Mathematical model may reduce infections from chemotherapy

A new mathematical model suggests that proper risk assessment for the risk of infection with cancer chemotherapy needs to evaluate both the quantity and quality of white blood cells. The model was built by Weizmann Institute mathematicians in collaboration with physicians from the Meir Medical Center in Kfar Saba and from the Hoffman-La Roche research center in Basel, Switzerland. The study was published in Journal of Clinical Investigation.

Though chemotherapy for cancer can save lives, it also can have severe side effects, including an increased risk of infection. Currently, the major criterion to assess the risk of infection is the blood cell count, where the risk of infection is considered high if the number of white blood cells falls below a critical threshold. Neutropenia occurs when levels of white blood cells, mainly neutrophils, are dangerously low. This condition often emerges after chemotherapy or bone marrow transplant, and severe infections can develop if the immune system does not perform its crucial function of devouring and destroying bacteria.

“Our mathematical model has revealed previously unknown mechanisms responsible for the variability in the vulnerability of neutropenia patients to infections,” says research leader Professor Vered Rom-Kedar of the Weizmann Institute's Computer Science and Applied Mathematics Department.

The model finds that variety in the effectiveness of neutrophils between healthy people usually has no significant consequences. However, for patients with neutropenia, the individual variability can make the difference between life and death. The study has drawn this conclusion based on analyzing blood from four healthy volunteers, and the analysis needs to be applied to large populations for the model to be used in the clinic.

The model explains why acute infections develop in certain patients after chemotherapy or a bone marrow transplant, even if their neutrophil levels have returned to relatively normal levels. Chemotherapy lowers both neutrophil levels and function, so the tissues of these patients are more penetrable to bacteria. The model suggests that this results in a rapid increase in bacterial concentrations that gives a head start to the bacteria, and then the neutrophil recovery is insufficient to overcome the infection.

“Our study suggests that to achieve optimal results in applying chemotherapy, and/or in patients with innate neutrophil dysfunction, it is of value to assess the patient's neutrophils periodically, as well as the bacterial concentration. Such assessments will help reduce the morbidity and the mortality, as well as the cost, associated with unnecessary hospitalizations and the administration of expensive medications. Moreover, by cutting down on the use of antibiotics, these assessments can help in preventing the rise in antibiotic resistance,” stated Professor Baruch Wolach, MD, of Tel Aviv University's Sackler Faculty of Medicine and one of the study authors.
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