Severe hematologic toxicity and its impact on treatment response in newly diagnosed patients with chronic myeloid leukemia receiving tyrosine kinase-inhibitor therapy.
10.3760/cma.j.issn.0253-2727.2019.04.004
- Author:
Lu YU
1
;
Ya Zhen QIN
;
Yue Yun LAI
;
Hong Xia SHI
;
Xiao Jun HUANG
;
Qian JIANG
Author Information
1. Peking University People's Hospital, Peking University Institute of Hematology, Beijing 100044, China.
- Publication Type:Journal Article
- Keywords:
Hematologic toxicity;
Leukemia, myeloid, chronic, BCR-ABL (+);
Tyrosine kinase inhibitors
- MeSH:
Adolescent;
Adult;
Aged;
Aged, 80 and over;
Dasatinib;
Female;
Humans;
Imatinib Mesylate;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive;
Male;
Middle Aged;
Protein Kinase Inhibitors;
Protein-Tyrosine Kinases;
Retrospective Studies;
Treatment Outcome;
Young Adult
- From:
Chinese Journal of Hematology
2019;40(4):281-287
- CountryChina
- Language:Chinese
-
Abstract:
Objectives: To explore the incidence and factors of severe leukopenia and/or thrombocytopenia in newly diagnosed patients with chronic myeloid leukemia (CML) to probe their impacts on cytogenetic and molecular responses, progression free survival (PFS) and overall survival (OS) . Methods: Data of newly diagnosed patients with CML in the chronic phase (CP) and/or accelerated phase (AP) were retrospectively collected and analyzed. Results: 855 CML patients [including 744 (87%) in the CP and 111 (13.0%) in the AP] were included in this study. 523 (61.2%) patients were male with a median age of 39 years (range, 14-87 years) . 749 (87.6%) patients received imatinib, 93 (10.9%) nilotinib, and 13 (1.5%) dasatinib, respectively as front-line therapy. At a median treatment of 1 month (range, 0.1-7.0 months) , 137 (16.0%) developed ≥grade 3 leukopenia and/or thrombocytopenia and recovered 0.6 month (range, 0.3-6.5 months) . Multivariate analysis showed that female gender (OR=1.5, 95%CI 1.0-2.2, P=0.033) , WBC ≥100×109/L (OR=1.9, 95%CI 1.3-2.8, P=0.001) , CP in Sokal high-risk (OR=2.2, 95%CI 1.2-3.9, P=0.005) , AP with ≥15% blast cells in blood or bone marrow (OR=5.1, 95%CI 1.9-13.3, P=0.001) were factors associated with higher incidence of ≥grade 3 leukopenia and/or thrombocytopenia. Severe leukopenia and/or thrombocytopenia with time of drug discontinuance >2 weeks was associated with lower probabilities of achieving complete cytogenetic (OR=0.4, 95%CI 0.3-0.6, P<0.001) , severe leukopenia and/or thrombocytopenia, no matter the time of drug discontinuance >2 weeks or ≤2 weeks, were associated with lower probabilities of achieving major molecular responses (OR=0.3, 95%CI 0.2-0.5, P<0.001; OR=0.7, 95%CI 0.5-1.0, P=0.036) and MR4.5 (OR=0.2, 95%CI 0.1-0.5, P=0.002; OR=0.7, 95%CI 0.4-1.1, P=0.110) ; however, those had no impacts on PFS and OS. Conclusions: Severe leukopenia and/or thrombocytopenia were common adverse events during TKI therapy. Female patients, WBC ≥100×109/L at diagnosed, CP in Sokal high-risk, CML-AP with ≥15% blast cells in blood or bone marrow were at high risk for higher incidence of severe leukopenia and/or thrombocytopenia. Those severe adverse events had impacts on lower cytogenetic and molecular response.
