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Late MRD response determines relapse risk overall and in subsets of childhood T-cell ALL: results of the AIEOP-BFM-ALL 2000 study

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Zeitschriftentitel: Blood
Personen und Körperschaften: Schrappe, Martin, Valsecchi, Maria Grazia, Bartram, Claus R., Schrauder, André, Panzer-Grümayer, Renate, Möricke, Anja, Parasole, Rosanna, Zimmermann, Martin, Dworzak, Michael, Buldini, Barbara, Reiter, Alfred, Basso, Giuseppe, Klingebiel, Thomas, Messina, Chiara, Ratei, Richard, Cazzaniga, Giovanni, Koehler, Rolf, Locatelli, Franco, Schäfer, Beat W., Aricò, Maurizio, Welte, Karl, van Dongen, Jacques J.M., Gadner, Helmut, Biondi, Andrea, Conter, Valentino
In: Blood, 118, 2011, 8, S. 2077-2084
Format: E-Article
Sprache: Englisch
veröffentlicht:
American Society of Hematology
Schlagwörter:
Cell Biology
Hematology
Immunology
Biochemistry
Details
Zusammenfassung: <jats:title>Abstract</jats:title> <jats:p>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 &lt; 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 &lt; .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.</jats:p>
Umfang: 2077-2084
ISSN: 0006-4971
1528-0020
DOI: 10.1182/blood-2011-03-338707