JavaScript is NOT enabled !

Please enable JavaScript.

Article

PubMed

This record comes from PubMed

Next-generation sequencing indicates false-positive MRD results and better predicts prognosis after SCT in patients with childhood ALL

Kotrova, M
Author Kotrova, M CLIP Laboratory Centre, Department of Pediatric Hematology/Oncology, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
van der Velden, V H J
Author van der Velden, V H J Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
van Dongen, J J M
Author van Dongen, J J M Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
Formankova, R
Author Formankova, R Department of Pediatric Hematology/Oncology, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
Sedlacek, P
Author Sedlacek, P Department of Pediatric Hematology/Oncology, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
Brüggemann, M
Author Brüggemann, M Department of Hematology, University Hospital Schleswig-Holstein, Kiel, Germany
Zuna, J
Author Zuna, J CLIP Laboratory Centre, Department of Pediatric Hematology/Oncology, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
Stary, J
Author Stary, J Department of Pediatric Hematology/Oncology, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
Trka, J
Author Trka, J CLIP Laboratory Centre, Department of Pediatric Hematology/Oncology, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
Fronkova, E
Author Fronkova, E CLIP Laboratory Centre, Department of Pediatric Hematology/Oncology, 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic

Bone marrow transplantation. 2017 Jul ; 52 (7) : 962-968. [epub] 20170227

Bone Marrow Transplant
ISSN 1476-5365 | 0268-3369
Source

Language English Country Great Britain, England Media print-electronic

Document type Clinical Trial, Journal Article, Multicenter Study

Persistent link https://www.medvik.cz/link/pmid28244980

PubMed 28244980
DOI 10.1038/bmt.2017.16
PII: bmt201716
Knihovny.cz E-resources

MeSH
Precursor Cell Lymphoblastic Leukemia-Lymphoma * blood diagnosis genetics therapy MeSH
Child MeSH
False Positive Reactions MeSH
Humans MeSH
Adolescent MeSH
Polymerase Chain Reaction * MeSH
Child, Preschool MeSH
Prognosis MeSH
Neoplasm, Residual MeSH
Hematopoietic Stem Cell Transplantation * MeSH
High-Throughput Nucleotide Sequencing * MeSH
Check Tag
Child MeSH
Humans MeSH
Adolescent MeSH
Male MeSH
Child, Preschool MeSH
Female MeSH
Publication type
Journal Article MeSH
Clinical Trial MeSH
Multicenter Study MeSH

Minimal residual disease (MRD) monitoring via quantitative PCR (qPCR) detection of Ag receptor gene rearrangements has been the most sensitive method for predicting prognosis and making post-transplant treatment decisions for patients with ALL. Despite the broad clinical usefulness and standardization of this method, we and others have repeatedly reported the possibility of false-positive MRD results caused by massive B-lymphocyte regeneration after stem cell transplantation (SCT). Next-generation sequencing (NGS) enables precise and sensitive detection of multiple Ag receptor rearrangements, thus providing a more specific readout compared to qPCR. We investigated two cohorts of children with ALL who underwent SCT (30 patients and 228 samples). The first cohort consisted of 17 patients who remained in long-term CR after SCT despite having low MRD positivity (<0.01%) at least once during post-SCT monitoring using qPCR. Only one of 27 qPCR-positive samples was confirmed to be positive by NGS. Conversely, 10 of 15 samples with low qPCR-detected MRD positivity from 13 patients who subsequently relapsed were also confirmed to be positive by NGS (P=0.002). These data show that NGS has a better specificity in post-SCT ALL management and indicate that treatment interventions aimed at reverting impending relapse should not be based on qPCR only.

CLIP Laboratory Centre Department of Pediatric Hematology Oncology 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Department of Hematology University Hospital Schleswig Holstein Kiel Germany

Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden The Netherlands

Department of Immunology Erasmus MC University Medical Center Rotterdam Rotterdam The Netherlands

Department of Pediatric Hematology Oncology 2nd Faculty of Medicine and University Hospital Motol Prague Czech Republic

Comment In

Bone Marrow Transplant. 2017 Jul;52(7):952-954. doi: 10.1038/bmt.2017.104. PubMed

See more in PubMed

Haematologica. 2007 May;92(5):612-8 PubMed

Leukemia. 1999 Jan;13(1):110-8 PubMed

Leukemia. 2010 Mar;24(3):521-35 PubMed

Bone Marrow Transplant. 2008 Aug;42(3):187-96 PubMed