Hypercalcemia at DLBCL Diagnosis May Be Associated with Adverse Impacts

May 5, 2020
Hannah Slater

Hypercalcemia at diagnosis of diffuse large B-cell lymphoma was found to be strongly correlated with adverse prognostic factors and a short diagnosis-to-treatment interval.

Data published in Hematological Oncology suggested that hypercalcemia at diffuse large B-cell lymphoma (DLBCL) diagnosis is strongly correlated with adverse prognostic factors and a short diagnosis-to-treatment interval. 

Moreover, the adverse impact of hypercalcemia on outcome appears to be closely linked to International Prognostic Index (IPI) parameters, indicating that hypercalcemia is a biomarker of the underlying biological aggressiveness of DLBCL. 

“Although hypercalcemia is a known complication of DLBCL, limited data are available concerning its prevalence and its clinical and prognosis significant in this setting,” the authors wrote. “The aims of the present retrospective study, were, first, to investigate the prevalence of hypercalcemia at diagnosis of de novo DLBCL compared to transformed indolent lymphomas and, second, to explore its clinical significance and prognostic value in de novo DLBCL.” 

Researchers evaluated all consecutive patients with newly diagnosed DLBCL or transformed indolent lymphoma from the University Hospital of Reims between January 2006 and June 2018. For the subsequent analysis on hypercalcemia, primary DLBCL of the central nervous system, post-transplantation lymphoproliferative disorders (PTLD), HIV-associated lymphoma, lymphomatoid granulomatosis, B-cell lymphoma unclassifiable with features intermediate between DLBCL and Hodgkin lymphoma, and transformation of a previously diagnosed indolent lymphoma were excluded. 

For patients who were hypercalcemic, researchers looked for previous granulomatosis or primary hyperparathyroidism (PHPT), thiazide diuretic treatment, and vitamin D supplementation in order to exclude hypercalcemia unrelated to DLBCL. Histological markers including CD10, BCL6, MUM1, BCL2, MYC, EBER, and Ki67 were also collected. Karyotype and results of fluorescence in situ hybridization for MYC, BCL2, and BCL6 were collected if available.

Overall, a total of 305 patients, including 248 with de novo DLBCL and 57 with transformed indolent lymphomas, were assessed. Further, the prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. 

Hypercalcemia in de novo DLBCL was found to be strongly associated with high-risk features, especially with IPI components, but also with B symptoms, β2-micro-globulin, hemoglobin, and albumin levels. The diagnosis-to-treatment interval was also significantly less for hypercalcemic patients (P = 0.001). Moreover, these associations with adverse prognostic factors translated into lower rates of EFS24 (HR, 1.66; 95% CI, 1.08-2.54) and shorter progression-free survival (P = .0059) and overall survival (P = .0003) for patients with lymphoma-related hypercalcemia but not independently of IPI parameters.

“Contrary to popular belief, the prevalence of hypercalcemia does not appear to be higher in transformed indolent lymphomas in our study,” the authors wrote. 

Notably, PTH levels were only available in approximately 1 quarter of the patients with hypercalcemia, and as a result, the diagnosis of PHPT is possibly underestimated in this study cohort. Additionally, the researchers could not explore whether patients with calcitriol-mediated hypercalcemia had worse outcomes than patients with other hypercalcemia mechanisms, as PTH-rp and calcitriol were only available in a small number of cases. 

“This finding encourages us to reconsider our biological evaluation in case of hypercalcemia at diagnosis of DLBCL and would ideally need to be studied prospectively,” the authors wrote.



Gauchy A, Kanagaratnam L, Quinquenel A, et al. Hypercalcemia at diagnosis of diffuse large B-cell lymphoma is not uncommon and is associated with high-risk features and a short diagnosis-to-treatment interval. Hematological Oncology. doi:10.1002/hon.2735.