Case Presentation: : Elderly Patient With Lower-Risk Myelodysplastic Syndrome Without Ring Sideroblasts

Aditi Shastri, MD, Montefiore Einstein Comprehensive Cancer Center, New York, New York, provides background on an elderly patient with lower-risk, ringed sideroblastic negative myelodysplastic syndrome (MDS).

In this case, the patient is an 85-year-old woman who lived alone and had hypertension, hyperlipidemia and depression. She was sent to the treating hematologist from her primary care physician with transfusion-dependent anemia. The patient presented with mild thrombocytopenia and normal white blood cell counts.

She had an extensive anemia workup to rule out nutritional causes of anemia, such as iron deficiency, B12, or folate. They used a serum protein electrophoresis test and evaluated her for micronutrient deficiencies like copper as well as performed did an autoimmune workup. Multiple causes of anemia were ruled out. The patient was slowly becoming transfusion-dependent, requiring 1 unit of packed red blood cells every 2 weeks. A bone marrow aspiration and biopsy, next-generation-sequencing profile, cytogenetic check, and fluorescence in situ hybridization (FISH) panel were completed.

Results demonstrated the patient had a slightly hypercellular marrow with myeloid hyperplasia, abnormal megakaryocytes, reduced erythroid progenitors, and 1% blasts on the bone marrow biopsy. Her cytogenetics did show a loss of the X chromosome, which can happen as people age. The next generation sequencing profile demonstrated a mutation in the splicing factor U2AF1 with a 33% variant allele frequency and a BCOR mutation with 11% variant allele frequency. She was diagnosed with low-risk MDS, with a non-ringed sideroblastic subtype.

She started on subcutaneous injections of erythropoietin at 40,000 units weekly. After 8 weeks or so, she started having a good response to therapy and became transfusion-independent. She had a sustained response for 8 months. However, at the end of this period, she became transfusion-dependent again, this time worse, requiring 1 unit of PRBCs per week. However, her platelet counts continued to stay low in a range of 100,000 to 140,000 [platelets per microliter of blood]. She began on luspatercept and had a sustained response to therapy after 4 months of treatment. This response was well-sustained until early 2024, with some side effects related to therapy. She had grade 1 fatigue. She had some worsening of her hypertension, which required adjustment of her anti-hypertensive medication.

At this point the patient lost response to therapy. She had now lost response to erythropoietin as well as luspatercept treatment. A bone marrow biopsy continued to show this hypercellular marrow with myeloid predominant disease, more dysplastic megakaryocytes than before, but no significant increase in blasts. She continued to have reduced erythroid progenitors.

This patient case is of interest as it is important to note that 75% of patients seen in this clinical practice with lower-risk MDS are ring-sideroblastic-negative and are vulnerable to poor clinical outcomes.