酪氨酸激酶抑制剂治疗期间PH(−)细胞出现克隆性染色体异常对慢性髓性白血病患者预后的影响

OBJECTIVE: To investigate the characteristics and prognosis of clonal chromosomal abnormalities appearing in Philadelphia negative metaphases (CCA/Ph(−)) cells in chronic myeloid leukemia (CML) with tyrosine kinase inhibitor (TKI) therapy. METHODS: The clinical data of 30 cases with CCA/Ph(−) during TKI treatment in Henan Cancer Hospital from August 2007 to July 2017 were retrospectively analyzed. The univariate factor was analyzed by Kaplan-Meier method. Multiple-factor was analyzed by Cox proportional risk model. RESULTS: Of the 30 cases, 19 (63.3%) were males. At the first detection of CCA/Ph(−) the median age was 44 (rang 14–68) years old and the median treatment of TKI was 13 (rang 2–94) months. The clones proportion of first detected CCA/Ph(−)≥ 50% was found in 18 (60.0%) cases. TKI treatment for 3 months with BCR-ABL(IS) less than 10% was seen in 14 (46.7%) patients. 63.3% (19/30) of CCA/Ph(−) was transient (only one time) and 36.7% (11/30) was repeated (≥2 times). Trisomy 8 dominant accounted for 60.0% (18/30), −7/7q− for 13.3% (4/30), loss of chromosome Y 6.7%. With a median of follow-up 50 months, 76.7% (23/30) cases were in complete cytogenetic response (CCyR) ; 63.3% (19/30) in major molecular response (MMR), 43.3% (13/30) in undetectable minimal residual disease (UMRD). The median event-free survival rate of (EFS) were 44 months, and 2-year and 5-year EFS were (82.1±7.3) % and (52.4±12.8) %, respectively. The median overall survival (OS) were 50 months, and 2-year and 5-year OS rates were (92.6±5.0) % and (77.2±14.7) %, respectively. Univariate analysis shows that the 2-year EFS of who in males, more than 2 times CCA/Ph(−), BCR-ABL(IS)>10% at 3 months after TKI were significantly lower than women, transient CCA/Ph(−), and BCR-ABL(IS)≤10% (P<0.05). The 2-year OS rate in whom the occurrence frequency of CCA/Ph(−) more than twice was significantly lower than those with transient CCA/Ph(−) (P<0.05). Multivariate analysis showed that CCA/Ph(−) was an independent risk factor (RR=4.741, 95%CI 1.21–18.571, P=0.018) for EFS in CML patients. CONCLUSION: Trisomy 8, −7/7q−, and −Y were the most common CCA/Ph(−) during TKI treatment, with high clones proportion of ≥50%. CCA/Ph(−) mainly occurred transiently or was permanent occasionally. CCA/Ph(−) recurrence (≥2 times) was an independent risk factor for EFS and OS in CML with TKI.