What is the appropriate management for a patient with monocytosis, eosinophilia, and a slightly low red blood cell count?

Management of Monocytosis and Eosinophilia with Borderline Low RBC

Your laboratory findings show absolute monocytosis (9.6%) and eosinophilia (5.4%) with a slightly low RBC count (4.31), which requires systematic evaluation to exclude both reactive causes and hematologic malignancies, particularly chronic myelomonocytic leukemia (CMML) and myeloid neoplasms with eosinophilia.

Initial Diagnostic Approach

History and Physical Examination

• Obtain detailed travel history to endemic areas for parasitic infections (especially Strongyloides and other helminths), as these are the most common identifiable cause of eosinophilia in travelers (19-80% of cases) 1
• Review all medications for drug-induced eosinophilia or monocytosis, as drugs are among the most common non-infectious causes 1
• Assess for infectious diseases including recent viral infections, tuberculosis, and fungal infections that can cause reactive monocytosis 1, 2
• Examine for splenomegaly, lymphadenopathy, and cutaneous lesions which may indicate underlying hematologic malignancy 1, 2
• Screen for allergic conditions (asthma, eczema, hay fever) as these are the most common causes of eosinophilia in non-endemic areas 1

Essential Laboratory Studies

• Complete blood count with manual differential to confirm absolute monocyte count (>1×10⁹/L defines monocytosis) and absolute eosinophil count (>0.5×10⁹/L defines eosinophilia) 1
• Peripheral blood smear examination looking for dysgranulopoiesis, promonocytes, blasts, neutrophil precursors, and eosinophil morphology 1, 2
• Comprehensive metabolic panel, LDH, uric acid, and liver function tests 1
• Serum tryptase and vitamin B12 levels as elevated levels suggest myeloproliferative variants, particularly PDGFRA fusion-associated neoplasms 1

Critical Rule-Out Testing

For Eosinophilia

• Stool examination for ova and parasites (three samples) if any travel or dietary exposure risk exists 1
• Strongyloides serology as this infection can persist lifelong and cause fatal hyperinfection syndrome in immunocompromised patients 1
• Serum IgE levels to evaluate for allergic causes and ABPA 1

For Monocytosis with Eosinophilia

• BCR-ABL1 molecular testing to definitively exclude chronic myeloid leukemia 1, 2
• PDGFRA and PDGFRB rearrangement testing (by FISH or RT-PCR) to exclude myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase fusion genes, as these predict response to imatinib 1
• Conventional cytogenetics to identify clonal abnormalities and exclude t(9;22) and t(5;12) translocations 1, 2

When Bone Marrow Evaluation is Mandatory

Bone marrow aspiration and biopsy with comprehensive testing is required if: 1, 2

• Monocytosis persists for >3 months without identified reactive cause
• Any dysplasia is noted on peripheral smear
• Blasts are present in peripheral blood
• Unexplained cytopenias accompany the monocytosis/eosinophilia
• Eosinophilia ≥1.5×10⁹/L persists for >3 months after excluding/treating infectious causes 1

Bone Marrow Studies Should Include:

• Morphologic assessment for dysplasia, blast percentage (including myeloblasts, monoblasts, promonocytes), and marrow cellularity 1, 2
• Immunohistochemistry for CD117, CD25, tryptase, and reticulin/collagen stains for fibrosis 1
• Flow cytometry to identify aberrant immunophenotypes (abnormal CD13, CD14, CD16, CD33, CD36, CD64 expression, CD34, CD56 overexpression) 1
• Conventional cytogenetics and FISH for TK fusion gene rearrangements 1
• Molecular testing for mutations in TET2, SRSF2, ASXL1, RAS, and JAK2 if CMML is suspected 1, 2

Management Based on Diagnosis

If Reactive Causes Identified

• Treat underlying infection (empirical albendazole 400mg single dose plus ivermectin 200μg/kg single dose for asymptomatic helminth-associated eosinophilia in patients >24 months) 1
• Discontinue offending medications if drug-induced
• Manage allergic conditions appropriately

If CMML Diagnosed (requires persistent monocytosis >1×10⁹/L, no BCR-ABL1, no PDGFRA/PDGFRB rearrangement, <20% blasts, plus dysplasia or clonal abnormality) 1

For myelodysplastic-type CMML (WBC <13×10⁹/L): 2

• <10% bone marrow blasts: supportive care for cytopenias
• ≥10% bone marrow blasts: 5-azacytidine

For myeloproliferative-type CMML (WBC ≥13×10⁹/L): 2

• <10% blasts: hydroxyurea for cytoreduction
• High blast count: polychemotherapy
• Consider allogeneic stem cell transplantation in selected patients

If Myeloid Neoplasm with TK Fusion Gene

• Imatinib is highly effective for PDGFRA and PDGFRB rearrangements 1

If Hypereosinophilia Without Identified Cause

• Refer to hematology if eosinophilia ≥1.5×10⁹/L persists >3 months after excluding infectious causes 1
• Urgent evaluation for end-organ damage (cardiac, pulmonary, neurologic) as hypereosinophilia can cause life-threatening complications 1

Critical Pitfalls to Avoid

• Do not assume eosinophilia is solely allergic if absolute eosinophil count ≥1.5×10⁹/L, as this level is rarely explained by allergy alone 3
• Do not delay Strongyloides testing in anyone with travel history, as this can be fatal if immunosuppression occurs later 1
• Do not skip molecular testing for PDGFRA/PDGFRB in cases with both monocytosis and eosinophilia, as missing these predicts treatment failure with standard therapy 1
• Do not confuse relative and absolute monocytosis—always calculate absolute counts 2
• Do not overlook the need for bone marrow evaluation in persistent unexplained monocytosis, as this is essential for diagnosing CMML 1, 2