Abstract #1393925: An Interesting Case of Bisphosphonate Resistant Hypercalcemia in Acute Myelogenous Leukemia (AML)

Abstract

Hypercalcemia of malignancy (HCM), a PTH-independent process, usually occurs in solid tumors, multiple myeloma, and occasionally lymphomas. It generally results from excess secretion of parathyroid hormone related protein (PTHrP) by the tumor, osteolytic metastases, or rarely, tumor production of 1,25-(OH)2 vitamin D. We present an unusual case of HCM in a patient with refractory acute myelogenous leukemia (AML) without a defined mechanism that was resistant to bisphosphonate therapy. A 49-year-old woman with refractory AML presented acutely with altered mental status, decreased appetite, nausea, and fatigue. She was found to have HCM with a low intact parathyroid hormone (PTH) level. Her PTHrP and 25-(OH) vitamin D levels were normal, and her 1,25-(OH)2 vitamin D level was suppressed. Other labs were unrevealing, and imaging showed no new osseous lesions. Her hypercalcemia was treated with normal saline, intravenous furosemide, calcitonin, and two doses of pamidronate. Her calcium level normalized but then rebounded and remained elevated despite pamidronate therapy. Denosumab was considered, but due to rapid clinical deterioration, the patient’s family pursued comfort care. AML is an extremely rare cause of HCM. This is the eighth reported case of AML-related HCM since 2000 and the first known case with bisphosphonate resistance. Our patient’s HCM was not explained by typical mechanisms. Based on similar cases, one plausible mechanism for our patient's hypercalcemia was upregulation of receptor activator of nuclear factor κB ligand (RANKL) on osteoblasts due to elevated proinflammatory cytokines. RANKL binds to receptor activator of nuclear factor κB (RANK) on osteoclasts to promote their maturation and thus bone resorption. Regarding treatment, several case reports have demonstrated that denosumab can successfully treat bisphosphonate resistant HCM and is a potential therapeutic option.