Inhibitors in Chronic Myeloid Leukemia

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 16 July 2024 | Viewed by 3522

Special Issue Editors


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Guest Editor
Haematology Research Centre, Department of Immunology and Inflammation, Imperial College London, London E4 7RW, UK
Interests: leukemia

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Guest Editor
Peking University People's Hospital, Beijing 100044, China
Interests: CML; MPN; AML; ALL

Special Issue Information

Dear Colleagues,

Chronic myeloid leukemia was identified as a chromosomal abnormality disease over 80 years ago in 1960. Targeted therapy, tyrosine kinase inhibitors, is the hallmark of chronic myeloid leukemia treatment. Patients could expect a comparable normal lifespan to the general people under the effective treatment strategies and patients who complete response to the medications. However, insights into the molecular mechanisms of pathogenesis, dealing with adverse events, therapeutic options for the patients in different disease stages and risk or for those without proper response to the available drugs, etc. still need deep understanding.

The aim of this special issue will focus on publishing high-quality works that are related to the understanding of the mechanisms of leukemogenesis, pathophysiology, diagnosis, and treatment of chronic myeloid leukemia with kinase or potential targets with inhibitors.  

Prof. Dr. Robert Peter Gale
Prof. Dr. Qian Jiang
Guest Editors

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Keywords

  • chronic myeloid leukemia
  • pathogenesis
  • diagnosis
  • treatment
  • inhibitor
  • tyrosine-kinase inhibitor
  • adverse events

Published Papers (3 papers)

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14 pages, 4162 KiB  
Article
A Multicenter Retrospective Chart Review Study of Treatment and Disease Patterns and Clinical Outcomes of Patients with Chronic-Phase Chronic Myeloid Leukemia in Third-Line Treatment or with T315I Mutation
by Franck-Emmanuel Nicolini, Françoise Huguet, Lynn Huynh, Churong Xu, Christophe Bouvier, Aurore Yocolly and Gabriel Etienne
Cancers 2023, 15(16), 4161; https://doi.org/10.3390/cancers15164161 - 18 Aug 2023
Cited by 1 | Viewed by 1166
Abstract
This retrospective chart review study investigated the clinical burden of adult patients with chronic-phase chronic myeloid leukemia (CP-CML) treated at three centers in France (2006–2021) who failed on two or more tyrosine kinase inhibitors (TKIs; third-line [3L]+ cohort) or harbored the BCR::ABL1 T315I [...] Read more.
This retrospective chart review study investigated the clinical burden of adult patients with chronic-phase chronic myeloid leukemia (CP-CML) treated at three centers in France (2006–2021) who failed on two or more tyrosine kinase inhibitors (TKIs; third-line [3L]+ cohort) or harbored the BCR::ABL1 T315I mutation (T315I cohort). In the 3L+ cohort (N = 157; median age at diagnosis, 56 years), TKIs received in 3L (median duration: 17 months) were dasatinib (32%), nilotinib (19%), imatinib (18%), ponatinib (17%), and bosutinib (14%). Of the 145 patients with documented responses in 3L, 42% experienced major molecular response (MMR) at 12 months. Median event-free survival [95% confidence interval] was 53.6 [44.0, 67.5] months, and median progression-free survival and overall survival (OS) were not reached. Achieving MMR in 3L was associated with a decreased mortality risk. In the T315I cohort (N = 17; 52 years), 41% of patients received five or more lines of therapy. Following identification of the T315I mutation, ponatinib was the most common TKI used (59%); the median [interquartile range] OS was 5 [3–10] years. The most common adverse events were infections (3L+ cohort) and thrombocytopenia (T315I cohort) (both 18%). Well-tolerated therapies that achieve durable responses are needed in 3L or earlier to improve CP-CML prognosis. Full article
(This article belongs to the Special Issue Inhibitors in Chronic Myeloid Leukemia)
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12 pages, 1236 KiB  
Article
Front-Line Tyrosine Kinase Inhibitors in Pediatric Chronic Myeloid Leukemia: A Study on Efficacy and Safety
by Jae Won Yoo, Suejung Jo, Moon Bae Ahn, Seongkoo Kim, Jae Wook Lee, Myungshin Kim, Bin Cho and Nack-Gyun Chung
Cancers 2023, 15(15), 3862; https://doi.org/10.3390/cancers15153862 - 29 Jul 2023
Cited by 1 | Viewed by 722
Abstract
We conducted a retrospective study on 51 pediatric patients with newly diagnosed chronic myeloid leukemia chronic phase or accelerated phase. The patients were classified into the IMA group (N = 33), treated with imatinib, and the DSA group (N = 18), treated with [...] Read more.
We conducted a retrospective study on 51 pediatric patients with newly diagnosed chronic myeloid leukemia chronic phase or accelerated phase. The patients were classified into the IMA group (N = 33), treated with imatinib, and the DSA group (N = 18), treated with dasatinib, as front-line tyrosine kinase inhibitors (TKIs). At 12 months, the rates of complete cytogenetic response were similar between the IMA group (92.3%) and DSA group (100%) (p = 0.305). However, the rate of early molecular response was higher in the DSA group than in the IMA group (100.0% vs. 80.0%, p = 0.043). By 12 and 24 months, the DSA group showed faster and higher cumulative rates of both major (DSA group: 72.2% and 100%, respectively; IMA group: 41.2% and 68.7%, respectively; p = 0.002) and deep molecular responses (DSA group: 26.0% and 43.6%, respectively; IMA group: 13.8% and 17.5%, respectively; p = 0.004). Both TKIs were well tolerated. Although the height standard deviation scores decreased in both groups, the height decline was greater in the DSA group between one and two years from the start of TKI therapy. In this study, dasatinib achieved faster and higher molecular responses with an acceptable safety profile. Further follow-up is necessary to assess the long-term outcomes of TKI treatment in children. Full article
(This article belongs to the Special Issue Inhibitors in Chronic Myeloid Leukemia)
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18 pages, 2528 KiB  
Systematic Review
Hematological Adverse Events with Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia: A Systematic Review with Meta-Analysis
by Olivia Kronick, Xinyu Chen, Nidhi Mehra, Armon Varmeziar, Rachel Fisher, David Kartchner, Vamsi Kota and Cassie S. Mitchell
Cancers 2023, 15(17), 4354; https://doi.org/10.3390/cancers15174354 - 31 Aug 2023
Cited by 2 | Viewed by 1322
Abstract
Chronic myeloid leukemia (CML) is treated with tyrosine kinase inhibitors (TKI) that target the pathological BCR-ABL1 fusion oncogene. The objective of this statistical meta-analysis was to assess the prevalence of other hematological adverse events (AEs) that occur during or after predominantly first-line treatment [...] Read more.
Chronic myeloid leukemia (CML) is treated with tyrosine kinase inhibitors (TKI) that target the pathological BCR-ABL1 fusion oncogene. The objective of this statistical meta-analysis was to assess the prevalence of other hematological adverse events (AEs) that occur during or after predominantly first-line treatment with TKIs. Data from seventy peer-reviewed, published studies were included in the analysis. Hematological AEs were assessed as a function of TKI drug type (dasatinib, imatinib, bosutinib, nilotinib) and CML phase (chronic, accelerated, blast). AE prevalence aggregated across all severities and phases was significantly different between each TKI (p < 0.05) for anemia—dasatinib (54.5%), bosutinib (44.0%), imatinib (32.8%), nilotinib (11.2%); neutropenia—dasatinib (51.2%), imatinib (29.8%), bosutinib (14.1%), nilotinib (14.1%); thrombocytopenia—dasatinib (62.2%), imatinib (30.4%), bosutinib (35.3%), nilotinib (22.3%). AE prevalence aggregated across all severities and TKIs was significantly (p < 0.05) different between CML phases for anemia—chronic (28.4%), accelerated (66.9%), blast (55.8%); neutropenia—chronic (26.7%), accelerated (63.8%), blast (36.4%); thrombocytopenia—chronic (33.3%), accelerated (65.6%), blast (37.9%). An odds ratio (OR) with 95% confidence interval was used to compare hematological AE prevalence of each TKI compared to the most common first-line TKI therapy, imatinib. For anemia, dasatinib OR = 1.65, [1.51, 1.83]; bosutinib OR = 1.34, [1.16, 1.54]; nilotinib OR = 0.34, [0.30, 0.39]. For neutropenia, dasatinib OR = 1.72, [1.53, 1.92]; bosutinib OR = 0.47, [0.38, 0.58]; nilotinib OR = 0.47, [0.42, 0.54]. For thrombocytopenia, dasatinib OR = 2.04, [1.82, 2.30]; bosutinib OR = 1.16, [0.97, 1.39]; nilotinib OR = 0.73, [0.65, 0.82]. Nilotinib had the greatest fraction of severe (grade 3/4) hematological AEs (30%). In conclusion, the overall prevalence of hematological AEs by TKI type was: dasatinib > bosutinib > imatinib > nilotinib. Study limitations include inability to normalize for dosage and treatment duration. Full article
(This article belongs to the Special Issue Inhibitors in Chronic Myeloid Leukemia)
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