Does preoperative neutropenia (low neutrophil count) require treatment?

From the Guidelines

Preoperative neutropenia should be treated with granulocyte colony-stimulating factor (G-CSF; filgrastim) or its biosimilar to reduce the incidence of myelosuppression and infections, and the treatment should be continued until the absolute neutrophil count (ANC) is at least 500/mm3. This approach is supported by recent guidelines, such as those outlined in the 2024 expert consensus guidelines on management and best practices for tumor-infiltrating lymphocyte cell therapy 1. According to these guidelines, G-CSF can be safely initiated the day after TIL infusion and is strongly recommended to mitigate the risks associated with neutropenia.

Key considerations in the management of preoperative neutropenia include:

• The severity of neutropenia, with severe cases (ANC <500/mm³) requiring prompt treatment
• The presence of symptoms, which may necessitate more aggressive management
• The planned surgical procedure and its associated infection risk
• The need for individualized decision-making based on the patient's specific circumstances

In terms of treatment specifics, filgrastim or its biosimilar can be administered at 5 μg/kg/day subcutaneously daily, starting from the day after the relevant infusion or as deemed necessary by the clinical context, until neutropenia is resolved 1. It's also crucial to monitor complete blood counts daily and provide supportive care, such as transfusions of platelets and packed red blood cells as needed, to maintain hemoglobin levels at ≥7.0 g/dL and platelets >30,000/mm³, unless otherwise indicated by institutional standards or patient comorbidities.

From the FDA Drug Label

INDICATIONS AND USAGE ZARXIO is a leukocyte growth factor indicated to • Decrease the incidence of infection‚ as manifested by febrile neutropenia‚ in patients with nonmyeloid malignancies receiving myelosuppressive anti‑cancer drugs associated with a significant incidence of severe neutropenia with fever (1. 1) • Reduce the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML) (1.2) • Reduce the duration of neutropenia and neutropenia-related clinical sequelae‚ e.g. ‚ febrile neutropenia, in patients with nonmyeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation (BMT) (1.3) • Mobilize autologous hematopoietic progenitor cells into the peripheral blood for collection by leukapheresis (1.4) • Reduce the incidence and duration of sequelae of severe neutropenia (e.g. ‚ fever‚ infections‚ oropharyngeal ulcers) in symptomatic patients with congenital neutropenia‚ cyclic neutropenia‚ or idiopathic neutropenia (1.5) • Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome) (1. 6)

The answer to whether to treat pre-op neutropenia is not directly addressed in the provided drug labels. However, neutropenia is a condition where the patient has a low neutrophil count, and the labels discuss the use of filgrastim to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anti-cancer drugs.

• The labels do provide dosage information for patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia 2, 2. However, the labels do not explicitly address the treatment of pre-op neutropenia. Therefore, based on the provided information, no conclusion can be drawn regarding the treatment of pre-op neutropenia with filgrastim.

From the Research

Treatment of Preoperative Neutropenia

• The decision to treat preoperative neutropenia depends on the underlying cause and severity of the condition 3, 4.
• According to the study by 3, G-CSF and GM-CSF are used to promote the production of granulocytes and are approved for the treatment of congenital and acquired neutropenias.
• However, the study by 5 suggests that preoperative neutropenia may not be a significant risk factor for early catheter-related bloodstream infections in newly diagnosed pediatric cancer patients, and that postoperative neutropenia is a more significant concern.
• The management of severe chronic neutropenia includes aggressive treatment of bacterial or fungal infections, and administration of G-CSF 4.
• In patients with leukocyte abnormalities suspected on primary haematologic disorder, treatment generally involves preventing infections, managing febrile neutropenia with broad spectrum antibiotics and antifungal drugs, and treatment with recombinant granulocyte hematopoetic factor 6.

Use of G-CSF in Neutropenia Treatment

• G-CSF is widely used to treat neutropenia associated with myelosuppressive chemotherapy and bone marrow transplantation, AIDS-associated or drug-induced neutropenia, and neutropenic diseases 3, 7.
• The use of G-CSF has been shown to facilitate restoration of neutrophil counts, decrease the incidence of infection/febrile neutropenia, and reduce resource utilization 7.
• However, G-CSF is expensive and requires systemic administration, and the development of biosimilars and next-generation compounds may offer alternative treatment options 7.

Preoperative Preparation

• The complete peripheral blood count analysis, including laboratory screening tests of haemostasis and coagulation, should be done in every patient before surgery to detect specific abnormalities for primary or secondary haematologic disorder 6.
• Patients with leukocyte abnormalities suspected on primary haematologic disorder need urgent haematologic diagnostic procedures, and treatment generally involves preventing infections and managing febrile neutropenia 6.