Prognosis of clonal chromosomal abnormalities in Philadelphia negative metaphases cells in chronic myeloid leukemia with tyrosine kinase inhibitor therapy
10.3760/cma.j.issn.0253-2727.2019.03.009
- VernacularTitle: 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
- Author:
Huifang ZHAO
1
;
Yanli ZHANG
;
Jieying HU
;
Zhen LI
;
Jian ZHOU
;
Fengkuan YU
;
Yingling ZU
;
Hu ZHOU
;
Xudong WEI
;
Yongping SONG
Author Information
1. Department of Hematology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, China
- Publication Type:Journal Article
- Keywords:
Leukemia, myelogenous, chronic, BCR-ABL positive;
Chromosomal abnormalities;
Philadelphia negative cells;
Tyrosine kinase inhibitors;
Prognosis
- From:
Chinese Journal of Hematology
2019;40(3):209-214
- CountryChina
- Language:Chinese
-
Abstract:
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.
