Acute lymphoblastic leukemia (ALL) is the most common malignant disease in childhood. Although the overall survival rate in Spain is 85%, it falls below 50% among patients who suffer a relapse or do not respond to chemotherapy. To find solutions for children facing these relapses and improve their treatment options, the Spanish Society of Pediatric Hematology and Oncology (SEHOP) created ReALLNet (Relapsed Acute Lymphoblastic Leukemia Network) in 2021: a network that, for the first time, brings together more than 60 physicians and researchers from all Spanish centers treating childhood cancer, using approaches ranging from precision medicine to artificial intelligence in order to find solutions for these children and improve their chances of survival.

ReALLNet is a national initiative of experts aimed at improving the diagnosis and treatment of children with relapsed acute leukemia. The network is coordinated through SEHOP by Pablo Velasco, pediatrician in the Pediatric Oncology and Hematology Department at Vall d’Hebron University Hospital and researcher in the Childhood Cancer and Blood Disorders group at the Vall d’Hebron Research Institute (VHIR), and by José Luis Fuster, Head of the Pediatric Oncology and Hematology Department at Virgen de la Arrixaca Clinical University Hospital and member of the Pascual Parrilla Murcia Institute for Biosanitary Research (IMIB). It is supported by the Josep Carreras Foundation, which funds the project with a contribution of €1.4 million, and by the Unoentrecienmil Foundation.

Its main objective is to ensure that all patients have access to the same diagnostic and therapeutic opportunities, regardless of the hospital where they receive care. To illustrate the significance of the network’s work, Dr. Velasco explains that “the relapse rate is 13% in acute lymphoblastic leukemia, with an estimated 50 new cases per year; and reaches 30% in myeloblastic leukemia, with an incidence of 15 new cases per year. Overall, we estimate there will be around 60 to 70 cases annually.” Dr. Fuster adds a figure that summarizes the challenge: “After the first relapse, the chances of long-term survival fall below 50%.”

Identifying high-risk genetic alterations

Since its launch in 2021, this pioneering initiative has succeeded in building a collaborative infrastructure that brings together, on a voluntary basis, clinical specialists, researchers, experts in genetics, bioinformatics and artificial intelligence, as well as representatives of patient family associations.

Project advances were shared on October 8 and 9 at the 4th ReALLNet Workshop, an event that served to update and review the network’s results and define its clinical and research strategy for the coming year.

One of the project’s most significant milestones is the creation of the largest Spanish registry of pediatric leukemia relapses, which already includes more than 400 registered patients. In addition, more than 80 children have been studied using advanced precision medicine techniques, including RNA sequencing, functional studies and complex omics analyses.

Preliminary results show that these technologies have made it possible to identify high-risk genetic alterations and facilitate personalized treatments that, in some cases, have achieved remission in diseases with very few therapeutic alternatives.

Furthermore, some of the innovations developed through ReALLNet are already being transferred to research platforms beyond Spain.

Direct impact on pediatric patients with relapsed disease

Thanks to the creation of this collaborative network, complex cases are reviewed weekly by a national multidisciplinary committee and, in some situations, by European expert panels. In addition, a ReALLNet working group has developed an algorithm to identify the most appropriate clinical trial for pediatric cancer patients, a pioneering non-commercial initiative in Europe.

Dr. Pablo Velasco notes that “ReALLNet has become Spain’s largest collaborative platform for addressing childhood leukemia relapses, combining precision medicine, artificial intelligence and cooperation among hospitals to improve treatment options for the most complex patients.”

At the same time, ReALLNet is developing artificial intelligence tools to analyze large volumes of clinical and biological data, generate predictive response models, and facilitate the identification of suitable clinical trials for each patient. These initiatives have already attracted international interest and could be expanded to other European countries.

Antoni Garcia, manager of the Josep Carreras Foundation, highlights that “this initiative marks a turning point in the fight against childhood leukemia in Spain. Bringing all hospital centers together under a single collaborative network allows us to provide a coordinated, cutting-edge response to children and families facing the most difficult moment: relapse.” He adds: “Our commitment is clear: we will not give up while even one child remains without therapeutic alternatives, and precision medicine is currently our best tool for restoring hope.” Elena Huarte-Mendicoa, General Director of the Unoentrecienmil Foundation, adds that “when we invited all these physicians and researchers several years ago to share their experiences and concerns at our headquarters, we realized how important it was to support them. Their vision of integrating artificial intelligence to achieve more accurate predictions about disease behavior in the future aligned perfectly with our innovation strategy in research.”