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

نویسندگان

  • Martin Schrappe
  • Maria Grazia Valsecchi
  • Claus R Bartram
  • André Schrauder
  • Renate Panzer-Grümayer
  • Anja Möricke
  • Rosanna Parasole
  • Martin Zimmermann
  • Michael Dworzak
  • Barbara Buldini
  • Alfred Reiter
  • Giuseppe Basso
  • Thomas Klingebiel
  • Chiara Messina
  • Richard Ratei
  • Giovanni Cazzaniga
  • Rolf Koehler
  • Franco Locatelli
  • Beat W Schäfer
  • Maurizio Aricò
  • Karl Welte
  • Jacques J M van Dongen
  • Helmut Gadner
  • Andrea Biondi
  • Valentino Conter
چکیده

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.

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عنوان ژورنال:
  • Blood

دوره 118 8  شماره 

صفحات  -

تاریخ انتشار 2011