Acute myelofibrosis and malignant hypercalcemia

A 33 year old man presented with symptoms of one week's duration; he had a serum calcium of 22.5 mg/dl and a markedly hypercellular bone marrow. Despite therapy with saline diuresis, furosemide mithramycin, total parathyroidectomy and corticosteroids, symptomatic hypercalcemia was poorly controlled. Inappropriate serum parathyroid hormone (PTH) levels were found before and after parathyroidectomy whereas assays of the peripheral blood for osteoclast-activating factor and prostaglandin E (PGE2) were negative. An elevated leukocyte alkaline phosphate level, the inability to aspirate marrow, the marked generalized hyperplasia of all hematopoietic marrow elements, the focal accumulations of blastic cells and increasing reticulin fiber formation led to the diagnosis of acute myelofibrosis. A single course of cytosine arabinoside and thioguanine therapy was followed by profound hyperphosphatemia, hypocalcemia and death. The rarity of hypercalcemia with myeloproliferative disorders is documented by a review of the world literature, and the possible mechanism for hypercalcemia in this patient is discussed.