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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...

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Autores principales: Shi, Ting, Wang, Huanping, Xie, Mixue, Li, Xueying, Zhu, Lixia, Ye, Xiujin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Faculdade de Medicina / USP 2020
Materias:
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.
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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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