What is the appropriate work-up and management for a patient with myelodysplastic syndrome (MDS) presenting with pancytopenia and fever?

Management of MDS Patients with Pancytopenia and Fever

Rapid initiation of broad-spectrum antibiotics is mandatory in MDS patients presenting with fever and pancytopenia, as this represents a medical emergency requiring immediate intervention. 1

Initial Workup

When evaluating an MDS patient with pancytopenia and fever, the following diagnostic workup should be performed:

1. Complete blood count with differential - Document the severity of pancytopenia
2. Blood cultures (at least two sets from different sites)
3. Chest radiograph - To evaluate for pneumonia (most common infection in MDS)
4. Urinalysis and urine culture
5. Comprehensive metabolic panel
6. Bone marrow aspiration and biopsy with:
   • Cytogenetic analysis
   • Cultures for bacteria, fungi, and mycobacteria
   • Assessment for disease progression/transformation

Management Algorithm

Immediate Management

1. Initiate broad-spectrum antibiotics immediately without waiting for culture results 1

   • Coverage should include Pseudomonas and other gram-negative organisms
   • Consider adding coverage for gram-positive organisms if clinically indicated

2. Supportive care

   • RBC transfusions to maintain hemoglobin >8 g/dL (or higher with comorbidities)
   • Platelet transfusions if <10,000/μL or bleeding
   • Consider short-term G-CSF during severe infection in neutropenic patients 1

Specific Management Based on MDS Risk Category

Lower-Risk MDS (IPSS-R very low, low, or some intermediate)

• Continue broad-spectrum antibiotics until resolution of fever and neutropenia
• Short-term G-CSF may be beneficial during severe infections 1
• Avoid prophylactic antibiotics or G-CSF when not actively infected 1
• Consider disease-modifying therapy based on cytogenetics:
  • For del(5q): Lenalidomide (monitor for worsening cytopenias) 1, 2
  • For non-del(5q): Erythropoiesis-stimulating agents ± G-CSF 1

Higher-Risk MDS

• More aggressive infection management required
• Consider azacitidine if approved and patient is eligible 1
• Evaluate for allogeneic stem cell transplantation if patient is a candidate

Causes of Fever in MDS with Pancytopenia

1. Bacterial infections (most common) 3, 4, 5

   • Pneumonia (most frequent site)
   • Bloodstream infections
   • Urinary tract infections
   • Skin/soft tissue infections

2. Fungal infections (less common but serious)

   • More likely in higher-risk MDS with prolonged neutropenia
   • Consider in patients not responding to antibacterial therapy

3. Atypical infections

   • Nontuberculous mycobacteria can cause disseminated infection in MDS 6
   • Consider if persistent fever despite broad-spectrum antibiotics

4. Non-infectious causes

   • Disease progression/transformation
   • Medication reactions
   • Hemophagocytic syndrome (rare)

Important Considerations and Pitfalls

• Do not delay antibiotic therapy while awaiting culture results in febrile neutropenic MDS patients
• Avoid prophylactic antibiotics in non-febrile MDS patients as they have not shown survival benefit 1
• Monitor for disease progression as worsening pancytopenia may indicate transformation to acute leukemia
• Consider unusual pathogens in patients with persistent fever despite appropriate antibiotics
• Recognize that neutrophil dysfunction in MDS contributes to infection risk even without severe neutropenia 3, 4
• Transfusion support should be individualized based on symptoms and comorbidities, not just laboratory values

Long-term Management

• Regular monitoring of blood counts to detect worsening cytopenias
• Bone marrow examination triggered by worsening cytopenias or appearance of circulating blasts 1
• Consider iron chelation in patients receiving multiple transfusions, especially transplant candidates 1
• Psychosocial support and contact with patient support groups 1

The management of MDS patients with pancytopenia and fever requires prompt recognition and aggressive intervention to prevent serious complications and improve outcomes.