Remission, treatment failure, and relapse in pediatric ALL: an international consensus of the Ponte-di-Legno Consortium

  • Swantje Buchmann
    Department of Pediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany;
  • Martin Schrappe
    Department of Pediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany;
  • Andre Baruchel
    Pediatric Hematology-Immunology Department, University Hospital Robert Debré Assistance Publique–Hôpitaux de Paris (AP-HP), Université de Paris, Paris;
  • Andrea Biondi
    Department of Pediatrics and Tettamanti Research Center, Fondazione MBBM (Monza e Brianza per il Bambino e la sua Mamma)/Ospedale San Gerardo, University of Milano-Bicocca, Monza, Italy;
  • Michael Borowitz
    Department of Pediatrics and Pediatric Surgery, Hospital de Niños Roberto del Río, Facultad de Medicina, Universidad de Chile, Santiago, Chile;
  • Myriam Campbell
    Chilean National Pediatric Oncology Group (PINDA), Santiago, Chile;
  • Gunnar Cario
    Department of Pediatrics, University Medical Center Schleswig-Holstein, Kiel, Germany;
  • Giovanni Cazzaniga
    Department of Pediatrics and Tettamanti Research Center, Fondazione MBBM (Monza e Brianza per il Bambino e la sua Mamma)/Ospedale San Gerardo, University of Milano-Bicocca, Monza, Italy;
  • Gabriele Escherich
    Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;
  • Christine J. Harrison
    Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle-upon-Tyne, United Kingdom;
  • Mats Heyman
    Childhood Cancer Research Unit, Karolinska Institutet–Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden;
  • Stephen P. Hunger
    Department of Pediatrics, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA;
  • Csongor Kiss
    Department of Pediatric Hematology and Oncology, Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary;
  • Hsi-Che Liu
    Division of Pediatric Hematology-Oncology, MacKay Memorial Hospital–MacKay Children's Hospital, Taipei, Taiwan;
  • Franco Locatelli
    Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale Pediatrico Bambino Gesù, Sapienza, Università di Roma, Rome, Italy;
  • Mignon L. Loh
    Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
  • Atsushi Manabe
    Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan;
  • Georg Mann
    Children's Cancer Research Institute–St Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria;
  • Rob Pieters
    Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands;
  • Ching-Hon Pui
    Department of Oncology, St Jude Children's Research Hospital, Memphis, TN;
  • Susana Rives
    Pediatric Hematology and Oncology Department, Hospital Sant Joan de Déu de Barcelona–Institut de Recerca Sant Joan de Déu, Barcelona, Spain;
  • Kjeld Schmiegelow
    Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet–Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark;
  • Lewis B. Silverman
    Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA;
  • Jan Stary
    University Hospital Motol–Second Faculty of Medicine, Charles University, Prague, Czech Republic;
  • Ajay Vora
    Great Ormond Street Hospital, London, United Kingdom; and
  • Patrick Brown
    Johns Hopkins Kimmel Cancer Center, Baltimore, MD

抄録

<jats:title>Abstract</jats:title> <jats:p>Comparison of treatment strategies in de novo pediatric acute lymphoblastic leukemia (ALL) requires standardized measures of efficacy. Key parameters that define disease-related events, including complete remission (CR), treatment failure (TF; not achieving CR), and relapse (loss of CR) require an updated consensus incorporating modern diagnostics. We collected the definitions of CR, TF, and relapse from recent and current pediatric clinical trials for the treatment of ALL, including the key components of response evaluation (timing, anatomic sites, detection methods, and thresholds) and found significant heterogeneity, most notably in the definition of TF. Representatives of the major international ALL clinical trial groups convened to establish consensus definitions. CR should be defined at a time point no earlier than at the end of induction and should include the reduction of blasts below a specific threshold in bone marrow and extramedullary sites, incorporating minimal residual disease (MRD) techniques for marrow evaluations. TF should be defined as failure to achieve CR by a prespecified time point in therapy. Relapse can only be defined in patients who have achieved CR and must include a specific threshold of leukemic cells in the bone marrow confirmed by MRD, the detection of central nervous system leukemia, or documentation of extramedullary disease. Definitions of TF and relapse should harmonize with eligibility criteria for clinical trials in relapsed/refractory ALL. These consensus definitions will enhance the ability to compare outcomes across pediatric ALL trials and facilitate development of future international collaborative trials.</jats:p>

収録刊行物

  • Blood

    Blood 139 (12), 1785-1793, 2022-03-24

    American Society of Hematology

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