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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

  • Schrappe, Martin Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany;
  • Valsecchi, Maria Grazia Medical Statistics Unit, Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Monza, Italy;
  • Bartram, Claus R. Institute of Human Genetics, Ruprecht-Karls University, Heidelberg, Germany;
  • Schrauder, André Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany;
  • Panzer-Grümayer, Renate Children's Cancer Research Institute and St Anna Kinderspital, Wien, Austria;
  • Möricke, Anja Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany;
  • Parasole, Rosanna Department of Pediatrics Hemato-Oncology, Ospedale Pausillipon, Napoli, Italy;
  • Zimmermann, Martin Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany;
  • Dworzak, Michael Children's Cancer Research Institute and St Anna Kinderspital, Wien, Austria;
  • Buldini, Barbara Pediatric Hemato-Oncology, Department of Pediatrics “Salus Pueri,” University of Padova, Padova, Italy;
  • Reiter, Alfred Pediatric Hematology and Oncology, University Hospital Giessen, Giessen, Germany;
  • Basso, Giuseppe Pediatric Hemato-Oncology, Department of Pediatrics “Salus Pueri,” University of Padova, Padova, Italy;
  • Klingebiel, Thomas Pediatric Hematology and Oncology, University Hospital, Frankfurt, Germany;
  • Messina, Chiara Pediatric Hemato-Oncology, Department of Pediatrics “Salus Pueri,” University of Padova, Padova, Italy;
  • Ratei, Richard Hematology/Oncology, Robert-Rössle-Klinik at the HELIOS Klinikum, Charité, Berlin, Germany;
  • Cazzaniga, Giovanni Centro M. Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Monza, Italy;
  • Koehler, Rolf Institute of Human Genetics, Ruprecht-Karls University, Heidelberg, Germany;
  • Locatelli, Franco Department of Pediatric Hemato-Oncology, Ospedale Bambin Gesù, Rome, University of Pavia, Pavia, Italy;
  • Schäfer, Beat W. Pediatric Oncology, University Children's Hospital Zürich, Zürich, Switzerland;
  • Aricò, Maurizio Department of Pediatric Hematology Oncology, Azienda Ospedaliero-Universitaria Meyer, Firenze, Italy;
  • Welte, Karl Department of Pediatric Hematology and Oncology, Medical School Hannover, Hannover, Germany;
  • van Dongen, Jacques J.M. Department.of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands;
  • Gadner, Helmut Children's Cancer Research Institute and St Anna Kinderspital, Wien, Austria;
  • Biondi, Andrea Department of Pediatrics, University of Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy; and
  • Conter, Valentino Department of Pediatrics, Ospedali Riuniti, Bergamo, Italy
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  • Blood. - American Society of Hematology. - 2011, vol. 118, no. 8, p. 2077-2084
English Abstract
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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  • English
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green
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https://sonar.ch/global/documents/41742
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