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

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 surveill...

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Bibliographic Details
Published in:PloS one 2019-02, Vol.14 (2), p.e0212708-e0212708
Main Authors: Valero-Garcia, Jennifer, González-Espinosa, María Del Carmen, Barrios, Manuel, Carmona-Antoñanzas, Greta, García-Planells, Javier, Ruiz-Lafora, Carlos, Fuentes-Gálvez, Ainhoa, Jiménez-Velasco, Antonio
Format: Article
Language:English
Subjects:
Accuracy
Adult
Alleles
Analysis
Biology and Life Sciences
Bone marrow
Chimerism
Chromosome deletion
Clonal deletion
Disease
EDTA
Female
Genetic aspects
Hematologic Neoplasms - genetics
Hematologic Neoplasms - therapy
Hematology
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cells
Hospitals
Humans
INDEL Mutation
Insertion
Intelligence gathering
Leukemia
Male
Medical research
Medicine and Health Sciences
Methods
Middle Aged
Mutation
Patients
Polymerase chain reaction
Polymorphism, Genetic
Real time
Real-Time Polymerase Chain Reaction
Recurrence
Recurrence (Disease)
Research and Analysis Methods
Sensitivity
Stem cell transplantation
Stem cells
Surveillance
Transplantation
Transplantation Chimera - genetics
Transplantation, Homologous
Transplants & implants
Y chromosomes
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0212708