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Precision medicine in acute lymphoblastic leukemia

The cure rate of childhood acute lymphoblastic leukemia (ALL) has exceeded 90% in some contemporary clinical trials. However, the dose intensity of conventional chemotherapy has been pushed to its limit. Further improvement in outcome will need to rely more heavily on molecular therapeutic as well a...

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Autor principal: Pui, Ching-Hon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671279/
https://www.ncbi.nlm.nih.gov/pubmed/33074527
http://dx.doi.org/10.1007/s11684-020-0759-8
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author Pui, Ching-Hon
author_facet Pui, Ching-Hon
author_sort Pui, Ching-Hon
collection PubMed
description The cure rate of childhood acute lymphoblastic leukemia (ALL) has exceeded 90% in some contemporary clinical trials. However, the dose intensity of conventional chemotherapy has been pushed to its limit. Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immunoand cellular-therapy approaches together with precise risk stratification. Children with ETV6-RUNX1 or hyperdiploid > 50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment. Patients with Philadelphia chromosome (Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib. BH3 profiling and other preclinical methods have identified several high-risk subtypes, such as hypodiplod, early T-cell precursor, immature T-cell, KMT2A-rearranged, Ph-positive and TCF-HLF-positive ALL, that may respond to BCL-2 inhibitor venetoclax. There are other fusions or mutations that may serve as putative targets, but effective targeted therapy has yet to be established. For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions, current approaches that offer hope include blinatumomab, inotuzumab and CAR-T cell therapy for B-ALL, and daratumumab and nelarabine for T-ALL. With the expanding therapeutic armamentarium, we should start focus on rational combinations of targeted therapy with non-overlapping toxicities.
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spelling pubmed-96712792022-11-17 Precision medicine in acute lymphoblastic leukemia Pui, Ching-Hon Front Med Article The cure rate of childhood acute lymphoblastic leukemia (ALL) has exceeded 90% in some contemporary clinical trials. However, the dose intensity of conventional chemotherapy has been pushed to its limit. Further improvement in outcome will need to rely more heavily on molecular therapeutic as well as immunoand cellular-therapy approaches together with precise risk stratification. Children with ETV6-RUNX1 or hyperdiploid > 50 ALL who achieve negative minimal residual disease during early remission induction are suitable candidates for reduction in treatment. Patients with Philadelphia chromosome (Ph)-positive or Ph-like ALL with ABL-class fusion should be treated with dasatinib. BH3 profiling and other preclinical methods have identified several high-risk subtypes, such as hypodiplod, early T-cell precursor, immature T-cell, KMT2A-rearranged, Ph-positive and TCF-HLF-positive ALL, that may respond to BCL-2 inhibitor venetoclax. There are other fusions or mutations that may serve as putative targets, but effective targeted therapy has yet to be established. For other high-risk patients or poor early treatment responders who do not have targetable genetic lesions, current approaches that offer hope include blinatumomab, inotuzumab and CAR-T cell therapy for B-ALL, and daratumumab and nelarabine for T-ALL. With the expanding therapeutic armamentarium, we should start focus on rational combinations of targeted therapy with non-overlapping toxicities. 2020-12 2020-10-19 /pmc/articles/PMC9671279/ /pubmed/33074527 http://dx.doi.org/10.1007/s11684-020-0759-8 Text en https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Pui, Ching-Hon
Precision medicine in acute lymphoblastic leukemia
title Precision medicine in acute lymphoblastic leukemia
title_full Precision medicine in acute lymphoblastic leukemia
title_fullStr Precision medicine in acute lymphoblastic leukemia
title_full_unstemmed Precision medicine in acute lymphoblastic leukemia
title_short Precision medicine in acute lymphoblastic leukemia
title_sort precision medicine in acute lymphoblastic leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671279/
https://www.ncbi.nlm.nih.gov/pubmed/33074527
http://dx.doi.org/10.1007/s11684-020-0759-8
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