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
Por:
Sanchez, R, Ayala, R, Alonso, RA, Martinez, MP, Ribera, J, Garcia, O, Sanchez-Pina, J, Mercadal, S, Montesinos, P, Martino, R, Barba, P, Gonzalez-Campos, J, Barrios, M, Lavilla, E, Gil, C, Bernal, T, Escoda, L, Abella, E, Amigo, ML, Moreno, MJ, Bravo, P, Guardia, R, Hernandez-Rivas, JM, Garcia-Guinon, A, Piernas, S, Ribera, JM, Martinez-Lopez, J
Publicada:
1 jul 2017
Resumen:
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.
Filiaciones:
Sanchez, R:
Hosp Univ 12 Octubre, Inst Invest Hosp Octubre I 12 12, Serv Hematol, Hematol Traslac, Avda Andalucia S-N, Madrid 28041, Spain
Ayala, R:
Hosp Univ 12 Octubre, Inst Invest Hosp Octubre I 12 12, Serv Hematol, Hematol Traslac, Avda Andalucia S-N, Madrid 28041, Spain
Alonso, RA:
Hosp Univ 12 Octubre, Inst Invest Hosp Octubre I 12 12, Serv Hematol, Hematol Traslac, Avda Andalucia S-N, Madrid 28041, Spain
Martinez, MP:
Hosp Univ 12 Octubre, Inst Invest Hosp Octubre I 12 12, Serv Hematol, Hematol Traslac, Avda Andalucia S-N, Madrid 28041, Spain
Ribera, J:
ICO Hosp Germans Trias & Pujol, Inst Recerca Leucemia Josep Carreras, Badalona, Spain
Garcia, O:
ICO Hosp Germans Trias & Pujol, Inst Recerca Leucemia Josep Carreras, Badalona, Spain
Sanchez-Pina, J:
Hosp Univ 12 Octubre, Inst Invest Hosp Octubre I 12 12, Serv Hematol, Hematol Traslac, Avda Andalucia S-N, Madrid 28041, Spain
Mercadal, S:
ICO Hosp Duran & Reynals Bellvitge, Barcelona, Spain
Montesinos, P:
Hosp Univ & Politecn La Fe, Valencia, Spain
Martino, R:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Barba, P:
Hosp Univ Vall dHebron, Barcelona, Spain
Gonzalez-Campos, J:
Hosp Univ Virgen del Rocio, Seville, Spain
Barrios, M:
Hosp Reg Univ Carlos Haya, Malaga, Spain
Lavilla, E:
Hosp Univ Lucus Augusti, Lugo, Spain
Gil, C:
Hosp Gen Univ Alicante, Alicante, Spain
Bernal, T:
Hosp Univ Cent Asturias, Oviedo, Spain
Escoda, L:
Hosp Univ Joan XXIII, Tarragona, Spain
Abella, E:
Hosp del Mar, Barcelona, Spain
Amigo, ML:
Hosp Gen Univ Morales Meseguer, Murcia, Spain
Moreno, MJ:
Hosp Univ Virgen de la Victoria, Malaga, Spain
Bravo, P:
Hosp Fuenlabrada, Madrid, Spain
Guardia, R:
ICO Hosp Univ Dr Josep Trueta, Girona, Spain
Hernandez-Rivas, JM:
Hosp Univ Salamanca, Salamanca, Spain
Garcia-Guinon, A:
Hosp Arnau Vilanova, Lleida, Spain
Piernas, S:
Hosp Univ Parc Tauli, Barcelona, Spain
Ribera, JM:
ICO Hosp Germans Trias & Pujol, Inst Recerca Leucemia Josep Carreras, Badalona, Spain
Martinez-Lopez, J:
Hosp Univ 12 Octubre, Inst Invest Hosp Octubre I 12 12, Serv Hematol, Hematol Traslac, Avda Andalucia S-N, Madrid 28041, Spain
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