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
Sanchez, R. (Hospital 12 de Octubre (Madrid))
Ayala, Rosa (Hospital 12 de Octubre (Madrid))
Alonso, R.A. (Hospital 12 de Octubre (Madrid))
Martínez, M.P. (Hospital 12 de Octubre (Madrid))
Ribera, Jordi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
García, Olga (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sanchez-Pina, J. (Hospital 12 de Octubre (Madrid))
Mercadal, S. (ICO-Hospital Duran i Reynals (Bellvitge))
Montesinos, P. (Hospital Universitari i Politècnic La Fe de València)
Martino Bofarull, Rodrigo (Institut d'Investigació Biomèdica Sant Pau)
Barba, Pere (Hospital Universitari Vall d'Hebron)
González-Campos, J. (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Barrios, M. (Hospital Regional Universitario Carlos Haya (Málaga))
Lavilla, E. (Hospital Universitario Lucus Augusti (Lugo))
Gil, C. (Hospital General Universitario de Alicante (Alacant, País Valencià))
Bernal, T. (Hospital Universitario Central de Asturias)
Escoda, Lourdes (Hospital Universitari Joan XXIII de Tarragona)
Abella Monreal, Eugenia (Hospital del Mar (Barcelona, Catalunya))
Amigo, María-Luz (Hospital General Universitario Morales Meseguer (Múrcia))
Moreno, M.J. (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Bravo, P. (Hospital de Fuenlabrada)
Guàrdia, R. (Hospital Universitari de Girona Doctor Josep Trueta)
Hernández-Rivas, J.M. (Hospital Universitario de Salamanca)
García-Guiñón, A. (Hospital Universitari Arnau de Vilanova)
Piernas, Sonia (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Ribera, José Maria (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martínez-López, J. (Hospital 12 de Octubre (Madrid))
Universitat Autònoma de Barcelona

Date:	2017
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.
Grants:	Instituto de Salud Carlos III RD12/0036/0061
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Acute lymphoblastic leukemia relapse ; BCR-ABL1 ; Central nervous system ; Mutation analysis ; Neoplasia
Published in:	Annals of Hematology, Vol. 96 Núm. 7 (january 2017) , p. 1069-1075, ISSN 1432-0584

DOI: 10.1007/s00277-017-3002-1
PMID: 28451802

7 p, 660.3 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles