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

Katić, Mašenjka and Pirsl, Filip and Steinberg, Seth M. and Dobbin, Marnie and Curtis, Lauren M. and Pulanić, Dražen and Desnica, Lana and Titarenko, Irina and Pavletic, Steven Z. (2016) Vitamin D levels and their associations with survival and major disease outcomes in a large cohort of patients with chronic graft-vs-host disease. Croatian Medical Journal, 57 (3). pp. 276-286. ISSN 0353-9504

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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.

Abstract in Croatian

Razine vitamina D i njihova povezanost s preživljenjem i glavnim ishodima bolesti u velikoj skupini pacijenata s kroničnom bolešću presatka protiv domaćina ----- Cilj: Odrediti čimbenike koji su povezani s razinama vitamina D kod pacijenata s kroničnom bolešću presatka protiv domaćina (prema engl. chronic-graft-versus-host disease, cGVHD) i odrediti povezanost između serumskih razina vitamina D (25(OH)D) i obilježja cGVHD i kliničkih ishoda definiranih prema kriterijima Nacionalnih instituta za zdravlje SAD-a (prema engl. National Institutes of Health, NIH). ----- Postupci: Analizirali smo 310 pacijenata s cGVHD uključenih u NIH cGVHD studiju (clinicaltrials.gov: NCT00092235). Koristili smo univarijatnu analizu i multiplu logističku regresiju kako bi utvrdili povezanost između različitih parametara i razina 25(OH)D, dihotomiziranih kao kategorijska varijabla: ≤20 i >20 ng/mL i prikazanih kao kontinuirana varijabla. Multipla logistička regresija služila je razvijanju prediktivnog modela za niske vrijednosti vitamina D. Napravili smo analizu preživljenja i odredili povezanost između cGVHD ishoda i 25(OH)D kao kontinuirane ali i kao kategorijske varijable: ≤20 i >20 ng/mL; <50 i ≥50 ng/mL, i ≤20, 20-50 i ≥50 ng/mL. ----- Rezultati: 69 pacijenata (22,3%) imalo je serumski 25(OH)D ≤20 ng/mL. Univarijatna analiza pokazala je da su s razinama 25(OH)D bili povezani uzimanje dodataka prehrani, nutritivni status (iznimno pothranjen, umjereno pothranjen, dobro uhranjen), rasa (Afroamerikanci, ostali) i procijenjeni klirens kreatinina (prema engl. estimated creatinine clerance, eCCr). Razvili smo prediktivni model utemeljen na uzimanju dodataka prehrani, nutritivnom statusu, rasi i eCCr, koji je točno predvidio 77,9% pacijenata s 25(OH)D ≤20 i 65,2% pacijenata s 25(OH)D >20 ng/mL. Vitamin D nije bio povezan s glavnim obilježjima cGVHD, ali su pacijenti s 25(OH)D ≤20 ng/mL imali ponešto skraćeno preživljenje. ----- Zaključak: Nutritivni status i adekvatni dodaci prehrani važni su za održavanje 25(OH)D >20 ng/mL kod pacijenata s cGVHD. Potrebna su daljnja, posebice intervencijska, istraživanja kako bi se otkrili mehanizmi koji upravljaju metabolizmom vitamina D kod pacijenata s cGVHD.

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