What is the appropriate management for a patient with leukopenia and neutropenia, presenting with weight loss and night sweats?

Management of Leukopenia and Neutropenia with Constitutional Symptoms

This patient requires urgent bone marrow aspiration and biopsy with comprehensive workup for hematologic malignancy, as the combination of neutropenia (ANC 1100), leukopenia (WBC 3.1), weight loss, and night sweats strongly suggests an underlying lymphoproliferative disorder or other hematologic malignancy. 1

Immediate Diagnostic Evaluation

Essential Laboratory Studies

• Complete blood count with differential to fully characterize the pancytopenia pattern and identify any abnormal cell populations 1
• Peripheral blood smear examination by a qualified hematologist or pathologist to identify abnormal cells and detect morphologic abnormalities suggesting specific diagnoses 1
• Lactate dehydrogenase (LDH) as an indicator of cell turnover in hematologic malignancies 1
• HIV and hepatitis C testing given the presentation of constitutional symptoms with cytopenias 1

Critical Imaging and Bone Marrow Studies

• CT scan of chest, abdomen, and pelvis to evaluate for lymphadenopathy, assess spleen size, and identify hepatomegaly or other organomegaly 1
• Bone marrow aspiration and biopsy are essential given the constitutional symptoms and cytopenias, with morphologic evaluation, flow cytometry, cytogenetics, and immunohistochemistry 1
• Flow cytometry helps identify lymphoproliferative disorders and characterize cell populations 1
• Cytogenetics to detect clonal abnormalities 1

Differential Diagnosis Priority

High-Risk Hematologic Malignancies to Exclude

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Weight loss, night sweats, and fever without infection are specific indications for treatment initiation in CLL/SLL 2. Progressive cytopenia in the context of B symptoms requires immediate evaluation 2.

Waldenström's Macroglobulinemia: Characteristically presents with constitutional symptoms (recurrent fever, night sweats, weight loss, fatigue), cytopenias, and splenomegaly 2, 1. If lymphoplasmacytic infiltration is identified, obtain serum protein electrophoresis, immunofixation, quantitative immunoglobulins including IgM, and MYD88/CXCR4 mutation testing 1.

Hodgkin Lymphoma: B symptoms (unexplained fevers >38°C, drenching night sweats, or weight loss >10% body weight within 6 months) are defining features 2. In patients with HIV, B symptoms may indicate concurrent opportunistic infection if CD4 counts are low 2.

Hairy Cell Leukemia: Characteristically presents with pancytopenia and splenomegaly 1

Infection Risk Assessment and Management

Neutropenia Severity Classification

With an ANC of 1100/µL, this patient has mild neutropenia (ANC <1500/µL) 3. However, the risk stratification must consider:

• Duration of neutropenia (transient vs. chronic) 3
• Clinical status and presence of fever 3
• Underlying cause once identified 3

Febrile Neutropenia Protocol

If fever develops (temperature >38°C), immediate action is required:

• Empirical broad-spectrum antibiotics must be initiated promptly pending further workup 2
• Screen for SARS-CoV-2 in all patients with hematological malignancies and fever whenever possible 2
• The differential diagnosis for neutropenic fever remains broad despite COVID-19 considerations 2
• Cefepime monotherapy (2g IV every 8 hours) is FDA-approved for empiric treatment of febrile neutropenic patients, though insufficient data exist to support monotherapy in high-risk patients (history of recent bone marrow transplantation, hypotension at presentation, underlying hematologic malignancy, or severe/prolonged neutropenia) 4

Critical Pitfalls to Avoid

• Constitutional symptoms combined with pancytopenia significantly increase concern for serious pathology and should never be attributed to benign causes without thorough malignancy workup 1
• Delaying bone marrow examination can delay diagnosis of treatable malignancies 1
• Do not attribute neutropenia solely to medications (such as vancomycin, which typically causes neutropenia after ≥20 days of therapy) without excluding malignancy first in the setting of B symptoms 5
• Splenomegaly in the context of pancytopenia suggests either infiltrative disease or hypersplenism secondary to underlying hematologic disorder 1

Additional Considerations

Tuberculosis Evaluation

Tuberculosis evaluation is necessary as TB can cause constitutional symptoms and pancytopenia, including chest imaging and tuberculin skin testing or interferon-gamma release assay 1

Growth Factor Use

Avoid routine use of granulocyte colony-stimulating factor (G-CSF) until the underlying diagnosis is established, as growth factors should be avoided in patients with moderate-to-severe infections given potential risk of exacerbating inflammatory injury 2. G-CSF may be considered if high risk of febrile neutropenia (>20%) is identified after diagnosis 6.