Publication:
Earlier relapse detection after allogeneic haematopoietic stem cell transplantation by chimerism assays: Digital PCR versus quantitative real-time PCR of insertion/deletion polymorphisms.

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Date

2019-02-22

Authors

Valero-Garcia, Jennifer
Gonzalez-Espinosa, Maria Del Carmen
Barrios, Manuel
Carmona-Antoñanzas, Greta
Garcia-Planells, Javier
Ruiz-Lafora, Carlos
Fuentes-Galvez, Ainhoa
Jimenez-Velasco, Antonio

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Public Library of Science
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Abstract

The analysis of molecular haematopoietic chimerisms (HC) has become a well-established method to monitor the transplant evolution and to assess the risk of relapse after allogeneic stem cells transplantation (allo-STC). Different techniques and molecular markers are being used for chimerism surveillance after transplantation, including quantitative real-time PCR (qPCR) and the recently developed digital PCR (dPCR). This study aims to compare the sensitivity and accuracy of both methods to quantify HC and predict early relapse. HC was evaluated using custom PCR systems for the specific detection of the Y-chromosome, null alleles and insertion-deletion polymorphisms. A total of 281 samples from 28 adult patients who underwent an allo-SCT were studied. Increasing mixed chimerism was detected prior to relapse in 100% of patients (18 relapses). Compared with conventional qPCR amplification, dPCR predicted relapse with a median anticipation period of 63 days versus 45.5 days by qPCR. Overall, 56% of the relapses were predicted earlier with dPCR whereas 38% of the relapses where detected simultaneously using both techniques and only in 1 case, relapse was predicted earlier with qPCR. In conclusion, chimerism determination by dPCR constitutes a suitable technique for the follow-up of patients with haematological pathologies after allo-STC, showing greater sensitivity to predict an early relapse.

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MeSH Terms

Adult
Female
Humans
Male
Middle Aged
Polymorphism, Genetic
Real-Time Polymerase Chain Reaction
Recurrence
Transplantation Chimera
Transplantation, Homologous

DeCS Terms

Recurrencia
Quimerismo
Trasplante
Sensibilidad y Especificidad
Reacción en Cadena de la Polimerasa
Células Madre
Vigilancia en Desastres

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Keywords

Hematologic Neoplasms, Hematopoietic Stem Cell Transplantation, INDEL Mutation

Citation

Valero-Garcia J, González-Espinosa MDC, Barrios M, Carmona-Antoñanzas G, García-Planells J, Ruiz-Lafora C, et al. Earlier relapse detection after allogeneic haematopoietic stem cell transplantation by chimerism assays: Digital PCR versus quantitative real-time PCR of insertion/deletion polymorphisms. PLoS One. 2019 Feb 22;14(2):e0212708. doi: 10.1371/journal.pone.0212708. Erratum in: PLoS One. 2019 Mar 13;14(3):e0213966