Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes.
10.3760/cma.j.issn.0253-2727.2023.04.006
- Author:
Zi Yu LI
1
;
Ya Zhen QIN
1
;
Yue Yun LAI
1
;
Hong Xia SHI
1
;
Yue HOU
1
;
Xiao Shuai ZHANG
1
;
Qian JIANG
1
Author Information
1. Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.
- Publication Type:Journal Article
- Keywords:
Cytopenia;
Leukemia, myeloid, chronic;
Treatment outcome;
Tyrosine kinase inhibitors
- MeSH:
Humans;
Male;
Adolescent;
Adult;
Female;
Protein Kinase Inhibitors/therapeutic use*;
Tyrosine Protein Kinase Inhibitors;
Treatment Outcome;
Retrospective Studies;
Dasatinib/therapeutic use*;
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*;
Leukemia, Myeloid, Chronic-Phase/drug therapy*;
Thrombocytopenia
- From:
Chinese Journal of Hematology
2023;44(4):295-301
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.
