Publication:
Assessment of minimal residual disease by next generation sequencing in peripheral blood as a complementary tool for personalized transplant monitoring in myeloid neoplasms

Date

2020

Authors

Aguirre-Ruiz, Paula
Ariceta, Beñat
Viguria Alegría, María Cruz
Zudaire, María Teresa
Blasco-Iturri, Zuriñe
Arnedo, Patricia
Aguilera-Diaz, Almudena
Jauregui, Axier
Mañú, Amagoia
Prósper, Felipe

Director

Publisher

MDPI
Acceso abierto / Sarbide irekia
Artículo / Artikulua
Versión publicada / Argitaratu den bertsioa

Project identifier

MINECO//PI16%2F02024/ES/recolecta
ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016 (ISCIII)/PI17%2F00701/ES/recolecta
ISCIII/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020 (ISCIII)/PI19%2F01352/ES/recolecta
MINECO//CB16%2F12%2F00489/ES/recolecta
Gobierno de Navarra//0011-1411-2017-000028
Gobierno de Navarra//40%2F2016
Métricas Alternativas

Abstract

Patients with myeloid neoplasms who relapsed after allogenic hematopoietic stem cell transplant (HSCT) have poor prognosis. Monitoring of chimerism and specific molecular markers as a surrogate measure of relapse is not always helpful; therefore, improved systems to detect early relapse are needed. We hypothesized that the use of next generation sequencing (NGS) could be a suitable approach for personalized follow-up post-HSCT. To validate our hypothesis, we analyzed by NGS, a retrospective set of peripheral blood (PB) DNA samples previously evaluated by high-sensitive quantitative PCR analysis using insertion/deletion polymorphisms (indel-qPCR) chimerism engraftment. Post-HCST allelic burdens assessed by NGS and chimerism status showed a similar time-course pattern. At time of clinical relapse in 8/12 patients, we detected positive NGS-based minimal residual disease (NGS-MRD). Importantly, in 6/8 patients, we were able to detect NGS-MRD at time points collected prior to clinical relapse. We also confirmed the disappearance of post-HCST allelic burden in non-relapsed patients, indicating true clinical specificity. This study highlights the clinical utility of NGS-based post-HCST monitoring in myeloid neoplasia as a complementary specific analysis to high-sensitive engraftment testing. Overall, NGS-MRD testing in PB is widely applicable for the evaluation of patients following HSCT and highly valuable to personalized early treatment intervention when mixed chimerism is detected.

Description

Keywords

Next generation sequencing (NGS), Chimerism, Myeloid leukemia, Hematopoietic stem cell transplant (HSCT), Minimal residual disease (MRD)

Department

Ciencias de la Salud / Osasun Zientziak

Faculty/School

Degree

Doctorate program

item.page.cita

Aguirre-Ruiz, P., Ariceta, B., Viguria, M. C., Zudaire, M. T., Blasco-Iturri, Z., Arnedo, P., Aguilera-Diaz, A., Jauregui, A., Mañú, A., Prosper, F., Mateos, M. C., Fernández-Mercado, M., Larráyoz, M. J., Redondo, M., Calasanz, M. J., Vázquez, I., Bandrés, E. (2020). Assessment of minimal residual disease by next generation sequencing in peripheral blood as a complementary tool for personalized transplant monitoring in myeloid neoplasms. Journal of Clinical Medicine, 9(12), 1-20. https://doi.org/10.3390/jcm9123818.

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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

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