Journal
BLOOD
Volume 118, Issue 8, Pages 2077-2084Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-03-338707
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Funding
- Comitato M.L. Verga
- Fondazione Tettamanti (Monza)
- Fondazione Citta della Speranza
- Fondazione Cariparo (Padova)
- Associazione Gian Franco Lupo (Pomarico)
- Associazione Italiana per la Ricerca sul Cancro [mgv IG 5017]
- Fondazione Cariplo
- Ministero dell'Istruzione, Universita e Ricerca (MIUR)
- Deutsche Krebshilfe, Bonn, Germany [50-2698 Schr1, 50-2410 Ba7]
- Federal Ministry of Research, Oncosuisse/Krebsforschung Schweiz [OCS 1230-02-2002]
- St Anna Kinderkrebsforschung Austria
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The prognostic value of MRD in large series of childhood T-ALL has not yet been established. Trial AIEOP-BFM-ALL 2000 introduced standardized quantitative assessment of MRD for stratification, based on immunoglobulin and TCR gene rearrangements as polymerase chain reaction targets: Patients were considered MRD standard risk (MRD-SR) if MRD was negative at day 33 (time point 1 [TP1]) and day 78 (TP2), analyzed by at least 2 sensitive markers; MRD intermediate risk (MRD-IR) if positive either at day 33 or 78 and < 10(-3) at day 78; and MRD high risk (MRD-HR) if >= 10(-3) at day 78. A total of 464 patients with T-ALL were stratified by MRD: 16% of them were MRD-SR, 63% MRD-IR, and 21% MRD-HR. Their 7-year event-free-survival (SE) was 91.1% (3.5%), 80.6% (2.3%), and 49.8% (5.1%) (P < .001), respectively. Negativity of MRD at TP1 was the most favorable prognostic factor. An excellent outcome was also obtained in 32% of patients turning MRD negative only at TP2, indicating that early (TP1) MRD levels were irrelevant if MRD at TP2 was negative (48% of all patients). MRD >= 10(-3) at TP2 constitutes the most important predictive factor for relapse in childhood T-ALL. The study is registered at http://www.clinicaltrials.gov; Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With Acute Lymphoblastic Leukemia, protocol identification #NCT00430118 for BFM and #NCT00613457 for AIEOP. (Blood. 2011;118(8):2077-2084)
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