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Ann Hematol. 2017 Jul;96(7):1069-1075. doi: 10.1007/s00277-017-3002-1. Epub 2017 Apr 27.

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.

Author information

1
Instituto de Investigación Hospital 12 de Octubre (i+12), Servicio de Hematología, Hematología Traslacional, Hospital Universitario 12 de Octubre, Avda de Andalucía s/n, 28041, Madrid, Spain.
2
Institut de Recerca contra la Leucèmia Josep Carreras, ICO-Hospital Germans Trias i Pujol, Badalona, Spain.
3
ICO-Hospital Duran i Reynals (Bellvitge), Barcelona, Spain.
4
Hospital Universitari i Politècnic La Fe, Valencia, Spain.
5
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
6
Hospital Universitari Vall d'Hebron, Barcelona, Spain.
7
Hospital Universitario Virgen del Rocío, Sevilla, Spain.
8
Hospital Regional Universitario Carlos Haya, Málaga, Spain.
9
Hospital Universitario Lucus Augusti, Lugo, Spain.
10
Hospital General Universitario de Alicante, Alicante, Spain.
11
Hospital Universitario Central de Asturias, Oviedo, Spain.
12
Hospital Universitari Joan XXIII, Tarragona, Spain.
13
Hospital del Mar, Barcelona, Spain.
14
Hospital General Universitario Morales Meseguer, Murcia, Spain.
15
Hospital Universitario Virgen de la Victoria, Málaga, Spain.
16
Hospital de Fuenlabrada, Fuenlabrada, Madrid, Spain.
17
ICO-Hospital Universitari Dr. Josep Trueta, Girona, Spain.
18
Hospital Universitario de Salamanca, Salamanca, Spain.
19
Hospital Universitari Arnau de Vilanova, Lleida, Spain.
20
Hospital Universitari Parc Taulí, Sabadell, Barcelona, Spain.
21
Instituto de Investigación Hospital 12 de Octubre (i+12), Servicio de Hematología, Hematología Traslacional, Hospital Universitario 12 de Octubre, Avda de Andalucía s/n, 28041, Madrid, Spain. jmarti01@med.ucm.es.

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.

KEYWORDS:

Acute lymphoblastic leukemia relapse; BCR-ABL1; Central nervous system; Mutation analysis; Neoplasia

PMID:
28451802
PMCID:
PMC5486784
DOI:
10.1007/s00277-017-3002-1
[Indexed for MEDLINE]
Free PMC Article

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