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Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa

BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that harbors the Philadelphia chromosome. Tyrosine kinase inhibitor (TKI) therapy has dramatically improved the survival of patients with CML. Nevertheless, 20%–40% of CML patients require changes in TKI therapy due to intol...

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Autores principales: Benjamin, Caryn, Murugan, Stephanie, Hoosen, Siddeeq, Rapiti, Nadine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313909/
https://www.ncbi.nlm.nih.gov/pubmed/37396560
http://dx.doi.org/10.1002/hsr2.1376
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author Benjamin, Caryn
Murugan, Stephanie
Hoosen, Siddeeq
Rapiti, Nadine
author_facet Benjamin, Caryn
Murugan, Stephanie
Hoosen, Siddeeq
Rapiti, Nadine
author_sort Benjamin, Caryn
collection PubMed
description BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that harbors the Philadelphia chromosome. Tyrosine kinase inhibitor (TKI) therapy has dramatically improved the survival of patients with CML. Nevertheless, 20%–40% of CML patients require changes in TKI therapy due to intolerance or drug resistance. A total of 30%–60% of resistant cases result from kinase domain (KD) mutations. There is currently no published data on CML KD mutations in South Africa. METHODS: This retrospective, descriptive study collected data from 206 CML patients attending the King Edward Hospital Hematology clinic. Patient‐based and mutation‐based factors were analyzed using descriptive statistical analysis and Kaplan–Meier curves for survival analysis. RESULTS: KD mutations were detected in 29.1% (n = 60 of 206). A total of 40 different KD mutations were detected, with unknown responses to TKI therapy in 65% (n = 26 of 40). A total of 57.7% (n = 15 of 26) of mutations with an unknown response, showed a response to specific TKIs in our study. Four patients had A399T mutations, of which two showed good responses to Nilotinib. Patients with I293N and V280M mutations showed good responses to Imatinib. G250E was most frequently detected. Despite M351T being one of six most commonly reported KD mutations globally, this mutation was not detected in our patient cohort. A total of 20.9% (n = 43 of 206) human immunodeficiency virus (HIV) positive patients were identified, of which 25.6% (n = 11 of 43) had KD mutations. HIV status showed no significant effect on mutational status or overall survival. CONCLUSION: The predicted response to TKI therapy was unknown in more than half of the KD mutations detected in our patient population. Additionally, eight patients with mutations with known responses to TKIs showed responses discordant to that expected. HIV status and KD mutations had no statistically significant effect on overall survival. Although some data were comparable to international publications, few notable differences warrant further investigation.
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spelling pubmed-103139092023-07-02 Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa Benjamin, Caryn Murugan, Stephanie Hoosen, Siddeeq Rapiti, Nadine Health Sci Rep Original Research BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that harbors the Philadelphia chromosome. Tyrosine kinase inhibitor (TKI) therapy has dramatically improved the survival of patients with CML. Nevertheless, 20%–40% of CML patients require changes in TKI therapy due to intolerance or drug resistance. A total of 30%–60% of resistant cases result from kinase domain (KD) mutations. There is currently no published data on CML KD mutations in South Africa. METHODS: This retrospective, descriptive study collected data from 206 CML patients attending the King Edward Hospital Hematology clinic. Patient‐based and mutation‐based factors were analyzed using descriptive statistical analysis and Kaplan–Meier curves for survival analysis. RESULTS: KD mutations were detected in 29.1% (n = 60 of 206). A total of 40 different KD mutations were detected, with unknown responses to TKI therapy in 65% (n = 26 of 40). A total of 57.7% (n = 15 of 26) of mutations with an unknown response, showed a response to specific TKIs in our study. Four patients had A399T mutations, of which two showed good responses to Nilotinib. Patients with I293N and V280M mutations showed good responses to Imatinib. G250E was most frequently detected. Despite M351T being one of six most commonly reported KD mutations globally, this mutation was not detected in our patient cohort. A total of 20.9% (n = 43 of 206) human immunodeficiency virus (HIV) positive patients were identified, of which 25.6% (n = 11 of 43) had KD mutations. HIV status showed no significant effect on mutational status or overall survival. CONCLUSION: The predicted response to TKI therapy was unknown in more than half of the KD mutations detected in our patient population. Additionally, eight patients with mutations with known responses to TKIs showed responses discordant to that expected. HIV status and KD mutations had no statistically significant effect on overall survival. Although some data were comparable to international publications, few notable differences warrant further investigation. John Wiley and Sons Inc. 2023-06-30 /pmc/articles/PMC10313909/ /pubmed/37396560 http://dx.doi.org/10.1002/hsr2.1376 Text en © 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Research
Benjamin, Caryn
Murugan, Stephanie
Hoosen, Siddeeq
Rapiti, Nadine
Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa
title Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa
title_full Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa
title_fullStr Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa
title_full_unstemmed Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa
title_short Chronic myeloid leukemia kinase domain mutations: A retrospective descriptive study on the therapeutic and prognostic significance in patients at King Edward VIII Hospital, KwaZulu‐Natal, South Africa
title_sort chronic myeloid leukemia kinase domain mutations: a retrospective descriptive study on the therapeutic and prognostic significance in patients at king edward viii hospital, kwazulu‐natal, south africa
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10313909/
https://www.ncbi.nlm.nih.gov/pubmed/37396560
http://dx.doi.org/10.1002/hsr2.1376
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