New Directions in Chemotherapy-Induced Neutropenia - Episode 3
A clinician’s recommendations for appropriately monitoring patients with cancer for chemotherapy-induced neutropenia or other infections.
Lee Schwartzberg, MD, FACP: The first component in monitoring and preventing CIN [chemotherapy-induced neutropenia] in practice is to understand the myelosuppressive intensity of the chemotherapy that you’re giving to a patient, and it’s also important to look at a list of potential patient and disease factors that might impact that more negatively as well.
You might have a regimen that has an intermediate risk of CIN and FN [febrile neutropenia] in that 10% to 20% range, but you might have that patient being elderly with multiple comorbidities and extensive bone marrow involvement. You know that patient has a higher risk of CIN.
We also need to know by the regimen when the CIN occurs. It’s not an immediate event. Remember, the chemotherapy is impacting the hematopoietic stem cells in the bone marrow that are constantly making neutrophils. It takes many days for a neutrophil to go from a committed stem cell to a fully mature neutrophil and to be released from the bone marrow into the circulation where it can fight infection. Chemotherapy slows that process, and therefore, depending on the chemotherapy you get, that could be anywhere from around 8 days to about 14 days after the chemotherapy when it hits its nadir, the lowest point in the neutrophil count.
It is important to think about monitoring patients, particularly in their first cycle of therapy, to see how low they go and whether or not they develop CIN. Now, mild CIN is usually not of great consequence, but severe CIN with a neutrophil count of less than 1000 [per μL], which is grade 3, or less than 500 [per μL], which is grade 4, is where we start to see the risk for fever and infection developing.
We’ve known for decades now that the risk of febrile neutropenia is directly related to the depth of the nadir, how low the white blood cell count, particularly the neutrophil count, goes and how long it stays low. In patients treated even in the 1960s, this relationship with low neutrophil count and duration of neutropenia was established. If you have a neutrophil count below 500 [per μL], but it lasts for several days, that risk goes up substantially. If you have a neutrophil count that goes down to zero, which can happen with chemotherapy, that risk is high almost immediately, within a day or two. And even if you have a neutrophil count that’s below 1000 [per μL], if it lasts for several days or longer, those patients are at risk for getting febrile neutropenia. It’s the product of the time of neutropenia and the depth of neutropenia that gives you the risk of febrile neutropenia and infection and complications.