Improving the Identification of High Risk Precursor B Acute Lymphoblastic Leukemia Patients with Earlier Quantification of Minimal Residual Disease

被引:14
|
作者
Karsa, Mawar [1 ]
Dalla Pozza, Luciano [2 ]
Venn, Nicola C. [1 ]
Law, Tamara [1 ]
Shi, Rachael [1 ]
Giles, Jodie E. [1 ]
Bahar, Anita Y. [1 ]
Cross, Shamira [2 ]
Catchpoole, Daniel [2 ]
Haber, Michelle [1 ]
Marshall, Glenn M. [1 ,3 ]
Norris, Murray D. [1 ]
Sutton, Rosemary [1 ]
机构
[1] Univ NSW, Lowy Canc Res Ctr, Childrens Canc Inst Australia Med Res, Sydney, NSW, Australia
[2] Childrens Hosp Westmead, Oncol Unit, Westmead, NSW, Australia
[3] Sydneys Childrens Hosp, Ctr Childrens Canc & Blood Disorders, Randwick, NSW, Australia
来源
PLOS ONE | 2013年 / 8卷 / 10期
基金
英国医学研究理事会;
关键词
AIEOP-BFM; T-CELL; GENE REARRANGEMENTS; MOLECULAR RESPONSE; FLOW-CYTOMETRY; THERAPY; IMMUNOGLOBULIN; CHILDREN;
D O I
10.1371/journal.pone.0076455
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (>= 1x10(-2)) and day 33 (>= 5x1(-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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页数:6
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