What is the most likely reason for the increase in White Blood Cells (WBCs)/neutrophils from the previous Complete Blood Count (CBC)?

Administration of Granulocyte Colony-Stimulating Factor (G-CSF) is the Most Likely Reason for the Increase in WBCs/Neutrophils

The most likely reason for the increase in white blood cells (WBCs)/neutrophils from the previous CBC is the administration of granulocyte colony-stimulating factor (G-CSF) to treat the patient's severe neutropenia before the scheduled chemotherapy. 1

Rationale for G-CSF Administration in This Case

The patient's clinical scenario strongly suggests G-CSF administration for several reasons:

1. Severe neutropenia: The patient had an absolute neutrophil count of 200/μL, which represents severe neutropenia (ANC < 500/μL)

2. Aggressive chemotherapy: The patient is receiving aggressive chemotherapy for non-Hodgkin's lymphoma that did not respond to initial treatment 1

3. Rapid recovery: The significant increase in neutrophil count within a few days is characteristic of G-CSF administration, which typically produces a marked increase in circulating neutrophils within 24-72 hours 2

Mechanism of Action

G-CSF works through several mechanisms:

• Binds to specific cell surface receptors on hematopoietic cells, stimulating proliferation and differentiation of neutrophil precursors 2
• Regulates neutrophil production within the bone marrow 2
• Enhances neutrophil release from bone marrow storage pools 3
• Produces a dose-dependent increase in circulating neutrophil counts 2

Expected Hematologic Response to G-CSF

When G-CSF is administered:

• White blood cell differentials demonstrate a shift toward earlier granulocyte progenitor cells (left shift) 2
• Promyelocytes and myeloblasts may appear during neutrophil recovery 2
• These changes are transient and not associated with clinical sequelae 2
• Neutrophil counts typically increase within hours to days after administration 4

Clinical Guidelines Supporting G-CSF Use in This Scenario

The American Society of Clinical Oncology guidelines recommend:

• G-CSF administration after chemotherapy in patients with severe neutropenia, particularly when:

  • The patient is receiving aggressive chemotherapy regimens 1
  • There is a history of febrile neutropenia or severe neutropenia 1
  • The patient has additional risk factors (such as prior chemotherapy exposure) 1

• Secondary prophylaxis with CSFs is recommended for patients who experienced neutropenic complications from prior chemotherapy cycles, especially when dose reduction may compromise treatment outcome 1

Alternative Explanations (Less Likely)

1. Spontaneous bone marrow recovery: While possible, the rapid increase in neutrophils within days is more consistent with G-CSF administration than spontaneous recovery 4

2. Infection-induced leukocytosis: Infection can cause increased WBCs, but the timing and context strongly favor G-CSF as the cause 5

3. Stress response: Physiological stress can increase neutrophil counts but typically not to the degree seen with G-CSF administration 1

Clinical Implications

• G-CSF administration allows for timely delivery of scheduled chemotherapy by accelerating neutrophil recovery 1
• This approach helps maintain dose intensity of chemotherapy, which is particularly important in aggressive lymphomas 1
• The transient changes in WBC morphology (left shift, appearance of immature forms) should not be mistaken for disease progression 2

Common Pitfalls to Avoid

• Misinterpreting the left shift and appearance of immature forms as infection rather than G-CSF effect 2
• Failing to recognize that G-CSF-induced neutrophilia is a therapeutic effect, not a pathological response 6
• Delaying chemotherapy unnecessarily when neutrophil recovery is adequate for treatment 1

G-CSF administration represents standard of care in managing chemotherapy-induced neutropenia in this pediatric patient with non-Hodgkin's lymphoma receiving aggressive chemotherapy, and is the most likely explanation for the observed increase in WBCs/neutrophils.