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

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. CONCLUSION: 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.