慢性髓性白血病酪氨酸激酶抑制剂治疗后出现Ph(−)细胞染色体异常八例临床观察

OBJECTIVE: To observe the clinical features, characteristics and outcomes of chromosomal abnormalities in Philadelphia negative cells (Ph(−)CA) of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitor (TKI), and provide the evidence for clinical treatment. METHODS: We collected and analyzed the clinical and laboratory data of 8 CML patients treated in the affiliated Tumor Hospital of Zhengzhou University from September 2011 to July 2015 and Ph(−)CA occurred after TKI therapy. Karyotypes and BCR-ABL fusion genes were analyzed by R-banding and real-time quantitative polymerase chain reaction (RT-PCR), respectively. RESULTS: 6 cases were male and 2 cases were female, with a median age of 51 (31–75) years old. 6 patients had low Sokal risk scores and 2 had intermediate scores. 4 cases of Ph(−)CA occurred with imatinib, 1 case with dasatinib and 3 cases with nilotinib. The median duration of Ph(−)CA appearance was 12.0 (1.7–34.5) months since taking TKI. Chromosomal abnormality +8 was the most common type in Ph(−)CA, which accounted for 50.0%, followed by −7 (25.0%). When found Ph(−)CA, all patients had complete hematologic response (CHR), but none got main molecular response (MMR). The Ph(−)CA had gone in 7 cases at the end of follow-up and the median duration was 6.2 (2.5–31.5) months. After Ph(−)CA disappeared, 1 patient obtained MMR and 2 cases achieved complete molecular response (CMR), but Ph(+) clone recurred in 1 case. CONCLUSION: Ph(−)CA can be found in CML patients treated with imatinib, dasatinib and nilotinib, and +8 is the most common Ph(−)CA. So detection of karyotype is significant during treatment. Although most Ph(−)CA can disappear, −7/7q− or other complex karyotypes should be monitored closely.