MONZA, Italy – Teaching the immune system to attack high-risk acute lymphoblastic leukemia (ALL) and turning it into an ally against leukemia in children and adolescents is possible. This is the conclusion of the AIEOP-BFM ALL 2017 study, a long and complex international clinical trial in which two cycles of high-intensity chemotherapy were compared with two cycles of immunotherapy in patients at high risk of relapse.
The results provide strong evidence that this strategy can almost halve the number of relapses while significantly reducing severe side effects associated with intensive chemotherapy.
The findings were published in the New England Journal of Medicine, one of the world’s leading international scientific journals.
A new approach for patients at high risk of relapse
The study opens new prospects for pediatric patients with a particularly difficult-to-treat form of leukemia and a higher risk of relapse.
In these children, efforts to prevent relapse have traditionally required particularly intensive chemotherapy regimens. While effective, these treatments can cause serious—and in some cases life-threatening—side effects.
Current intensive chemotherapy regimens allow approximately 90% of children with acute lymphoblastic leukemia to achieve long-term survival. However, around one in five patients belongs to a specific high-risk category, meaning that they face a substantially higher probability of relapse.
The AIEOP-BFM ALL 2017 trial focused specifically on these children, investigating whether part of the most aggressive chemotherapy could be replaced with a targeted immunotherapy based on blinatumomab.
Harnessing the immune system against leukemia
Blinatumomab works by harnessing the patient’s own immune system. The drug brings T lymphocytes, key cells of the body’s immune defenses, into direct contact with leukemia cells.
This interaction enables immune cells to recognize and destroy cancer cells more effectively, offering a more targeted approach than conventional chemotherapy.
According to Andrea Biondi, Scientific Director of the Tettamanti Foundation and principal investigator for Italy in the AIEOP-BFM ALL 2017 study, the goal was to improve the chances of cure while reducing the toxicity of treatment for children and minimizing its impact on their families.
“The objective of this important study […] was to try to further improve the chances of cure, reducing as much as possible the toxicity of treatment for children and its impact on families.”
The study involved more than 100 research centers across eight European and non-European countries, making it a major international collaborative effort.
Decades of international collaboration
The trial is the result of a collaboration spanning several decades between AIEOP and the German Berlin-Frankfurt-Münster Group for Acute Lymphoblastic Leukemia (BFM), which served as co-sponsors for Italy and Germany, respectively.
The partnership dates back to the first international protocol launched in 1998. Since then, Italy has played an active role in the development and implementation of numerous major international protocols for the treatment of childhood acute lymphoblastic leukemia.
For Italy, AIEOP appointed the Tettamanti Foundation as the National Coordinating Center (NCC). The Foundation was responsible for project management, monitoring visits to participating centers, pharmacovigilance, insurance coverage, statistical analyses, and data analysis.
The coordination effort required an annual financial commitment of more than €1.2 million.
A national network supporting precision treatment
The study also involved the Pediatric Oncology Center of the University of Padua and the Fondazione Città della Speranza in Padua, which contributed to centralized diagnosis and monitoring of diseases diagnosed in Italian children and adolescents.
Together with other institutions within the Italian leukemia research network, these centers have played a significant role in clinical research and in supporting clinical trials for childhood leukemia.
The Tettamanti Research Center, supported by the Fondazione Maria Letizia Verga of Monza, has also contributed to the development of increasingly precise and targeted approaches, including complex biological studies and genetic profiling with prognostic value. These tools have been made available to children with acute lymphoblastic leukemia throughout Italy.
Toward earlier and more targeted immunotherapy
The results of the AIEOP-BFM ALL 2017 trial strengthen the case for integrating immunotherapy earlier and more effectively into the treatment pathway for pediatric acute lymphoblastic leukemia.
The aim goes beyond increasing cure rates. By replacing some of the most aggressive treatments with more selective and better-tolerated approaches, researchers hope to reduce both the immediate and long-term consequences of intensive therapy.
For children facing high-risk leukemia, the findings therefore represent an important step toward treatment strategies that combine effective disease control with a greater focus on minimizing the burden of therapy.
Contact
Prof. Andrea Biondi
Scientific Director of the Tettamanti Foundation