酪氨酸激酶抑制剂治疗老年Ph阳性慢性粒细胞白血病的临床观察

Application of Tyrosine Kinase Inhibitor in the Treatment of Ph-positive Chronic Myelogenous Leukemia in the Elderly

目的探究酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)治疗Ph阳性老年慢性粒细胞白血病后检出克隆演变对预后的影响,为治疗该病提供方法。方法选取2009年7月-2019年10月期间于内蒙古医科大学附属医院初诊为Ph阳性的慢性髓性白血病(CML)的老年患者780例,将一线TKI治疗后检出CCA/Ph-(Ph阴性细胞间期出现克隆性染色体异常)的32例老年Ph阳性CML患者作为研究对象。分析CML不同病期TKI疗效、TKI治疗前CML不同病期患者核型特征及克隆演变特点。结果TKI治疗于中位时间14(3~92)个月首次出现CCA/Ph-,且有11例(34.4%)调整药物为二线NL或DAS;首次伴CCA/Ph-的克隆比例≥50%有19例(59.4%),其余为<50%;12例(37.5%)反复出现CCA/Ph-,其余为一过性;CA/Ph-异常类型中以+8为主最高、-7/7q-为其次。32例患者中15例(46.9%)于初次给药3个月后检验BCR-ABLIS,其水平≤10%,随访49个月75.0%(24/32)疗效维持在CCyR,62.5%(20/32)为MMR。随访50个月时32例患者平均EFS时间为45个月,总生存中位时间为50个月。EFS率(2年)与性别、TKI给药3个月BCR-ABLIS水平和CCA/Ph-出现频率相关(P<0.05),OS率(2年)与CCA/Ph-出现频率相关(P<0.05)。影响老年CML患者EFS率的独立性危险因素是反复出现CCA/Ph-(P<0.05)。结论老年Ph阳性CML患者一线TKI治疗检出CCA/Ph-时,+8为主异常类型最为常见,-7/7q-为其次,大对数患者克隆比例超过50%,且CCA/Ph-克隆演变可一过性或反复出现,其中常见为一过性。而影响老年CML患者总生存率及无事件生存的独立性危险因素为CCA/Ph-反复性出现。

Objective To explore the influence of clonal evolution on the prognosis of Ph-positive chronic myeloid leukemia(CML)in the elderly after the treatment with tyrosine kinase inhibitors(TKI).Methods Out of 780 elderly with phpositive CML initially diagnosed during the period from July 2009 to October 2019,32 ph-positive CML elderly with CCA/phminus(abnormalities of clonal chromosomes in ph-negative intercellular phase)detected after first-line TKI treatment were enrolled in the study;the efficacy of TKI treatment for the cases with CML at different stages,the karyotype characteristics and clonal evolution characteristics of CML at different stages before TKI treatment were analyzed.Results CCA/Ph-first appeared at the median time of TKI treatment:the 14 th month(3 to 92 months)and the treatment of 11 cases(34.4%)were adjusted to second-line NL or DAS;the proportion of clones with CCA/Ph-for the first time was≥50%in 19 cases(59.4%)while the rest were<50%;CCA/Ph-occurred repeatedly in 12 patients(37.5%),and the rest were transient;in CA/ph-exception types,the main was+8(the highest)and the secondary was-7/7 q-;out of the 32 cases,15(46.9%)were tested for bcr-ablis 3 months after the initial administration and the level was≤10%;in the 49 th month of follow-up,the efficacy in 75.0%of the cases(24/32)was maintained at CCyR and the molecular response in 62.5%of the cases(20/32)was MMR;in the 50 th month of follow-up,32 cases had an average EFS time of 45 months and a median total survival time of 50 months.EFS rate(2 years)was correlated with gender,bcr-ablis level 3 months after TKI administration,and CCA/ph-occurrence frequency(P<0.05),and OS rate(2 years)was correlated with CCA/ph-occurrence frequency(P<0.05);the recurrence of CCA/Phwas the independent risk factor affecting the EFS rate in the elderly with CML(P<0.05).Conclusion+8 is the most common abnormal type followed by-7/7 q-when CCA/Ph-is detected in the first-line TKI treatment of the elderly with Ph-positive CML;the proportion of cloning in most cases is over 50%and the clonal evolution of CCA/Ph-may be transient(more common)or repeated;the independent risk factor affecting the total survival and event-free survival of the elderly with CML is the CCA/ph-recurrence.