised among those with FLT3+,furthermore,the 1-year OS rate of FLT3+patients with high WBC and low blood platelet count stays in a low level.Failure to induce chemotherapy is an independent risk factor for the prognosis of elderly patients with NPM1+AML.