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

TY - JOUR

T1 - Remission, treatment failure, and relapse in pediatric ALL: An international consensus of the Ponte-di-Legno Consortium

AU - Buchmann, Swantje

AU - Schrappe, Martin

AU - Baruchel, Andre

AU - Biondi, Andrea

AU - Borowitz, Michael J

AU - Campbell, Myriam

AU - Cario, Gunnar

AU - Cazzaniga, Giovanni

AU - Escherich, Gabrielle

AU - Harrison, Christine J

AU - Heyman, Mats

AU - Hunger, Stephen P

AU - Kiss, Csongor

AU - Liu, Hsi-Che

AU - Locatelli, Franco

AU - Loh, Mignon L

AU - Manabe, Atsushi

AU - Mann, Georg

AU - Pieters, Rob

AU - Pui, Ching-Hon

AU - Rives, Susana

AU - Schmiegelow, Kjeld

AU - Silverman, Lewis B

AU - Stary, Jan

AU - Vora, Ajay

AU - Brown, Patrick A

AU - Ponte-di-Legno Consortium

N1 - Copyright © 2021 American Society of Hematology.

PY - 2022/3/24

Y1 - 2022/3/24

N2 - 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.

AB - 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.

U2 - 10.1182/blood.2021012328

DO - 10.1182/blood.2021012328

M3 - SCORING: Review article

C2 - 34192312

VL - 139

SP - 1785

EP - 1793

JO - BLOOD

JF - BLOOD

SN - 0006-4971

IS - 12

ER -