Blood consult Blood consult: treating del(5q) myelodysplastic syndromes

A 58-year-old man with a past medical history of underlying congenital aortic valve defect and hypertension was incidentally diagnosed with an isolated anemia (hemoglobin of 7.8 g/dL) when he presented to his cardiologist with symptoms of fatigue and exertional dyspnea. Evaluation for common causes of anemia, including assessment of serum creatinine, vitamin B12, folate, and iron levels, and evaluation of the gastrointestinal tract with a colonoscopy and esophagogastroduodenoscopy, were all normal. The patient was referred to a hematologist, and a bone marrow biopsy and aspirate demonstrated a normocellular marrow with trilineage hematopoeisis, increased number of megakaryocytes with dysmegakaryopoiesis, and 3% myeloblasts. Cytogenetic analysis revealed a normal karyotype with an isolated deletion 5q [del(5)(q22q35)] abnormality in 20 of 20 metaphase chromosomes, consistent with del (5q) myelodysplastic syndrome (MDS) according to the World Health Organization classification. He had an International Prognostic Scoring System (IPSS) score of 0 and was treated with recombinant humanized erythropoietin at a dose of 60 000 units weekly. He had a hematologic improvement, with a rise in hemoglobin of 3 g/dL, but lost his response 15 months later, at which time he started requiring packed red blood cell transfusions, progressing to 2 units every 2 to 3 weeks despite an increase in the dose of recombinant humanized erythropoietin by 25%. Three-and-a-half years after his MDS diagnosis, he was referred to the Cleveland Clinic. At presentation to our institution, his peripheral blood counts showed a white blood cell count of 2300/mm3, absolute neutrophil count (ANC) of 1120/mm3, normal differential hemoglobin of 7.6 g/dL, mean corpuscular volume of 90.2 fL, and a platelet count of 428 000/mm3. A repeat bone marrow biopsy and aspirate revealed a markedly hypocellular marrow (10%), decreased granulopoiesis and erythropoiesis with dyserythropoietic cells, absence of ring sideroblasts, increased megakaryocytes with dysplastic morphology consisting of predominantly monolobate and occasional hyperlobate forms, and 2% myeloblasts. Cytogenetic analysis showed the previous del(5)(q22q35) abnormal karyotype. His IPSS score was 0.5. He was started on 10 mg of lenalidomide daily but had to be dose-reduced to 5 mg daily after the first cycle because of a drop in ANC (to 340/mm3) and platelets (to 64 000/mm3). Six weeks after starting treatment, his counts started improving; and by 12 weeks, his hemoglobin normalized to 13 to 15 g/dL and his platelet counts stabilized in the range of 120 000 to 150 000/mm3, with an ANC that fluctuated between 1200 and 1500/mm3. A follow-up bone marrow biopsy 6 months later confirmed complete morphologic, but continued, presence of del (5q) clone in 19 of 20 metaphases. His response was sustained for 2.5 years, during which time the patient remained transfusion independent, in excellent physical health, and without any significant treatment-related adverse events. However, the patient then reported worsening fatigue interfering with his daily functioning, and his peripheral blood counts showed significant changes, with a drop in hemoglobin to 8 g/dL, decline in ANC to 660/mm3, and a drop in platelets to 56 000/mm3. A bone marrow examination showed dysplastic morphology involving all 3 lineages with 7% blasts, persistent del(5q) abnormality, and a new, separate 7 clone, indicating disease progression to refractory anemia with excess blasts and an IPSS score of 2.0. He was started on DNA hypomethylating therapy with azacitidine, and elected for an umbilical cord blood transplantation, which unfortunately was not successful. The patient died 7 years after his MDS diagnosis.