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Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis

BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Although the prognostic value of BCR-ABL1 isoforms in Ph+ ALL patients has been investigated in numerous studies in the tyrosine kinase inhibitor (TKI) era, the results were still...

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Autores principales: Zhang, Wanhua, Kuang, Pu, Liu, Ting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748129/
https://www.ncbi.nlm.nih.gov/pubmed/33338050
http://dx.doi.org/10.1371/journal.pone.0243657
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author Zhang, Wanhua
Kuang, Pu
Liu, Ting
author_facet Zhang, Wanhua
Kuang, Pu
Liu, Ting
author_sort Zhang, Wanhua
collection PubMed
description BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Although the prognostic value of BCR-ABL1 isoforms in Ph+ ALL patients has been investigated in numerous studies in the tyrosine kinase inhibitor (TKI) era, the results were still conflicting. Hence we performed herein the meta-analysis to comprehensively assess the impact of BCR-ABL1 isoforms on the clinical outcomes of Ph+ ALL patients. Systematic literature review was conducted in PubMed, Embase, and Cochrane databases with the data access date up to June 15, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Furthermore, subgroup analyses were performed to assess the robustness of the associations. Nine studies with a total number of 1582 patients were eligible for this meta-analysis. Combined HRs suggested that p210 was slightly associated with inferior event-free survival (EFS) (HR = 1.34, 95% CI 1.05–1.72). The overall survival (OS) was not significantly affected (HR = 1.15, 95% CI 0.92–1.45). In subgroup analyses, the HRs showed a trend toward adverse impact of p210 on clinical outcomes. However, the confidence intervals were not crossing the null value only in a minority of subgroups including Caucasian studies, first-generation TKI treated cohort and transplant cohort. Our findings suggested that p210 might pose a mild adverse impact on the EFS of Ph+ ALL patients. This effect might be compromised by the use of second- or third-generation TKIs. Further studies are needed to verify our conclusions.
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spelling pubmed-77481292020-12-31 Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis Zhang, Wanhua Kuang, Pu Liu, Ting PLoS One Research Article BCR-ABL1 fusion gene is the driver mutation of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Although the prognostic value of BCR-ABL1 isoforms in Ph+ ALL patients has been investigated in numerous studies in the tyrosine kinase inhibitor (TKI) era, the results were still conflicting. Hence we performed herein the meta-analysis to comprehensively assess the impact of BCR-ABL1 isoforms on the clinical outcomes of Ph+ ALL patients. Systematic literature review was conducted in PubMed, Embase, and Cochrane databases with the data access date up to June 15, 2020. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Furthermore, subgroup analyses were performed to assess the robustness of the associations. Nine studies with a total number of 1582 patients were eligible for this meta-analysis. Combined HRs suggested that p210 was slightly associated with inferior event-free survival (EFS) (HR = 1.34, 95% CI 1.05–1.72). The overall survival (OS) was not significantly affected (HR = 1.15, 95% CI 0.92–1.45). In subgroup analyses, the HRs showed a trend toward adverse impact of p210 on clinical outcomes. However, the confidence intervals were not crossing the null value only in a minority of subgroups including Caucasian studies, first-generation TKI treated cohort and transplant cohort. Our findings suggested that p210 might pose a mild adverse impact on the EFS of Ph+ ALL patients. This effect might be compromised by the use of second- or third-generation TKIs. Further studies are needed to verify our conclusions. Public Library of Science 2020-12-18 /pmc/articles/PMC7748129/ /pubmed/33338050 http://dx.doi.org/10.1371/journal.pone.0243657 Text en © 2020 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Wanhua
Kuang, Pu
Liu, Ting
Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis
title Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis
title_full Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis
title_fullStr Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis
title_full_unstemmed Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis
title_short Role of BCR-ABL1 isoforms on the prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: A meta-analysis
title_sort role of bcr-abl1 isoforms on the prognosis of philadelphia chromosome positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era: a meta-analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748129/
https://www.ncbi.nlm.nih.gov/pubmed/33338050
http://dx.doi.org/10.1371/journal.pone.0243657
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