Despite exciting advances in pediatric acute lymphoblastic leukemia (ALL) treatment and research, substantial variability in definitions for key outcomes has limited data comparisons across clinical trials. To address this important gap, the Ponte-di-Legno (PdL) Consortium developed international consensus definitions of complete remission, treatment failure, and relapse to be used in pediatric ALL trials, as published in 2022 and highlighted below.1,2

Complete remission (CR)

According to the authors, the current “gold standard” approach for the assessment of CR is measurement of minimal residual disease (MRD) using standardized methods such as polymerase chain reaction (PCR), flow cytometry, or next-generation sequencing (NGS) technologies. Cytomorphology may be used to assess CR when MRD is unavailable.

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CR should be assessed no earlier than end of induction (EOI) and is defined as: MRD <1% or bone marrow blasts <5% (M1) on microscopy; CNS1 status on CSF cytomorphology, clinical neurological exam, as well as CNS imaging when indicated; and no evidence of extramedullary disease on clinical exam and imaging, with reduction of any preexisting leukemic mass to at least one-third of the initial size.

Treatment failure (TF)

The Consortium agreed that TF should be defined as failure to achieve CR by a time point specified at the start of the clinical trial. “There was progress toward a consensus that a TF event is to be defined no earlier than the [end of consolidation], because this would allow a patient not achieving CR by EOI to be offered a consolidation therapy with agents not given during induction in an effort to overcome blast resistance and potentially achieve CR,” as explained in consensus statement.1


The authors noted that relapse can only occur in patients who have previously achieved CR and should be subclassified based on the involved anatomic sites as follows: isolated bone marrow relapse, isolated CNS relapse, isolated testicular relapse, isolated other extramedullary relapse, or a combination of these sites. For bone marrow relapse, the percentage of blasts should ideally be determined via MRD techniques, with the addition of 1 or 2 additional sensitive diagnostic tests demonstrating ≥1% blasts if MRD is ≥5% or ≥1%, respectively.

Although the Consortium members acknowledge the limited availability of MRD methodologies in low- and middle-income countries, they expect the consensus definitions to enable greater overall uniformity in the interpretation of treatment outcomes in pediatric ALL.1

We checked in with experts in the field to gauge clinician perspectives on the PdL updates: Rabi Hanna, MD, director of Pediatric Bone Marrow Transplantation at Cleveland Clinic Children’s Hospital in Ohio; David Teachey, MD, physician and researcher with the Cancer Center at Children’s Hospital of Philadelphia and associate professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania; and Kelly Maloney, MD pediatric hematologist/oncologist at Children’s Hospital Colorado and associate professor of pediatrics in the section of hematology, oncology, and bone marrow transplantation at the University of Colorado Anschutz Medical Campus in Aurora.