Mechanisms of Hypercalcemia in Non-Hodgkin Lymphoma and Associated Outcomes: A Retrospective Review

Clin Lymphoma Myeloma Leuk. 2018 Feb;18(2):e123-e129. doi: 10.1016/j.clml.2017.12.006. Epub 2017 Dec 30.

Abstract

Introduction: The etiology of hypercalcemia in non-Hodgkin lymphoma (NHL) has been most often attributed to either elevated serum levels of 1,25-dihydroxycholecalciferol (calcitriol) or parathyroid-related protein (PTHrP). In a single-center retrospective review, we evaluated the incidence of, and outcomes associated with, hypercalcemia in NHL.

Patients and methods: The medical records of patients with a histologically confirmed diagnosis of NHL and ≥ 1 episode of hypercalcemia were evaluated for demographic and lymphoma-specific factors, including the response to therapy and overall survival.

Results: Fifty-four patients with NHL met the inclusion criteria. Most patients (57.4%) had diffuse large B-cell lymphoma, of which, 70% were the nongerminal center subtype. Approximately one half (42.6%) of the included patients had undergone serologic investigation into the etiology of hypercalcemia; however, only 17 patients (31.5%) had both a serum PTHrP and a calcitriol level properly collected. Of the 17 cases for which both a serum calcitriol and a PTHrP were collected, most (61.1%) were found to have neither an elevation of serum calcitriol nor an elevation of PTHrP. The degree of calcitriol elevation correlated with worse progression-free survival (P = .04) but not overall survival.

Conclusion: The major mechanism by which NHL patients develop hypercalcemia is not mediated by calcitriol or PTHrP. Hypercalcemia is most prevalent in patients with diffuse large B-cell lymphoma of the nongerminal cell subtype. Patients with calcitriol-mediated hypercalcemia showed a trend toward worse outcomes, suggesting that calcitriol might be a marker of high-grade lymphoma, transformation to such, or a surrogate for more advanced disease.

Keywords: Calcitriol; NHL; PTHrP; Survival.

MeSH terms

  • Calcitriol / blood*
  • Female
  • Humans
  • Hypercalcemia / blood*
  • Hypercalcemia / etiology
  • Kaplan-Meier Estimate
  • Lymphoma, Large B-Cell, Diffuse / blood
  • Lymphoma, Large B-Cell, Diffuse / complications
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Lymphoma, Non-Hodgkin / blood*
  • Lymphoma, Non-Hodgkin / complications
  • Lymphoma, Non-Hodgkin / therapy
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Parathyroid Hormone-Related Protein / blood*
  • Retrospective Studies

Substances

  • Parathyroid Hormone-Related Protein
  • Calcitriol