Waning white blood-cell counts in chemotherapy patients are commonly taken as a warning of an increased risk of infection.
Now, a new Israeli study suggests that it is critical to evaluate not only the quantity of these “neutrophil” blood cells essential to immunity against infection, but also their quality, which varies from one patient to another.
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The new model for evaluating infection risk comes out of research by Weizmann Institute of Science mathematicians in collaboration with physicians from the Meir Medical Center in Kfar Saba and the Hoffmann-La Roche research center in Basel, Switzerland.
Their research, recently published in the Journal of Clinical Investigation, may represent an important step in the emerging field of personalized medicine, leading to a more individualized approach to chemotherapy.
Based on an analysis of each patient’s neutrophils, it could be possible to take better precautions to prevent infection in high-risk patients, while those at a low risk could be spared unnecessary preventive treatments.
Multidisciplinary approach
The multidisciplinary study was done by researchers with expertise in applied mathematics, electrical engineering, oncology, immunology and pediatrics. The lead author, Prof. Vered Rom-Kedar, heads the Weizmann Institute’s Moross Research School of Mathematics and Computer Science. The first author, applied mathematician Roy Malka, formerly an electrical engineer, conducted this research as part of his PhD studies at Weizmann. This year he is a post-doc at Harvard Medical School.
The idea for the project was proposed by Dr. Eliezer Shochat, an oncologist trained in applied mathematics at the Weizmann and now working with the Hoffman-La Roche research group at in Basel. Partners at the Meir Medical Center included Dr. Baruch Wolach, head of the Laboratory for Leukocyte Function and chairman of pediatric immunology at Tel Aviv University’s Sackler Faculty of Medicine; and laboratory manager Ronit Gavrieli, who performed the experiments.
“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,” said Wolach. “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.”
He added that by cutting down on the use of antibiotics, these assessments can help prevent the rise of “superbug” bacteria resistant to antibiotics.
Helping to solve medical mysteries
Chemotherapy or bone marrow transplant patients with dangerously low levels of white blood cells, mainly neutrophils, are at risk of severe infections because their fragile immune system cannot combat invasive bacteria.
The Israeli model suggests that this is not simply an issue of numbers.
In most healthy people, the researchers believe, it doesn’t much matter how effective their individual neutrophils are against bacteria because the immune system as a whole can function fine. But in patients with compromised immune systems, individual variability can make a difference between life and death.
This model helps explain why, after chemotherapy, some cancer patients contract life-threatening infections even when in isolation under sterile conditions: If the neutrophils of these patients are “weak,” even a modest onslaught of bacteria can overpower the immune system.
The study also explains why certain patients, following chemotherapy or a bone marrow transplant, may develop acute infections even if their neutrophil levels have returned to relatively normal. Chemotherapy lowers the ability of neutrophils to fight off bacteria. The bacterial concentrations might increase so quickly that by the time the neutrophil counts rise to normal levels, the rapidly multiplying bacteria have already gained a head start.
In addition, Weizmann Institute’s mathematical modeling could shed light on the mechanism behind the development of severe recurrent infections in some patients. At least some mysterious cases may result from a combination of several mild defects, including variation in the function of neutrophils and other immune cells.
