i3S discovers treatment that enhances chemotherapy against acute myeloid leukaemia

A team of i3S researchers has identified a new therapeutic strategy, now published in Science Translational Medicine, which may improve the effectiveness of chemotherapy and reduce serious complications associated with the treatment of acute myeloid leukaemia.

The group, led by Delfim Duarte, demonstrated that the administration of transferrin — a protein that transports iron in the bloodstream — in combination with chemotherapy improves bone marrow recovery, increases survival, and reduces infectious complications associated with conventional therapy.

Acute myeloid leukaemia is, in most cases, treated with intensive chemotherapy. “Although it effectively eliminates cancer cells, this treatment causes significant toxicity, namely the excessive accumulation of iron in tissues,” explains Delfim Duarte, haematologist at IPO Porto and leader of the i3S research group Hematopoiesis and Microenvironments. In this study, the researchers tested the administration of human apotransferrin, an iron-free form of transferrin, to capture this excess mineral and redistribute it to healthy cells in the bone marrow and immune system.

Using various experimental models, including mice with leukaemia, the team demonstrated that this approach significantly reduces levels of toxic circulating iron following chemotherapy.

New therapy strengthens the fight against severe infections

The team also examined the safety of this strategy in the context of severe infection, one of the leading causes of death in patients with acute myeloid leukaemia. In an experimental model of E. coli infection, animals treated with apotransferrin survived longer. “This was not because the bacteria were eliminated, but due to a more controlled inflammatory response. Apotransferrin reduced excessive inflammation, helping the body to better cope with the infection,” explains Marta Lopes, first author of the study.

Based on these “promising preclinical data”, the team hopes to move forward in the near future with a clinical trial, in collaboration with the early-phase trials unit at IPO Porto, to evaluate the use of transferrin as an adjuvant therapy to chemotherapy. “The goal is to preliminarily assess the safety and effectiveness of this combination [transferrin and chemotherapy] in patients with acute myeloid leukaemia,” concludes Delfim Duarte.