Introduction on Chemotherapy-Induced Neutropenia
Dr. Lyman: So I’m a medical oncologist and hematologist at the Fred Hutchinson Cancer Research Center currently. I’ve been working in the area of cancer supportive care for several decades now. The role of neutropenia on patient outcomes and ways to reduce it or avoid it has been a central focus of my research for many years.
Well, neutropenia is the result of what we call myelosuppression. That is bone marrow suppression. Since neutrophils, the white cells in general, and red cells and platelets are produced in the bone marrow, anything that impacts and suppresses the development of those cells in the early stages of development can result in neutropenia, can result in anemia, can result in low platelets or thrombocytopenia. It turns out that neutropenia is the most profoundly affected of the cell lineages coming from the bone marrow when patients receive cytotoxic therapies for cancer. We often state, and it’s still true, that neutropenia is the most common dose limiting toxicity of traditional or conventional cancer chemotherapy which attacks rapidly proliferating cells, again in the bone marrow, but also in other parts of the body, the gastrointestinal tract, and so forth.
It is often in neutropenia, if it becomes too severe and puts that patient at too great a risk for infection, that limits how much chemotherapy a patient can receive safely. It may lead to modifications in the dose, delays in treatment, or even stopping treatment when it’s severe. So neutropenia is at the heart. Even though we’re very excited, I think the whole field of oncology is excited, about the newer targeted therapies and now, immunotherapies like checkpoint inhibitors. Many of these are given either after conventional cytotoxic therapy or in combination with such therapy. So I always tell my trainees that despite the excitement about these new therapies, which have revolutionized some aspects of oncology, conventional chemotherapy is going to be with us for the foreseeable future.
This issue of neutropenia will remain a major focus of attention when trying to get patients through treatment and protect them from serious and potentially life-threatening infection.
Obviously patients will be evaluated in terms of their hematopoietic function before they start chemotherapy or any kind of therapy. So they’ll have blood counts done. If for—in the unusual circumstances where those blood counts are already low because of other conditions like the bone marrow being involved with tumor, which occurs in more advanced patients, or other diseases that might affect the bone marrow, then a great deal of caution needs to be given. Once the patient begins chemotherapy, of course that focus becomes on how low the blood counts will go and when they’ll recover. However, much of the thrust in the field of oncology for protecting patients and providing aggressive supportive care, is to anticipate which patient will develop neutropenia or it’s consequences, febrile neutropenia which means a serious infection that may occur even though you don’t know where the infection is in the body. Patients may become septic, blood stream infection, or no clear focus of infection.
But if that fever occurs in the setting of severe neutropenia, with an absolute neutrophil count less than 500, or in very profound situations, less than 100, a fever in that setting is a life-threatening emergency and needs to be managed aggressively. It’s also important that patients be educated about the risk of neutropenia and the importance of being cautious, avoiding opportunities that might put them at risk for infection, family members or friends with infection, much of the same thing we’re going through now with COVID-19 is to avoid exposure to patients who might already have, in this case, the bigger problem being a bacterial infection that might pose a risk when the patient becomes neutropenic.
Again, severe febrile neutropenia, less than 500 with a fever, is indicative of an underlying serious infection that can be life-threatening. Now, historically, and my experience goes back sufficiently long before we had the hematopoietic growth factors or other ways of stimulating the bone marrow, and in that era and even earlier, febrile neutropenia could result in the death of a large proportion of patients going through cytotoxic therapy. Fortunately, very early in my career anyway, we had available, it became available, better and better antibiotics for treating serious infections. Broad spectrum, antimicrobial coverage with several antibiotics may reduce the mortality rate associated with serious infection in the setting of neutropenia. Although, it doesn’t prevent it entirely. Before that, – – certainly patients with leukemia, the mortality rate was extremely high and was a constant serious threat to the patient.
Despite the antibiotics, though, it was clear that most of the antibiotics don’t do anything about the bone marrow suppression and the neutropenia. They only reduce the risk, perhaps, of the infection becoming a fatal infection. So the introduction of the hematopoietic growth factors that stimulate bone marrow recovery and reduce the severity of neutropenia was a game changer in oncology. It has led to, at least patients who are deemed to be at serious risk of febrile neutropenia with conventional chemotherapy, it provides and opportunity to them to avoid or at least reduce the risk of those complications that can be serious and life-threatening. So the basic approach we take in oncology is, of course, we have treatments based largely on randomized controlled clinical trials that establish the efficacy of the chemotherapy and its safety. These are approved by the FDA. More and more over the years became combination chemotherapies.
The combinations had a better chance of controlling the disease or even curing the malignancy, but also raised the chance—increased the risk of neutropenia and febrile neutropenia. So it was always finding that balancing act. But with the hematopoietic growth factors and hopefully coming even more effective ways to prevent febrile neutropenia, we’re able to deliver more consistently to more patients the full dose of intended chemotherapy without putting them at serious risk of fatal complications from the chemotherapy itself.
So you look at the regimen you want to give to the patient, you look at the literature, what has been the experience in terms of neutropenic complications, you discuss it with the patient that there’s always some risk but we can reduce that risk substantially with aggressive supportive care. It may mean taking injections or getting—coming in and getting seen more often, but far better than dying of a serious infection. It also enables patients to stay on the treatment through the full course and have the best chance at beating the cancer, being cured of the malignancy. So the supportive care in this setting not only reduces the risk of an early, serious, life-threatening infection or even early death, but also enabling the patient to get the full course of chemotherapy that we know is associated with the best chance of beating the cancer. So it’s a double win if we’re able to achieve that with supportive care measures given along with the recommended chemotherapy.
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