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

M. Kotrova, VHJ. van der Velden, JJM. van Dongen, R. Formankova, P. Sedlacek, M. Brüggemann, J. Zuna, J. Stary, J. Trka, E. Fronkova,

. 2017 ; 52 (7) : 962-968. [pub] 20170227

Jazyk angličtina Země Velká Británie

Typ dokumentu klinické zkoušky, časopisecké články, multicentrická studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc18010777

Grantová podpora
NV16-32568A MZ0 CEP - Centrální evidence projektů

Digitální knihovna NLK
Plný text - Článek

E-zdroje Online Plný text

NLK Free Medical Journals od 1997 do Před 1 rokem
Freely Accessible Science Journals od 1997 do Před 1 rokem
ProQuest Central od 2000-01-01 do Před 1 rokem
Open Access Digital Library od 1997-01-01
Health & Medicine (ProQuest) od 2000-01-01 do Před 1 rokem

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.

Citace poskytuje Crossref.org

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