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. 2022 May 27;12(6):881.
doi: 10.3390/jpm12060881.

Advanced Molecular Characterisation in Relapsed and Refractory Paediatric Acute Leukaemia, the Key for Personalised Medicine

Víctor Galán-Gómez  1   2 , Nerea Matamala  2 , Beatriz Ruz-Caracuel  2 , Paula Valle-Simón  3 , Bárbara Ochoa-Fernández  1 , Pilar Guerra-García  1 , Alicia Pernas-Sánchez  2 , Jordi Minguillón  2 , Berta González  1 , Isabel Martínez-Romera  1 , Sonsoles San Román-Pacheco  1 , Pablo Estival-Monteliú  4 , Adrián Ibáñez-Navarro  4 , Antonio Pérez-Martínez  1   4 , Adela Escudero-López  2
Affiliations

Advanced Molecular Characterisation in Relapsed and Refractory Paediatric Acute Leukaemia, the Key for Personalised Medicine

Víctor Galán-Gómez et al. J Pers Med. .

Abstract

Relapsed and refractory (R/r) disease in paediatric acute leukaemia remains the first reason for treatment failure. Advances in molecular characterisation can ameliorate the identification of genetic biomarkers treatment strategies for this disease, especially in high-risk patients. The purpose of this study was to analyse a cohort of R/r children diagnosed with acute lymphoblastic (ALL) or myeloid (AML) leukaemia in order to offer them a targeted treatment if available. Advanced molecular characterisation of 26 patients diagnosed with R/r disease was performed using NGS, MLPA, and RT-qPCR. The clinical relevance of the identified alterations was discussed in a multidisciplinary molecular tumour board (MTB). A total of 18 (69.2%) patients were diagnosed with B-ALL, 4 (15.4%) with T-ALL, 3 (11.5%) with AML and 1 patient (3.8%) with a mixed-phenotype acute leukaemia (MPL). Most of the patients had relapsed disease (88%) at the time of sample collection. A total of 17 patients (65.4%) were found to be carriers of a druggable molecular alteration, 8 of whom (47%) received targeted therapy, 7 (87.5%) of them in addition to hematopoietic stem cell transplantation (HSCT). Treatment response and disease control were achieved in 4 patients (50%). In conclusion, advanced molecular characterisation and MTB can improve treatment and outcome in paediatric R/r acute leukaemias.

Keywords: NGS; advanced molecular characterisation; genetics; paediatric acute leukaemia; personalised medicine; refractory; relapsed.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Work flow from sample collection to MTB recommendation.
Figure 2
Figure 2
Advanced molecular characterisation of the analysed samples.
See this image and copyright information in PMC

References

    1. Pui C.-H., Gajjar A.J., Kane J.R., Qaddoumi I.A., Pappo A.S. Challenging Issues in Pediatric Oncology. Nat. Rev. Clin. Oncol. 2011;8:540–549. doi: 10.1038/nrclinonc.2011.95. - DOI - PMC - PubMed
    1. Downing J.R., Wilson R.K., Zhang J., Mardis E.R., Pui C.-H., Ding L., Ley T.J., Evans W.E. The Pediatric Cancer Genome Project. Nat. Genet. 2012;44:619–622. doi: 10.1038/ng.2287. - DOI - PMC - PubMed
    1. Onciu M., Pui C.-H. Diagnosis and Classification. In: Pui C.-H., editor. Childhood Leukemias. Cambridge University Press; Cambridge, UK: 2012. pp. 21–48.
    1. Inaba H., Mullighan C.G. Pediatric Acute Lymphoblastic Leukemia. Haematology. 2020;105:2524–2539. doi: 10.3324/haematol.2020.247031. - DOI - PMC - PubMed
    1. de Morais R.V., de Souza M.V., de Silva K.A.S., Santiago P., Lorenzoni M.C., Lorea C.F., de Junior C.G.C., Taniguchi A.N.R., Scherer F.F., Michalowski M.B., et al. Epidemiological Evaluation and Survival of Children with Acute Myeloid Leukemia. J. Pediatr. 2021;97:204–210. doi: 10.1016/j.jped.2020.02.003. - DOI - PMC - PubMed

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