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Item Langerhans Cell Histiocytosis With Hypothalamic-pituitary and Bone Involvement: A Report of 2 Cases(Oxford University Press, 2025-02-10) Giraldi, Erica A.; Allen, Jason W.; McLemore, Morgan L.; Ioachimescu, Adriana G.; Radiology and Imaging Sciences, School of MedicineCase 1: A 31-year-old woman presented with secondary amenorrhea, polyuria, and polydipsia. Three years later, magnetic resonance imaging of the brain done for headaches found thickening of the pituitary infundibulum. Laboratory evaluation indicated central vasopressin deficiency, mild hyperprolactinemia, and central hypogonadism. Six months later, progression of the infundibular lesion was documented, now contacting the optic chiasm. Biopsy showed epithelioid histiocytes, chronic inflammation, and gliosis. On postoperative scan, a lesion in the parietal calvaria was identified, which was solitary on a bone scan. The patient received cytarabine for 12 months with resolution of infundibular and bone lesion on positron emission tomography-computed tomography scan 1 year later. Case 2: A 23-year-old man presented with polyuria, polydipsia, and unilateral tinnitus. Laboratory evaluation indicated vasopressin deficiency and central hypogonadism. External ear canal biopsy indicated an infiltrative lesion with eosinophils, small lymphocytes and histiocytes. Magnetic resonance of the brain revealed hypothalamic/infundibular and parietal and mastoid bone lesions; no other lesions were identified on positron emission tomography-computed tomography. Patient received cytarabine for 1 year with resolution of lesions, which was maintained during follow-up of 4 years. Although rare, Langerhans cell histiocytosis in adults should be considered in the appropriate clinical scenario. Multidisciplinary treatment is required.Item Safety and Pharmacokinetics of the Antisense Oligonucleotide (ASO) LY2181308 as a Single-Agent or in Combination with Idarubicin and Cytarabine in Patients with Refractory or Relapsed Acute Myeloid Leukemia (AML)(Springer, 2013) Erba, Harry P.; Sayar, Hamid; Juckett, Mark; Lahn, Michael; Andre, Valerie; Callies, Sophie; Schmidt, Shelly; Kadam, Sunil; Brandt, John T.; Van Bockstaele, Dirk; Andreeff, Michael; Medicine, School of MedicineSurvivin is expressed in tumor cells, including acute myeloid leukemia (AML), regulates mitosis, and prevents tumor cell death. The antisense oligonucleotide sodium LY2181308 (LY2181308) inhibits survivin expression and may cause cell cycle arrest and restore apoptosis in AML. In this study, the safety, pharmacokinetics, and pharmacodynamics/efficacy of LY2181308 was examined in AML patients, first in a cohort with monotherapy (n = 8) and then post-amendment in a cohort with the combination of cytarabine and idarubicin treatment (n = 16). LY2181308 was administered with a loading dosage of three consecutive daily infusions of 750 mg followed by weekly intravenous (IV) maintenance doses of 750 mg. Cytarabine 1.5 g/m(2) was administered as a 4-hour IV infusion on Days 3, 4, and 5 of Cycle 1, and idarubicin 12 mg/m(2) was administered as a 30-minute IV infusion on Days 3, 4, and 5 of Cycle 1. Cytarabine and idarubicin were administered on Days 1, 2, and 3 of each subsequent 28-day cycle. Reduction of survivin was evaluated in peripheral blasts and bone marrow. Single-agent LY2181308 was well tolerated and survivin was reduced only in patients with a high survivin expression. In combination with chemotherapy, 4/16 patients had complete responses, 1/16 patients had incomplete responses, and 4/16 patients had cytoreduction. Nine patients died on study: 6 (monotherapy), 3 (combination). LY2181308 alone is well tolerated in patients with AML. In combination with cytarabine and idarubicin, LY2181308 does not appear to cause additional toxicity, and has shown some clinical benefit needing confirmation in future clinical trials.