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Prognostic significance of a normal karyotype in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era
OBJECTIVE: The occurrence of cryptic Philadelphia (Ph) chromosome translocation is rare in BCR-ABL1-positive acute lymphoblastic leukemia (BCR-ABL1(+) ALL) and is of unknown significance in the tyrosine kinase inhibitor (TKI) era. METHODS: We retrospectively studied a series of adult patients receiv...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Faculdade de Medicina / USP
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603291/ https://www.ncbi.nlm.nih.gov/pubmed/33206758 http://dx.doi.org/10.6061/clinics/2020/e2011 |
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author | Shi, Ting Wang, Huanping Xie, Mixue Li, Xueying Zhu, Lixia Ye, Xiujin |
author_facet | Shi, Ting Wang, Huanping Xie, Mixue Li, Xueying Zhu, Lixia Ye, Xiujin |
author_sort | Shi, Ting |
collection | PubMed |
description | OBJECTIVE: The occurrence of cryptic Philadelphia (Ph) chromosome translocation is rare in BCR-ABL1-positive acute lymphoblastic leukemia (BCR-ABL1(+) ALL) and is of unknown significance in the tyrosine kinase inhibitor (TKI) era. METHODS: We retrospectively studied a series of adult patients receiving TKI-based therapy to evaluate the prognostic impact of the normal karyotype (NK) (n=22) in BCR-ABL1(+) ALL by comparison with the isolated Ph(+) karyotype (n=54). RESULTS: There were no statistically significant differences in clinical characteristics and complete remission rate between the two groups. Compared with the isolated Ph(+) group, the NK/BCR-ABL1(+) group had a higher relapse rate (55.0% versus 29.4%, p=0.044). Overall survival (OS) and disease-free survival (DFS) were significantly shorter in the NK/BCR-ABL1(+) group than in the isolated Ph(+) group [median OS: 24.5 versus 48.6 (months), p=0.013; median DFS: 11.0 (months) versus undefined, p=0.008]. The five-year OS and DFS for patients with NK/BCR-ABL1(+) were 19.2% and 14.5%, respectively; those for patients with isolated Ph(+) were 49.5% and 55.7%, respectively. Thirty-four (44.7%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in this study. Among the patients who received allo-HSCT, the median OS and DFS in the NK/BCR-ABL(+) group (n=9) were 35.5 and 27.5 months, respectively, while those in the isolated Ph(+) group (n=25) were undefined. There was a trend of significant statistical difference in the OS between the two subgroups (p=0.066), but no significant difference in the DFS. Multivariate analysis revealed that NK was independently associated with worse OS and DFS in BCR-ABL1(+) ALL patients [Hazard ratio (HR) 2.256 (95% confidence interval (CI), 1.005-5.066), p=0.049; HR 2.711 (95% CI, 1.319-5.573), p=0.007]. CONCLUSION: Our results suggest that the sub-classification of an NK could be applied in the prognostic assessments of BCR-ABL1(+) ALL. In addition, allo-HSCT should be actively performed to improve prognosis in these patients. |
format | Online Article Text |
id | pubmed-7603291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Faculdade de Medicina / USP |
record_format | MEDLINE/PubMed |
spelling | pubmed-76032912020-11-10 Prognostic significance of a normal karyotype in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era Shi, Ting Wang, Huanping Xie, Mixue Li, Xueying Zhu, Lixia Ye, Xiujin Clinics (Sao Paulo) Original Article OBJECTIVE: The occurrence of cryptic Philadelphia (Ph) chromosome translocation is rare in BCR-ABL1-positive acute lymphoblastic leukemia (BCR-ABL1(+) ALL) and is of unknown significance in the tyrosine kinase inhibitor (TKI) era. METHODS: We retrospectively studied a series of adult patients receiving TKI-based therapy to evaluate the prognostic impact of the normal karyotype (NK) (n=22) in BCR-ABL1(+) ALL by comparison with the isolated Ph(+) karyotype (n=54). RESULTS: There were no statistically significant differences in clinical characteristics and complete remission rate between the two groups. Compared with the isolated Ph(+) group, the NK/BCR-ABL1(+) group had a higher relapse rate (55.0% versus 29.4%, p=0.044). Overall survival (OS) and disease-free survival (DFS) were significantly shorter in the NK/BCR-ABL1(+) group than in the isolated Ph(+) group [median OS: 24.5 versus 48.6 (months), p=0.013; median DFS: 11.0 (months) versus undefined, p=0.008]. The five-year OS and DFS for patients with NK/BCR-ABL1(+) were 19.2% and 14.5%, respectively; those for patients with isolated Ph(+) were 49.5% and 55.7%, respectively. Thirty-four (44.7%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in this study. Among the patients who received allo-HSCT, the median OS and DFS in the NK/BCR-ABL(+) group (n=9) were 35.5 and 27.5 months, respectively, while those in the isolated Ph(+) group (n=25) were undefined. There was a trend of significant statistical difference in the OS between the two subgroups (p=0.066), but no significant difference in the DFS. Multivariate analysis revealed that NK was independently associated with worse OS and DFS in BCR-ABL1(+) ALL patients [Hazard ratio (HR) 2.256 (95% confidence interval (CI), 1.005-5.066), p=0.049; HR 2.711 (95% CI, 1.319-5.573), p=0.007]. CONCLUSION: Our results suggest that the sub-classification of an NK could be applied in the prognostic assessments of BCR-ABL1(+) ALL. In addition, allo-HSCT should be actively performed to improve prognosis in these patients. Faculdade de Medicina / USP 2020-11-02 2020 /pmc/articles/PMC7603291/ /pubmed/33206758 http://dx.doi.org/10.6061/clinics/2020/e2011 Text en Copyright © 2020 CLINICS http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is properly cited. |
spellingShingle | Original Article Shi, Ting Wang, Huanping Xie, Mixue Li, Xueying Zhu, Lixia Ye, Xiujin Prognostic significance of a normal karyotype in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era |
title | Prognostic significance of a normal karyotype in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era |
title_full | Prognostic significance of a normal karyotype in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era |
title_fullStr | Prognostic significance of a normal karyotype in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era |
title_full_unstemmed | Prognostic significance of a normal karyotype in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era |
title_short | Prognostic significance of a normal karyotype in adult patients with BCR-ABL1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era |
title_sort | prognostic significance of a normal karyotype in adult patients with bcr-abl1-positive acute lymphoblastic leukemia in the tyrosine kinase inhibitor era |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603291/ https://www.ncbi.nlm.nih.gov/pubmed/33206758 http://dx.doi.org/10.6061/clinics/2020/e2011 |
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