A 54-year-old man presented with night sweats and bleeding mouth sores. On routine laboratory testing, he was found to have anemia (hemoglobin 9.4 g/dL, mean corpuscular volume [MCV] 84.9 fL) and thrombocytopenia (120 10 3/µ L), and a white blood cell count (WBC) of 3.92 10 3/µ L. Physical examination revealed splenomegaly 16 cm below the left costal margin (27.5 cm by ultrasound). The rest of his physical examination was unremarkable. Additional hematologic work-up included a bone marrow (BM) biopsy revealing hypercellular marrow (80%) with markedly atypical megakaryocytes, and extensive BM fibrosis on reticulin and trichrome staining. Metaphase cytogenetics was non-evaluable. Fluorescence in situ hybridization for myelodysplastic syndrome (MDS)-associated abnormalities showed deletions of the long arms of chromosomes 7 and 20, and a JAK2V617F mutation was detected by polymerase chain reaction (PCR). Molecular sequencing also revealed an ASXL1 mutation, a poor prognostic marker in some patients with myelofibrosis (MF); however, TET2, IDH1/2 and DNMT3A genes were unmutated. With these findings, he was diagnosed with primary myelofibrosis (PMF). The disease was high risk as per dynamic and standard international prognostic scoring system (IPSS) scores. Shortly after diagnosis, he became red blood cell (RBC) and platelet (PLT) transfusion-dependent. A search for sibling and unrelated donors for allogeneic hematopoietic stem cell transplant was unsuccessful. The patient was started on 5-azacitidine 75 mg/m 2 intravenously (IV) once daily for 7 days given every 28 days together with erythropoietin.