Case 1 Discussion: High-Risk MDS with TP53 Mutation

This case-based discussion illustrates the practical management of a 72-year-old patient with high-risk MDS and TP53 mutation. The patient has significant cytopenias (hemoglobin of 8.2 g/dL, platelets 45 ×10⁹/L, and ANC 0.8 ×10⁹/L) requiring regular transfusions. Despite comorbidities such as coronary artery disease and chronic renal insufficiency, he maintains good functional status (ECOG 1) and desires to minimize clinic visits due to his busy schedule, while a transplant evaluation is ongoing.

The patient prefers limited infusions, highlighting the tension between effective treatment and quality-of-life considerations. Dr. Fazal explains that even in patients with TP53 mutations, allogeneic stem cell transplant remains a potential curative option, supported by trials showing survival advantages in patients up to age 75 years. In the meantime, oral HMAs, such as oral decitabine, can be initiated safely while transplant evaluation is ongoing. He references data suggesting oral HMAs may offer comparable outcomes to intravenous therapy, providing confidence in using oral therapy without compromising eligibility for transplant.

NP Granato discusses the importance of aligning therapy with patient preferences. Oral HMAs can reduce “time toxicity” by limiting infusion visits but do not eliminate the need for monitoring, frequent labs, and supportive care. She emphasizes patient education on adherence, medication reconciliation, and communication about supplements or additional medications that could interfere with treatment. The overall approach underscores a team-based model in which clinicians, nurses, and the patient work collaboratively to optimize both clinical outcomes and quality of life.

Oral HMAs can provide flexibility in high-risk MDS care, balancing efficacy, safety, and patient-centered goals, especially in patients with challenging genetic profiles such as TP53 mutations.