What is the treatment approach for a patient experiencing a myelodysplastic syndrome (MDS) flare?

Treatment of MDS Flare

For a patient experiencing an acute MDS flare with worsening cytopenias, immediately provide supportive care with RBC transfusions (maintaining hemoglobin ≥8 g/dL, higher if comorbidities present), broad-spectrum antibiotics for any fever or infection, and G-CSF for severe neutropenia during active infection, while simultaneously reassessing disease risk status to determine if escalation to hypomethylating agents or allogeneic stem cell transplantation is warranted. 1

Immediate Supportive Management

Anemia Management

• Transfuse RBC concentrates to maintain hemoglobin at least 8 g/dL, or 9-10 g/dL in patients with cardiovascular comorbidities or poor functional tolerance. 1
• Administer sufficient RBC units over 2-3 days if necessary to increase hemoglobin above 10 g/dL, which limits chronic anemia effects on quality of life. 1
• Monitor for transfusion reactions including fever, hypoxemia, and respiratory distress within 6 hours (transfusion-associated acute lung injury). 2

Infection Management in Neutropenic Flare

• Rapid initiation of broad-spectrum antibiotics is mandatory for any fever or symptoms of infection in neutropenic patients. 1
• G-CSF can be added during severe infections and improves neutropenia in 60-75% of cases, but prolonged prophylactic use has not demonstrated survival impact. 1
• Prophylactic antibiotics are not recommended for asymptomatic neutropenia. 1

Thrombocytopenia Management

• Prophylactic platelet transfusions are generally not used long-term except in patients receiving myelosuppressive drugs. 1
• For severe thrombocytopenia with bleeding, provide platelet transfusions as clinically indicated. 1

Disease Reassessment During Flare

Critical Distinction: Flare vs. Progression

• Myelosuppression and worsening neutropenia may occur more frequently in the first or second treatment cycles and may not necessarily indicate progression of underlying MDS. 3
• Perform complete blood count with platelets and repeat bone marrow examination if there is concern for disease progression to higher-risk MDS or AML transformation. 1
• Reassess IPSS-R risk category, as this determines whether treatment escalation is needed. 1

When to Escalate Treatment

For patients experiencing a flare that represents progression to higher-risk disease (IPSS-R intermediate, high, or very high):

• Azacitidine 75 mg/m² subcutaneously for 7 consecutive days every 28 days is the first-line reference treatment for higher-risk MDS patients not immediately eligible for allogeneic stem cell transplantation. 1, 4
• At least 6 cycles of azacitidine are recommended, as most patients only respond after several courses. 1
• Alternative "5-2-2" regimens (5 days on, 2 days off, 2 days on) are often easier to apply and considered acceptable. 1

For fit patients ≤70 years with higher-risk disease:

• Allogeneic stem cell transplantation should be proposed to all patients without major comorbidities who have a donor, as this is the only potentially curative option. 1, 4
• Azacitidine can be used for 2-6 cycles before transplantation to reduce bone marrow blasts or for logistical reasons. 1

Monitoring During Flare Management

Laboratory Monitoring

• Perform complete blood count with platelets at baseline, prior to each treatment cycle, and as needed to monitor response and toxicity. 3
• Monitor for citrate toxicity (hypocalcemia, hypomagnesemia) if multiple transfusion units are given rapidly. 2
• Reassess hemoglobin and symptoms after each transfusion unit. 2

Dose Modifications for Hypomethylating Agents

If using azacitidine or decitabine during a flare with severe cytopenias:

• Delay subsequent doses for serum creatinine ≥2 mg/dL, liver enzymes or bilirubin ≥2 times upper limit of normal, or active/uncontrolled infection. 3
• For persistent severe myelosuppression, delay dose up to 2 weeks and reduce dose upon restarting therapy. 3

Common Pitfalls to Avoid

• Do not assume worsening cytopenias during early treatment cycles indicate disease progression—this may be treatment-related myelosuppression rather than true disease flare. 3
• Do not withhold G-CSF during active severe infection with neutropenia, even though prophylactic use is not recommended. 1
• Do not delay broad-spectrum antibiotics in febrile neutropenic patients—this is mandatory regardless of whether the flare represents disease progression. 1
• Do not transfuse to arbitrary hemoglobin targets without considering patient symptoms and comorbidities—individualize thresholds between 8-10 g/dL based on clinical status. 1