Ph阳性慢性粒细胞白血病患者伊马替尼治疗后的Ph阴性异常克隆演变

Clonal evolution of abnormal Philadelphia chromosome-negative cells after imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia

目的观察Ph阳性慢性粒细胞白血病(Ph+CML)患者在伊马替尼治疗后的Ph阴性异常克隆演变(Ph-CE)。方法对100例伊马替尼单药治疗有效的Ph+CML患者(其中干扰素治疗失败的慢性期患者54例、加速期患者37例、急变期患者9例)在治疗前及治疗后18～30个月内定期监测其细胞染色体核型变化(G显带方法)。结果11例(11%)患者于治疗后3～29个月一过性、间断或连续检出Ph-CE,其中慢性期患者5例、加速期患者5例、急变期患者1例。Ph-CE见于Ph+克隆开始减少时或在Ph+克隆消失之后,同期Ph-CE细胞的比例与Ph+细胞的比例呈负相关(P<0.05)。Ph-CE多为+8(5例,45.5%)和+Y(3例,27.3%),5例患者同时伴有Ph+细胞染色体附加异常。Ph-CE者中,7例获得主要遗传学缓解,9例获得完全血液学缓解。在观察期内,1例加速期患者在持续治疗20个月时进展至急变期。结论Ph+CML患者经伊马替尼治疗后获得不同程度遗传学缓解时约11%被检出Ph-CE,但在随访期内大多数患者未显示病情进展。

Objective To investigate clonal evolution of abnormal Philadelphia chromosome-negative cells (Ph-CE) after imatinib mesylate therapy in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+CML). Methods Bone marrow cells G-banding karyotype was evaluated every 3 months in 100 patients with Ph+ CML after achieving hematologic responses on the course of imatinib therapy. There were 54 patients in chronic phase (CP), 37 in accelerated phase (AP) and 9 in blast phase(BP). Results After a median follow-up of 32 months (ranged 25—34 months), 11 patients, including 5 cases in CP, 5 in AP and 1 in BP, developed transient, interrupted or continuous Ph-CE after 3—29 months on imatinib therapy. Ph-CE emerged at the beginning of Ph+ cells decreasing or after Ph+ cells disappearing. The proportion of Ph-CE, was negatively correlated with the proportion of Ph+ cells (P<0.05). Ph-CE commonly included +8 (45.5%) and +Y (27.3%). Five patients had additional cytogenetic abnormalities besides Ph+ in Ph-CE. Seven of the patients with Ph-CE achieved a major cytogenetic response while 9 of them achieved a complete hematologic response. One patient with Ph-CE in AP progressed to BP 20 months after the initiation of the therapy while the rests remained in hematologic or cytogenetic responses. Conclusion Ph-CE occured in about 11% of the patients with Ph+ CML who achieved major or minor cytogenetic responses on imatinib therapy. After a median follow-up of more than 2 years, most of the patients with Ph-CE were in a stable status with no disease progression.