Pretreatment Vitamin D Deficiency Is Associated With Impaired Progression-Free and Overall Survival in Hodgkin Lymphoma

J Clin Oncol. 2019 Dec 20;37(36):3528-3537. doi: 10.1200/JCO.19.00985. Epub 2019 Oct 17.


Purpose: Vitamin D deficiency is described as a modifiable risk factor for the incidence of and mortality in many common cancers; however, data in Hodgkin lymphoma (HL) are lacking.

Patients and methods: We thus performed a study measuring pretreatment vitamin D levels in prospectively treated patients with HL and correlated this with clinical outcomes. A total of 351 patients from the German Hodgkin Study Group clinical trials (HD7, HD8, and HD9) were included.

Results: Fifty percent of patients were vitamin D deficient (< 30 nmol/L) before planned chemotherapy. Pretreatment vitamin D deficiency was more common in relapsed/refractory patients than matched relapse-free controls (median baseline vitamin D, 21.4 nmol/L v 35.5 nmol/L; proportion with vitamin D deficiency, 68% v 41%; P < .001). Vitamin D-deficient patients had impaired progression-free survival (10-year difference, 17.6%; 95% CI, 6.9% to 28.4%; hazard ratio, 2.13; 95% CI, 1.84 to 2.48; P < .001) and overall survival (10-year difference, 11.1%; 95% CI, 2.1% to 20.2%; hazard ratio, 1.82; 95% CI, 1.53 to 2.15; P < .001), consistent across trials and treatment groups. We demonstrated that vitamin D status is an independent predictor of outcome and hypothesized that vitamin D status might be important for the chemosensitivity of HL. We subsequently performed experiments supplementing physiologic doses of vitamin D (calcitriol) to cultured HL cell lines and demonstrated increased antiproliferative effects in combination with chemotherapy. In an HL-xenograft animal model, we showed that supplemental vitamin D (dietary supplement, cholecalciferol) improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone.

Conclusion: On the basis of our clinical and preclinical findings, we encourage that vitamin D screening and replacement be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement therapy in HL.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Antineoplastic Agents / pharmacology
  • Calcitriol / pharmacology
  • Case-Control Studies
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Heterografts
  • Hodgkin Disease / complications*
  • Hodgkin Disease / drug therapy*
  • Hodgkin Disease / mortality
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology
  • Progression-Free Survival
  • Treatment Outcome
  • Vitamin D Deficiency / complications*
  • Young Adult


  • Antineoplastic Agents
  • Calcitriol