The second patient was a 65-year-old man who originally presented in December of 2014 with fevers, fatigue, thrombocytopenia, anemia, and leukocytosis. Peripheral blood smear revealed blasts with Auer rods, and bone marrow biopsy demonstrated acute promyelocytic leukemia with t(15;17) present. His disease was characterized as high-risk given a white blood cell count of 56.1 x 103/uL. The patient initially received ATRA 45 mg/m2/day and ATO 0.15 mg/kg daily but developed symptomatic QT prolongation and proceeded to treatment with idarubicin. His course was complicated by prolonged neutropenia with Pseudomonas bacteremia and Aspergillus pneumonia requiring filgrastim and granulocyte transfusions. Bone marrow biopsy following induction was negative for blast cells with normal molecular pathology and negative FISH testing for the t(15;17) translocation. He received three cycles of consolidation consisting of ATRA with idarubicin, mitoxantrone, and cytarabine followed by maintenance therapy with methotrexate 15 mg weekly, 6-mercaptopurine (6-MP) 50 mg daily, and intermittent ATRA 50 mg bid. One year into maintenance, the patient developed pancytopenia, and methotrexate and 6-MP were stopped. A short time later, he developed intermittent right facial paresthesia. MRI brain was concerning for hypointensity over the cerebellum, reflective of subarachnoid bleeding, and hyperintensity in some regions. Lumbar puncture revealed 78% promyelocytes with cytogenetics from cerebrospinal fluid positive for t(15;17). Bone marrow biopsy showed no evidence of blasts, but the karyotype disclosed a new set of anomalies with monosomy of chromosome 7 and an extra marker chromosome in 18 of 20 cells observed (+mar(18)). There were no marrow cells with t(15;17) by FISH or routine karyotype. Hematologic malignancy sequencing panel noted two mutations in the SET binding protein 1 (SETBP1) with allele frequency 36% and 12%. The patient was treated with intrathecal methotrexate 12 mg and intrathecal cytarabine 100 mg followed by whole brain radiation, 2 Gy x 9 fractions. Repeat bone marrow biopsy one month later revealed no excess blasts by flow cytometry, but the karyotype showed persistent monosomy 7 and an extra marker chromosome in all 20 cells observed (+mar(20)). The patient received systemic chemotherapy consisting of cytarabine 100 mg/m2 x 7 days and daunorubicin 60 mg/m2 followed by allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning of busulfan, fludarabine, and antithymocyte globulin (ATG). Post-bone marrow transplant bone marrow biopsy showed no evidence of disease and full donor chimerism. Repeat MRI brain/orbits showed resolution of previously seen enhancement. The patient is doing well 10 months post-bone marrow transplant.