Cancer chemotherapy can be a life-saver, but it is fraught with severe side effects, among them an increased risk of infection. Until now, the major criterion for assessing this risk has been the blood cell count: if the number of white blood cells falls below a critical threshold, the risk of infection is thought to be high.
The study, recently published in the Journal of Clinical Investigation, brought together the expertise of researchers from such diverse disciplines as applied mathematics, electrical engineering, oncology, immunology and pediatrics.
The model has already offered a plausible explanation for a number of medical mysteries. It helps explain, for example, 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 the smallest numbers of bacteria, for example, those present in the gut, can tilt the fragile immune balance in favor of the bacteria.
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 levels. The chemotherapy lowers both neutrophil levels and function, making the tissues of these patients more penetrable to bacteria. The model suggests that as a result, in some patients the bacterial concentrations might increase so quickly that by the time the neutrophil counts rise back to “normal,” the rapidly multiplying bacteria have already gained a head start, so that the neutrophil recovery is insufficient for overcoming the infection. This scenario may eventually also shed light on the rare cases in which acute bacterial infections develop in individuals with normal immunological function. The model suggests that in such cases, a high growth rate of unusually virulent bacteria could overcome the appropriate quantitative and qualitative neutrophil response.
Certain puzzling medical cases could be clarified thanks to the model. For example, a newborn baby treated at Meir Medical Center recovered from neutropenia even though his absolute neutrophil count (ANC) had fallen as low as 200 neutrophils per microliter of blood, whereas an adult whose ANC stood at 380 after chemotherapy died of infection. The model has suggested how such clinical parameters as the poor quality of the neutrophils might have lead to the death of the adult. In addition, the model could help doctors to understand the mechanism behind the development of severe recurrent infections in some patients. Of one thousand patients referred to Meir Medical Center because of such infections, diagnosis could be established in only one-third of the cases. Weizmann Institute’s mathematical modeling suggests that at least some of the unresolved cases may have resulted from a combination of several mild defects, including variation in the function of neutrophils and other immune cells.The study was performed by researchers with an unusual combination of backgrounds. Lead author, Weizmann Institute’s mathematician Prof. Vered Rom-Kedar, specializes in the investigation of dynamic systems. The first author, Dr. Roy Malka, an electrical engineer who has become an applied mathematician, conducted this research as part of his Ph.D. studies at Weizmann; he is now conducting postdoctoral research on related subjects at Harvard Medical School. The idea for the project was first proposed by Dr. Eliezer Shochat, a senior oncologist who also has a Ph.D. in applied mathematics from Weizmann and now works in a research group at Hoffman-La Roche in Basel, Switzerland. The study was performed in collaboration with the Meir Medical Center team: Prof. Baruch Wolach, M.D., Head of the Laboratory for Leukocyte Function and Chair of Pediatric Immunology at Tel Aviv University’s Sackler Faculty of Medicine; and laboratory manager Ronit Gavrieli, M.Sc., who performed the experiments.
Yivsam Azgad | EurekAlert!
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