Improving the identification of high risk precursor B acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease.

The stratification of patients with acute lymphoblastic leukemia (ALL) into treatment risk groups based on quantification of minimal residual disease (MRD) after induction therapy is now well accepted but the relapse rate of about 20% in intermediate risk patients remains a challenge. The purpose of...

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Main Authors: Mawar Karsa, Luciano Dalla Pozza, Nicola C Venn, Tamara Law, Rachael Shi, Jodie E Giles, Anita Y Bahar, Shamira Cross, Daniel Catchpoole, Michelle Haber, Glenn M Marshall, Murray D Norris, Rosemary Sutton
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3795712?pdf=render
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author Mawar Karsa
Luciano Dalla Pozza
Nicola C Venn
Tamara Law
Rachael Shi
Jodie E Giles
Anita Y Bahar
Shamira Cross
Daniel Catchpoole
Michelle Haber
Glenn M Marshall
Murray D Norris
Rosemary Sutton
author_facet Mawar Karsa
Luciano Dalla Pozza
Nicola C Venn
Tamara Law
Rachael Shi
Jodie E Giles
Anita Y Bahar
Shamira Cross
Daniel Catchpoole
Michelle Haber
Glenn M Marshall
Murray D Norris
Rosemary Sutton
author_sort Mawar Karsa
collection DOAJ
description The stratification of patients with acute lymphoblastic leukemia (ALL) into treatment risk groups based on quantification of minimal residual disease (MRD) after induction therapy is now well accepted but the relapse rate of about 20% in intermediate risk patients remains a challenge. The purpose of this study was to further improve stratification by MRD measurement at an earlier stage. MRD was measured in stored day 15 bone marrow samples for pediatric patients enrolled on ANZCHOG ALL8 using Real-time Quantitative PCR to detect immunoglobulin and T-cell receptor gene rearrangements with the same assays used at day 33 and day 79 in the original MRD stratification. MRD levels in bone marrow at day 15 and 33 were highly predictive of outcome in 223 precursor B-ALL patients (log rank Mantel-Cox tests both P<0.001) and identified patients with poor, intermediate and very good outcomes. The combined use of MRD at day 15 (≥ 1 × 10(-2)) and day 33 (≥ 5 × 1(-5)) identified a subgroup of medium risk precursor B-ALL patients as poor MRD responders with 5 year relapse-free survival of 55% compared to 84% for other medium risk patients (log rank Mantel-Cox test, P = 0.0005). Risk stratification of precursor B-ALL but not T-ALL could be improved by using MRD measurement at day 15 and day 33 instead of day 33 and day 79 in similar BFM-based protocols for children with this disease.
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spelling doaj.art-ff6710a95a2a4e4babfeda463f513f7a2022-12-21T17:26:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7645510.1371/journal.pone.0076455Improving the identification of high risk precursor B acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease.Mawar KarsaLuciano Dalla PozzaNicola C VennTamara LawRachael ShiJodie E GilesAnita Y BaharShamira CrossDaniel CatchpooleMichelle HaberGlenn M MarshallMurray D NorrisRosemary SuttonThe stratification of patients with acute lymphoblastic leukemia (ALL) into treatment risk groups based on quantification of minimal residual disease (MRD) after induction therapy is now well accepted but the relapse rate of about 20% in intermediate risk patients remains a challenge. The purpose of this study was to further improve stratification by MRD measurement at an earlier stage. MRD was measured in stored day 15 bone marrow samples for pediatric patients enrolled on ANZCHOG ALL8 using Real-time Quantitative PCR to detect immunoglobulin and T-cell receptor gene rearrangements with the same assays used at day 33 and day 79 in the original MRD stratification. MRD levels in bone marrow at day 15 and 33 were highly predictive of outcome in 223 precursor B-ALL patients (log rank Mantel-Cox tests both P<0.001) and identified patients with poor, intermediate and very good outcomes. The combined use of MRD at day 15 (≥ 1 × 10(-2)) and day 33 (≥ 5 × 1(-5)) identified a subgroup of medium risk precursor B-ALL patients as poor MRD responders with 5 year relapse-free survival of 55% compared to 84% for other medium risk patients (log rank Mantel-Cox test, P = 0.0005). Risk stratification of precursor B-ALL but not T-ALL could be improved by using MRD measurement at day 15 and day 33 instead of day 33 and day 79 in similar BFM-based protocols for children with this disease.http://europepmc.org/articles/PMC3795712?pdf=render
spellingShingle Mawar Karsa
Luciano Dalla Pozza
Nicola C Venn
Tamara Law
Rachael Shi
Jodie E Giles
Anita Y Bahar
Shamira Cross
Daniel Catchpoole
Michelle Haber
Glenn M Marshall
Murray D Norris
Rosemary Sutton
Improving the identification of high risk precursor B acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease.
PLoS ONE
title Improving the identification of high risk precursor B acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease.
title_full Improving the identification of high risk precursor B acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease.
title_fullStr Improving the identification of high risk precursor B acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease.
title_full_unstemmed Improving the identification of high risk precursor B acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease.
title_short Improving the identification of high risk precursor B acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease.
title_sort improving the identification of high risk precursor b acute lymphoblastic leukemia patients with earlier quantification of minimal residual disease
url http://europepmc.org/articles/PMC3795712?pdf=render
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