What is the next step in management for a patient with suspected Hodgkin lymphoma, severe anemia, and evolving pancytopenia?

Next Step in Management: Complete Diagnostic Confirmation Before Treatment Initiation

The immediate priority is to obtain definitive tissue diagnosis through excisional lymph node biopsy or core needle biopsy of an accessible lymph node to confirm Hodgkin lymphoma before initiating any lymphoma-directed therapy. 1, 2

Rationale for Diagnostic Confirmation First

The bone marrow findings are highly suggestive but not diagnostic of Hodgkin lymphoma. The presence of "scattered large atypical cells suspicious for Reed-Sternberg cells" and "focal polymorphous lymphoid infiltrates" requires definitive confirmation from lymph node tissue, which is the gold standard for Hodgkin lymphoma diagnosis. 1 Bone marrow involvement alone, particularly with a dry tap and these findings, cannot definitively establish the diagnosis or subtype classification required for treatment planning.

Immediate Concurrent Management Steps

While arranging diagnostic biopsy, several critical actions must be taken:

Address Severe Anemia and Evolving Pancytopenia

• Transfuse packed red blood cells immediately to correct the severe anemia (Hb [LAB_VALUE] g/dL), as this degree of anemia significantly impacts quality of life and organ perfusion. 3
• Monitor complete blood counts daily to track the progression of pancytopenia, particularly the absolute neutrophil count and platelet count. 1
• Assess for active infection given the fever, splenomegaly, and borderline leukopenia—obtain blood cultures, chest imaging, and consider empiric broad-spectrum antibiotics if absolute neutrophil count falls below 1.0 × 10⁹/L or clinical deterioration occurs. 1

Manage Elevated Uric Acid

• Initiate allopurinol or rasburicase to prevent tumor lysis syndrome, especially given the elevated serum uric acid and likelihood of initiating chemotherapy soon. 1
• Ensure aggressive hydration (if cardiac function permits) to maintain urine output and prevent uric acid nephropathy. 1

Complete Staging Workup

Once diagnosis is confirmed, the following must be completed before treatment initiation:

• CT scan of neck, chest, abdomen, and pelvis is mandatory for volumetric assessment and identification of bulky disease (mediastinal mass >1/3 maximum horizontal thoracic diameter). 1, 4
• FDG-PET scan is strongly recommended for accurate staging and baseline assessment, as it will be critical for response evaluation. 1
• Cardiac and pulmonary function testing (echocardiogram or MUGA scan, pulmonary function tests) to identify patients at increased risk of treatment-related complications, particularly given the planned use of doxorubicin and bleomycin in ABVD. 1, 4
• Hepatitis B, hepatitis C, and HIV screening is mandatory before chemotherapy initiation. 4

Critical Pitfall to Avoid

Do not initiate chemotherapy based solely on bone marrow findings without lymph node confirmation. 1 The megaloblastoid changes and hypersegmented neutrophils suggest a concurrent nutritional deficiency (B12/folate), which must be evaluated and addressed. Starting chemotherapy in a patient with severe pancytopenia from multiple causes (lymphoma infiltration, nutritional deficiency, possible autoimmune component given splenomegaly) without full characterization significantly increases treatment-related mortality. 1, 3

Addressing the Pancytopenia Etiology

The combination of:

• Normocytic normochromic anemia with macro-ovalocytes and hypersegmented neutrophils
• Bone marrow erythroid hyperplasia with megaloblastoid changes
• Evolving pancytopenia

Suggests multiple contributing factors beyond lymphoma alone:

• Check vitamin B12 and folate levels immediately, as deficiency can coexist with lymphoproliferative disorders and significantly worsen pancytopenia. 3
• Evaluate for autoimmune cytopenias (direct antiglobulin test, antiplatelet antibodies) as autoimmune hemolytic anemia and immune thrombocytopenia can occur with Hodgkin lymphoma, though rare (0.19-0.29% at presentation). 5, 6
• Consider the anemia of chronic disease related to IL-6 elevation and hepcidin dysregulation, which is common in Hodgkin lymphoma and causes iron restriction. 3

Treatment Timing Considerations

Once diagnosis is confirmed and staging completed, treatment should not be delayed if the patient remains clinically stable with supportive care. 2, 7 However, if absolute neutrophil count drops below 0.5 × 10⁹/L or active infection develops, infection control takes precedence before initiating myelosuppressive chemotherapy. 1

For advanced-stage disease (likely given bone marrow involvement), the standard treatment will be 6-8 cycles of ABVD chemotherapy. 1, 4 The severe baseline pancytopenia may require dose modifications or growth factor support, but this should be determined after full diagnostic workup is complete.

Fertility Preservation

Reproductive counseling must be offered immediately before any treatment initiation, as chemotherapy and radiotherapy cause permanent fertility damage. 1, 4 Sperm banking or ovarian tissue preservation should be arranged urgently if the patient desires future fertility, as treatment cannot be delayed indefinitely.