Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid

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• dc.contributor.author Sánchez, Ricardo Juanca
• dc.contributor.author Abella Monreal, Eugeniaca
• dc.contributor.author Martínez-López, Joaquínca
• dc.date.accessioned 2018-03-22T08:39:55Z
• dc.date.available 2018-03-22T08:39:55Z
• dc.date.issued 2017
• dc.description.abstract We investigated the frequency, predictors, and evolution of acute lymphoblastic leukemia (ALL) in patients with CNS relapse and introduced a novel method for studying BCR-ABL1 protein variants in cDNA from bone marrow (BM) and cerebrospinal fluid (CSF) blast cells. A total of 128 patients were analyzed in two PETHEMA clinical trials. All achieved complete remission after imatinib treatment. Of these, 30 (23%) experienced a relapse after achieving complete remission, and 13 (10%) had an isolated CNS relapse or combined CNS and BM relapses. We compared the characteristics of patients with and without CNS relapse and further analyzed CSF and BM samples from two of the 13 patients with CNS relapse. In both patients, classical sequencing analysis of the kinase domain of BCR-ABL1 from the cDNA of CSF blasts revealed the pathogenic variant p.L387M. We also performed ultra-deep next-generation sequencing (NGS) in three samples from one of the relapsed patients. We did not find the mutation in the BM sample, but we did find it in CSF blasts with 45% of reads at the time of relapse. These data demonstrate the feasibility of detecting BCR-ABL1 mutations in CSF blasts by NGS and highlight the importance of monitoring clonal evolution over time.
• dc.format.mimetype application/pdf
• dc.identifier.citation Sanchez R, Ayala R, Alonso RA, Martínez MP, Ribera J, García O. et al. Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluid. Ann Hematol. 2017 Jul;96(7):1069-1075. DOI: 10.1007/s00277-017-3002-1
• dc.identifier.doi http://dx.doi.org/10.1007/s00277-017-3002-1
• dc.identifier.issn 0939-5555
• dc.identifier.uri http://hdl.handle.net/10230/34233
• dc.language.iso eng
• dc.publisher Springerca
• dc.relation.ispartof Annals of Hematology. 2017 Jul;96(7):1069-75
• dc.rights Copyright © The Author(s) 2017 . Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Acute lymphoblastic leukemia relapse
• dc.subject.keyword BCR-ABL1
• dc.subject.keyword Central nervous system
• dc.subject.keyword Mutation analysis
• dc.subject.keyword Neoplasia
• dc.subject.other Sistema nerviós central
• dc.subject.other Leucèmia limfoblàstica
• dc.title Clinical characteristics of patients with central nervous system relapse in BCR-ABL1-positive acute lymphoblastic leukemia: the importance of characterizing ABL1 mutations in cerebrospinal fluidca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion