Abstract
Objective: To investigate the effects of additional chromosomal abnormalities (ACA) in Philadelphia chromosome-positive (Ph(+)) cells on biological characteristics, therapy efficacy, and prognosis of patients with primary chronic myeloid leukemia (CML) -chronic phase (CP) and those who developed CML-accelerated phase/blast phase (AP/BP) during therapy. Methods: The clinical data of 410 patients with Ph(+) CML, including 348 patients with primary CML-CP and 62 patients who progressed to CML-AP/BP during treatment, who were admitted to Henan People's Hospital from January 2013 to June 2020 were retrospectively analyzed to categorize into high-risk, non-high-risk, and non-ACA groups according to the ELN2020 criteria. The effects of high- and non-high-risk ACA on biological characteristics, therapy efficacy, and prognosis were compared. Results: ①Among the 348 patients with primary CML-CP, 20 patients (5.75% ) had ACA, including 3 and 17 patients with high-risk and non-high-risk ACA, respectively, whereas the remaining 328 patients did not have ACA. There were no significant differences in baseline clinical characteristics between those with and without ACA (P>0.05 for all) . The rates of complete hematological response, complete cytogenetic response, major molecular remission, and 5-year overall survival (OS) were not significantly different between the non-high-risk ACA and non-ACA groups (P>0.05 for all) ; however, the 5-year progression-free survival of the non-high-risk ACA group (42.0% ) was significantly lower than that of the non-ACA group (74.5% ) (χ(2)=4.766, P=0.029) .②Of the 62 patients who progressed to CML-AP/BP during treatment, 41 patients (66.13% ) had ACA, including 28 and 13 patients with high-risk and non-high-risk ACA, respectively, whereas the remaining 21 patients did not have ACA. Platelet counts of the high-risk ACA group (42.5×10(9)/L) were lower than those of the non-high-risk (141×10(9)/L) and non-ACA groups (109×10(9)/L) (χ(2)=4.968, P=0.083) . There was no significant difference in the incidence of point mutations in ABL kinase among the three groups (P=0.652) . The complete cytogenetic response of the high-risk ACA group (5.3% ) was significantly lower than that of the non-ACA group (46.7% ) (χ(2)=5.851, P=0.016) . The 5-year OS of the high-risk ACA group was lower than that of the non-ACA group (46.2% vs 77.8% , χ(2)=3.878, P=0.049) . Subgroup analysis revealed that the 5-year OS rate of the high-risk group Ⅱ, which included -7/7q-, i (17q) , and complex karyotype comprising ≥2 high-risk ACA, was significantly lower than that of the non-ACA group (28.6% vs 77.8% , χ(2)=8.035, P=0.005) whereas the 5-year OS rate was not significantly different between high-risk group Ⅰ, which included +8,+Ph, and complex ACA with +8/+Ph, and the non-ACA group (54.5% vs 77.8% , χ(2) =1.514, P=0.219) . Conclusion: Due to different disease stages and ACA/Ph(+) types, treatment response and prognosis vary among patients with CML harboring ACA/Ph(+). The emergence of high-risk ACA during therapy suggests worse therapy efficacy and prognosis. Strict and standardized cytogenetic monitoring is critical for early detection, precise diagnosis, and treatment of these patients.