Prognosis of clonal chromosomal abnormalities in Philadelphia negative metaphases cells in chronic myeloid leukemia with tyrosine kinase inhibitor therapy

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-ABLIS 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-ABLIS>10% at 3 months after TKI were significantly lower than women, transient CCA/Ph-, and BCR-ABLIS≤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. Key words: Leukemia, myelogenous, chronic, BCR-ABL positive; Chromosomal abnormalities; Philadelphia negative cells; Tyrosine kinase inhibitors; Prognosis