Relapsed Chronic Lymphocytic Leukemia Heralded by Parathyroid Hormone Related Peptide-Mediated Hypercalcemia

Hypercalcemia is a common, serious complication in patients with malignancy and is associated with significant morbidity. Compared to patients with solid tumor malignancies, the reported incidence of hypercalcemia in patients with indolent lymphoid malignancies is lower and rare in those with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). In this report, we describe the case of a patient with a history of CLL/SLL previously treated with multiple lines of therapy and thought to be in remission who presented with symptomatic, severe hypercalcemia. Her calcium initially improved; however, it increased after discontinuation of steroids despite aggressive fluid resuscitation, calcitonin, and bisphosphonate therapy. Following an extensive laboratory and radiographic evaluation, her hypercalcemia was concluded to be secondary to elevation in serum parathyroid hormone-related peptide in the setting of recurrent CLL/SLL. Notably, the patient had no evidence of Richter transformation and initially responded well to steroids, denosumab, and CLL-directed therapy; however, she later had refractory CLL/SLL and hypercalcemia. Hematologic malignancy, including CLL/SLL, could be considered in the differential diagnosis of hypercalcemia and can be present either at the time of initial diagnosis or signal disease relapse in the appropriate context.