慢性髓性白血病患者酪氨酸激酶抑制剂治疗中发生的Ph阴性髓系肿瘤

Philadelphia chromosome-negative myeloid neoplasms in patients with Philadelphia chromosome-positive chronic myeloid leukemia during tyrosine kinase inhibtor-therapy

目的探讨Ph阳性慢性髓性白血病(Ph+CML)患者在酪氨酸激酶抑制剂(TKI)治疗中出现Ph阴性克隆性染色体异常(CCA/Ph-)后发生Ph-骨髓增生异常综合征或急性髓系白血病(MDS/AML)患者的临床特征.方法回顾性分析2001年5月至2017年12月收治的出现CCA/Ph-的CML患者资料.结果共收集63例在TKI治疗过程中检出CCA/Ph-的Ph+CML患者,其中7例发生Ph-MDS/AML,56例疾病稳定.与疾病稳定组相比,首次检出CCA/Ph-时,Ph-MDS/AML组患者血红蛋白(P=0.007)和PLT(P=0.006)水平更低,外周血原始细胞比例(P<0.001)更高;当发生MDS或AML时,Ph-MDS/AML组患者的CCA/Ph-以"-7"为主(5/7,71.4%),而Ph-疾病稳定组以"+8"为多见(32/56,57.1%).Ph-MDS/AML组患者总体预后不良,而Ph-疾病稳定组多数CCA/Ph-持续存在或有变化,大部分患者分子学反应良好,疾病稳定.结论 CML患者接受TKI治疗中,少数会发生CCA/Ph-,其中大部分病情稳定,极少数会发生Ph-MDS/AML.当出现不明原因血细胞减少或CCA/Ph-为"-7"时,应重视外周血涂片、骨髓细胞遗传学和骨髓细胞形态学检测.

Objective To compare the clinical features between the 2 cohorts developing myelodysplastic syndrome or acute myeIogenous Ieukemia in Philadelphia chromosome-negative cells (Ph- MDS/AML) and maintaining disease stable in the patients with Philadelphia chromosome-positive chronic myeloid Ieukemia (Ph+ CML) who had clonal chromosomal abnormalities in Philadelphia chromosome-negative metaphases (CCA/Ph-) during tyrosine kinase inhibtor (TKI)- therapy. Methods We retrospectively analyzed Ph+ CML patients who developed CCA/Ph- during TKI-therapy from May 2001 to December 2017. Results Data of CCA/Ph- 63 patients, including 7 progressing to Ph- MDS/AML and 56 remaining disease stable were collected. Compared with those with stable disease, patients with Ph-MDS/AML had lower hemoglobin (P=0.007) and platelet (P=0.006) counts, and higher proportion of peripheral blasts (P<0.001) when the first time CCA/Ph- was detected, and more mosonomy 7 abnormality (5/7, 71.4%) when MDS or AML was diagnosed;meanwhile, trisomy 8 (32/56, 57.1%) was more common in those with stable disease. Outcome of the patients with Ph- MDS/AML were poor. However, most of those with CCA/Ph- and stable disease had optimal response on TKI-therapy. Conclusions A few patients with Ph+ CML developed CCA/Ph- during TKI-therapy, most of them had stable disease, but very few patients developed Ph- MDS/AML with more common occurrence of monosomy 7 or unknown cytopenia. Our data suggested the significance of monitoring of peripheral blood smear, bone marrow morphology and cytogenetic analysis once monosomy 7 or unknown cytopenia occurred.