RESUMO
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, with survival rates exceeding 85%. However, 15% of patients will relapse; consequently, their survival rates decrease to below 50%. Therefore, several research and innovation studies are focusing on pediatric relapsed or refractory ALL (R/R ALL). Driven by this context and following the European strategic plan to implement precision medicine equitably, the Relapsed ALL Network (ReALLNet) was launched under the umbrella of SEHOP in 2021, aiming to connect bedside patient care with expert groups in R/R ALL in an interdisciplinary and multicentric network. To achieve this objective, a board consisting of experts in diagnosis, management, preclinical research, and clinical trials has been established. The requirements of treatment centers have been evaluated, and the available oncogenomic and functional study resources have been assessed and organized. A shipping platform has been developed to process samples requiring study derivation, and an integrated diagnostic committee has been established to report results. These biological data, as well as patient outcomes, are collected in a national registry. Additionally, samples from all patients are stored in a biobank. This comprehensive repository of data and samples is expected to foster an environment where preclinical researchers and data scientists can seek to meet the complex needs of this challenging population. This proof of concept aims to demonstrate that a network-based organization, such as that embodied by ReALLNet, provides the ideal niche for the equitable and efficient implementation of "what's next" in the management of children with R/R ALL.
RESUMO
The association between mature B-cell phenotype and KMT2A rearrangements in acute lymphoblastic leukemia is a very rare finding. It identifies a group of patients with similar clinical and biological characteristics that clearly differs from the entity B-cell lymphoblastic leukemia/lymphoma with t(v;11q23)/KMT2A-rearranged, which typically presents an immature pro B-cell phenotype. We describe the clinical-biological characteristics and disease outcome of three pediatric ALL patients with these features treated at our institution, and review 28 cases described in the literature. Most cases occur in children under 2 years-old, presenting a mature B-cell phenotype that uniformly expresses cytoplasmic and surface IgM with lambda light chain restriction, with heterogeneous co-expression of immaturity antigens. Patients do not have MYC rearrangements and all show KMT2A abnormalities, with 76% presenting t(9;11)(p21;q23)/MLLT3-KMT2A. These patients have an unfavorable clinical outcome and a 48% relapse rate. In-depth knowledge of this disease entity is needed to improve outcome.
