An 84-year-old white male was referred to us for anemia and thrombocytosis. He had a history of hypertension and dyslipidemia, for which he took enalapril and lovastatin. He lived and worked on a ranch in far west Texas. He had been fatigued for a few months. Physical exam showed mild conjunctival pallor. Liver and spleen were not palpable. Rest of the physical exam was unremarkable. Complete blood count (CBC) showed a white blood cell count of 9600/microl (4000-10,000) with a normal differential, hemoglobin of 9.9 g/dl (13.5-17.5) with MCV (mean corpuscular volume) of 108 fl (80-95). Platelet count was 986,000/microl (150,000--450,000). Peripheral blood smear showed macrocytosis, moderate anisopoikilocytosis and marked increase in platelets. Prothrombin time and activated partial thromboplastin time were normal. He then underwent a bone marrow biopsy and aspirate. This showed a cellularity of 50%. Megakaryocytes were increased (Fig. 1). Myeloid erythroid ratio was normal. There was no increase in fibrosis. Blasts were 1-2%. Iron stain showed 15-20% ring sideroblasts (Fig. 2). Cytogenetic studies showed a deletion of the long arm of chromosome 5 in all twenty metaphases analyzed. Eleven of those cells also had a deletion of the long arm of chromosome 20 (Fig. 3). Molecular studies did not show JAK2 mutation or BCR/ABL rearrangement. A CALR exon 9, frame shift mutation (c1103_1130del37) was detected.
No mutations were detected in CSF3R, SRTBP1, MPL or SF3B genes.
Patient was initially started on hydroxyurea for cytoreduction. Once the results of cytogenetic studies became available, hydroxurea was discontinued and lenalidomide (10 mg) was initiated. After a transient period of worsening anemia, his CBC improved and by 3 months his peripheral blood counts were normal (Fig. 4). Fluorescent in situ hybridization and PCR studies on peripheral blood, performed 6 months after diagnosis, did not detect 5q deletion, 20q deletion or CALR mutation, suggesting molecular remission. At last follow up at 2 years, patient has continued to stay on lenalidomide and has a normal CBC.