Vitamin D deficiency and supplementation in patients with aggressive B-cell lymphomas treated with immunochemotherapy

Cancer Med. 2018 Jan;7(1):270-281. doi: 10.1002/cam4.1166. Epub 2017 Dec 22.

Abstract

Vitamin D deficiency has been reported to be a negative prognostic factor in elderly patients with aggressive B-cell lymphomas. In vitro data suggest that vitamin D supplementation may enhance rituximab-mediated cytotoxicity. We prospectively assessed 25-hydroxyvitamin D [25(OH)D] levels at diagnosis in a cohort of 155 patients with aggressive B-cell lymphomas of whom 128 had diffuse large B-cell lymphoma (DLBCL) not otherwise specified. 25(OH)D levels were deficient (<20 ng/mL) in 105 (67%), insufficient (20-29 ng/mL) in 32 (21%), and normal (≥30 ng/mL) in 18 (12%) patients with a seasonal variation. Patient characteristics associated with lower 25(OH)D levels were poor performance status, overweight, B-symptoms, elevated LDH, lower albumin and hemoglobin levels. As a result of a change in practice pattern, 116 patients received vitamin D3 (cholecalciferol) supplementation that included a loading phase with daily replacement and subsequent maintenance phase with a weekly dose of 25,000 IU until end of treatment. This resulted in a significant increase in 25(OH)D levels, with normalization in 56% of patients. We analyzed the impact of 25(OH)D levels on event-free survival in patients treated with Rituximab-CHOP. 25(OH)D levels below 20 ng/mL at diagnosis and IPI were independently associated with inferior EFS. Moreover, patients with normalized 25(OH)D levels following supplementation showed better EFS than patients with persistently deficient/insufficient 25(OH)D levels. Our study provides the first evidence that achievement of normal 25(OH)D levels after vitamin D3 supplementation is associated with improved outcome in patients with DLBCL and deficient/insufficient 25(OH)D levels when receiving rituximab-based treatment.

Keywords: Aggressive B-cell lymphoma; Vitamin D; prognosis; supplementation.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cholecalciferol / administration & dosage*
  • Cyclophosphamide / therapeutic use
  • Dietary Supplements
  • Disease-Free Survival
  • Doxorubicin / therapeutic use
  • Female
  • Humans
  • Immunotherapy / methods
  • Lymphoma, Large B-Cell, Diffuse / drug therapy*
  • Lymphoma, Large B-Cell, Diffuse / immunology
  • Lymphoma, Large B-Cell, Diffuse / mortality
  • Male
  • Middle Aged
  • Prednisone / therapeutic use
  • Rituximab / therapeutic use*
  • Treatment Outcome
  • Vincristine / therapeutic use
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / drug therapy*
  • Vitamin D Deficiency / immunology

Substances

  • Vitamin D
  • Cholecalciferol
  • Rituximab
  • Vincristine
  • Doxorubicin
  • Cyclophosphamide
  • 25-hydroxyvitamin D
  • Prednisone

Supplementary concepts

  • CHOP protocol