Vitamin D levels and their associations with survival and major disease outcomes in a large cohort of patients with chronic graft-vs-host disease

Mašenjka Katić, Filip Pirsl, Seth M Steinberg, Marnie Dobbin, Lauren M Curtis, Dražen Pulanić, Lana Desnica, Irina Titarenko, Steven Z Pavletic, Mašenjka Katić, Filip Pirsl, Seth M Steinberg, Marnie Dobbin, Lauren M Curtis, Dražen Pulanić, Lana Desnica, Irina Titarenko, Steven Z Pavletic

Abstract

Aim: To identify the factors associated with vitamin D status in patients with chronic graft-vs-host disease (cGVHD) and evaluate the association between serum vitamin D (25(OH)D) levels and cGVHD characteristics and clinical outcomes defined by the National Institutes of Health (NIH) criteria.

Methods: 310 cGVHD patients enrolled in the NIH cGVHD natural history study (clinicaltrials.gov: NCT00092235) were analyzed. Univariate analysis and multiple logistic regression were used to determine the associations between various parameters and 25(OH)D levels, dichotomized into categorical variables: ≤20 and >20 ng/mL, and as a continuous parameter. Multiple logistic regression was used to develop a predictive model for low vitamin D. Survival analysis and association between cGVHD outcomes and 25(OH)D as a continuous as well as categorical variable: ≤20 and >20 ng/mL; <50 and ≥50 ng/mL, and among three ordered categories: ≤20, 20-50, and ≥50 ng/mL, was performed.

Results: 69 patients (22.3%) had serum 25(OH)D ≤20 ng/mL. Univariate analysis showed that supplement intake, nutritional status (severely malnourished, moderately malnourished, well-nourished), race (African-American, other), and estimated creatinine clearance (eCCr) were associated with 25(OH)D levels. A predictive model was developed based on supplement intake, nutritional status, race, and eCCr, accurately predicting 77.9% of patients with 25(OH)D ≤20 and 65.2% of those with 25(OH)D >20 ng/mL. No association was found between vitamin D and major cGVHD characteristics, but patients with 25(OH)D ≤20 ng/mL had somewhat decreased survival.

Conclusion: Nutritional status and adequate supplementation are important to maintain 25(OH)D >20 ng/mL in cGVHD patients. Intervention studies and more research is needed to reveal the underlying mechanism of vitamin D metabolism in cGVHD setting.

Figures

Figure 1
Figure 1
Survival analysis for vitamin D in chronic graft-vs-host disease (cGVHD). Patients with serum 25(OH)D≤20 ng/mL had somewhat poorer survival than patients with serum 25(OH)D>20 ng/mL (P = 0.042).
Figure 2
Figure 2
Survival analysis for vitamin D in groups of chronic graft-vs-host disease (cGVHD) patients stratified by serum level of 25(OH)D≤20 vs 20-50 vs ≥50 ng/mL. Patients with 25(OH)D≤20 ng/mL had somewhat poorer survival than patients with 25(OH)D≥50 ng/mL (P = 0.040), but no difference in survival was found between groups with serum 25(OH)D in a range of 20-50 ng/mL and those with ≥50 ng/mL

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