Parathyroid-hormone-related peptide in hematologic malignancies

Purpose To determine whether parathyroidhormone-related peptide (PTHRP) is an important pathogenetic mediator of hypercalcemia in patients with hematologic malignancies. Patients and methods We conducted a cohort analytic study in 76 consecutive patients with nonHodgkinʹs lymphoma (NHL), Hodgkinʹs disease, multiple myeloma, and Waldenströmʹs macroglobulinemia, 14 of whom were hypercalcemic. Thirty normal subjects served as a control group. Results Using the NH2-terminal radioimmunoassay, PTHRP concentrations in healthy controls were undetectable (<7.5 pmol equivalents of PTHRP [fragment 1–34] per liter). The majority of hypercalcemic patients (8/14) had non-Hodgkinʹs lymphoma, and 62.5% of these (5/8) had significant elevations of circulating PTHRP concentrations (mean 70.5 ± 38.5 pmol equivalents of PTHRP per liter) (P<0.01). In non-Hodgkinʹs lymphoma, 11 of 30 patients with advanced disease (stage IV) had elevated PTHRP concentrations, and of these, 8 of 11 had high-grade pathology. In contrast, only 3 of 21 patients with less advanced disease (stage I to III) had elevated PTHRP concentrations. In 4 NHL patients with elevated PTHRP concentrations sampled prior to cytotoxic chemotherapy, tumor response was associated with a decrease in PTHRP. Concomitant suppression of 1,25(OH)2D3 concentrations was observed in 66% of hypercalcemic patients with non-Hodgkinʹs lymphoma. Conclusions These results suggest that PTHRP may be an important pathogenetic factor in the development of hypercalcemia in hematologic malignancies, notably in non-Hodgkinʹs lymphoma.