The Role Of Vitamin D In Pediatric Hematopoietic Stem Cell Transplantation

Gathering evidence suggest that sufficient vitamin D levels are beneficial for patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Vitamin D deficiency seems common in the pediatric population, especially in children undergoing treatment for hematologic malignancies. In the present study we followed 123 pediatric patients for up to eight years post-HSCT with the main objective to evaluate the clinical importance of vitamin D status in children following HSCT.

The patients underwent HSCT at our center mostly due to hematologic malignancies, but patients with non-malignant conditions and primary immunodeficiency disorders were also included. Procedures and conditioning regimens followed international guidelines. Data on each patient were obtained from medical records and included basic parameters, transplant characteristics, outcome parameters, data on vitamin D and immunoglobulin substitution and data on nutritional support.

Patients were divided into two cohorts based on calcidiol (25-OH-vitamin D) level pre-SCT; low level (<50 nM) and sufficient level (≥ 50 nM). The distribution of ethnic origin differed between the groups and patients with insufficient levels were older. No differences in other characteristics were seen between the groups.

Acute GvHD (aGvHD) occurred in almost every other patient with higher frequency in the sufficient level group (47 vs. 29 %). Chronic GvHD (cGvHD) occurred in 17 % of patients with higher frequency of moderate to severe cGvHD in the low level group. Neutrophil granulocyte numbers rose faster during the first 3 months in the sufficient group whereas no such difference was observed during the later follow-up. The number of infections did not significantly differ between the groups. Overall survival in patients with malignant diseases was significantly better in the sufficient level group (87 % vs. 50 %). Graft rejection did not occur in patients with sufficient levels of vitamin D. Relapse was more common among patients in the low level group.

We conclude that vitamin D seems to have a role in the outcome for children undergoing HSCT as hypovitaminosis D was associated with increased risk of death, relapse and cGvHD. At the same time effects on immune reconstitution and risk of infections were not obvious and aGvHD occurred more frequently among patients with sufficient vitamin D levels at baseline. It might be postulated that vitamin D has both inhibiting and stimulatory effects on the immune system. This study is an important step towards understanding the role of micronutrients such as vitamin D in pediatric HSCT.