Low Serum Vitamin D Levels Are Associated with Inferior Survival in Follicular Lymphoma: A Prospective Evaluation in SWOG and Lysa Studies.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2712-2712
Author(s):  
Jennifer L. Kelly ◽  
Gilles Salles ◽  
Bryan H. Goldman ◽  
Richard I Fisher ◽  
Olivier Casasnovas ◽  
...  
Keyword(s):  
Vitamin D ◽  
Follicular Lymphoma ◽  
Prognostic Significance ◽  
Serum Vitamin ◽  
B Cell Lymphoma ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
Pre Treatment ◽  
Anti Cd20

Abstract Abstract 2712 Introduction: While follicular lymphoma (FL) prognosis is known to be influenced by clinical characteristics and age, investigation of modifiable factors in the modern treatment era with prognostic significance has been limited. Binding of the active vitamin D metabolite to the nuclear vitamin D receptor results in autocrine and paracrine effects possibly relevant to both cancer prevention and prognosis, including regulation of cell proliferation, induction of apoptosis and differentiation, and immune modulation. Recent literature reports a potential association between high vitamin D and improved prognosis in multiple myeloma, breast and colorectal cancer, and most recently, diffuse large B cell lymphoma and chronic lymphocytic leukemia. Using stored serum from SWOG and LYSA (formerly GELA) FL trials, we evaluated the impact of pretreatment vitamin D on outcome. Methods: Subjects included in the SWOG cohort were previously untreated FL patients (pts) enrolled on one of three SWOG clinical trials (S9800, S9911, S0016) involving CHOP chemotherapy plus an anti-CD20 antibody (rituximab or I-131 tositumomab, enrolled 1998–2008); enrolled pts with pre-treatment serum stored and available through the SWOG serum banking protocol (S8947) were eligible for this analysis. Subjects included in our second independent cohort were also previously untreated FL pts enrolled on LYSA's PRIMA trial (rituximab plus chemotherapy, randomized to rituximab maintenance versus observation; enrolled 2004–2007), who had pre-treatment serum samples stored and available for serum 25(OH)D analysis. Baseline samples for both cohorts were sent to the Mayo Clinic Medical Laboratories where 25(OH)D2 and 25(OH)D3was measured directly using the gold standard liquid chromatography-tandem mass spectrometry method. Our primary endpoint was progression free survival (PFS), defined as time from date of enrollment (SWOG) or registration (PRIMA) to date of progression or death from any cause. Overall survival (SWOG enrollment/PRIMA registration to date of death from any cause) was also evaluated. Kaplan-Meier survival curves were estimated, and differences in survival time by vitamin D status were assessed using the log-rank test. Results: The SWOG cohort included 183 pts enrolled and treated in centers across the US: 55% male, 96% Caucasian, and 30% age 60 or older. Pts largely had grade 1–2 FL (90%) advanced stage (68% stage IV) FL; only 16% were poor prognosis according to IPI. Median serum 25(OH)D was 31 ng/ml. After median follow-up of 5.4 years, pts with serum 25(OH)D < 20 ng/ml (insufficiency threshold per 2010 Institute of Medicine recommendations) had significantly inferior PFS (HR 2.00, p=0.011) and OS (HR 3.57, p=0.003) as compared to those with higher levels (analyses stratified by treatment trial and adjusted for IPI). The PRIMA subset cohort included pts primarily enrolled and treated in France and Belgium: 55% male, and 39% over age 60. The majority of these pts were high risk (91% Stage III/IV, 46% ≥3 by FLIPI, 34% with B symptoms). Surprisingly, the PRIMA serum 25(OH)D distribution was notably shifted in comparison to the SWOG cohort (median 17 ng/ml). As such, we conducted the analysis in this cohort with serum 25(OH)D dichotomized at both the median (17ng/ml) and first quartile (10 ng/ml). After median follow-up of 4.5 years, pts below the median (25(OH)D <17 ng/ml) that received R-CHOP induction (n=237) had significantly inferior OS (HR 3.8, p=0.02) as compared to those with higher levels. Moreover, when dichotomized at the first quartile (10 ng/ml), PFS and OS were significantly inferior for those with lower values (PFS HR 1.73, p=0.0086; OS HR 2.7, p=0.03). Conclusions: In this international collaborative study of newly diagnosed FL pts uniformly treated with chemotherapy and anti-CD20 therapy, we report a robust association between low vitamin D levels and FL outcomes in two independent cohorts. While the threshold for sufficiency with regard to FL outcomes will need to be further defined, and may vary by population and region, the observed prognostic significance of low vitamin D for FL in this study is surprisingly strong, with OS HRs indicating a magnitude of association at or greater than the individual FLIPI prognostic factors, which we currently rely upon clinically. Moreover, serum vitamin D is the first potentially modifiable factor to be associated with FL survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Low Serum Vitamin D Levels Are Associated With Inferior Survival in Follicular Lymphoma: A Prospective Evaluation in SWOG and LYSA Studies

2015 ◽  
Vol 33 (13) ◽  
pp. 1482-1490 ◽  
Author(s):  
Jennifer L. Kelly ◽  
Gilles Salles ◽  
Bryan Goldman ◽  
Richard I. Fisher ◽  
Pauline Brice ◽  
...  
Keyword(s):  
Vitamin D ◽  
Overall Survival ◽  
Follicular Lymphoma ◽  
Serum Vitamin ◽  
Baseline Serum ◽  
Serum Vitamin D ◽  
Hazard Ratios ◽  
Vitamin D Levels ◽  
The Impact

Purpose Recent literature reports a potential association between high vitamin D and improved lymphoma prognosis. We evaluated the impact of pretreatment vitamin D on follicular lymphoma (FL) outcome. Patients and Methods SWOG participants were previously untreated patients with FL enrolled onto SWOG clinical trials (S9800, S9911, or S0016) involving CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab) between 1998 and 2008. Participants included in our second independent cohort were also previously untreated patients with FL enrolled onto the Lymphoma Study Association (LYSA) PRIMA trial of rituximab plus chemotherapy (randomly assigned to rituximab maintenance v observation) between 2004 and 2007. Using the gold-standard liquid chromatography–tandem mass spectrometry method, 25-hydroxyvitamin D was measured in stored baseline serum samples. The primary end point was progression-free survival (PFS). Results After a median follow-up of 5.4 years, the adjusted PFS and overall survival hazard ratios for the SWOG cohort were 1.97 (95% CI, 1.10 to 3.53) and 4.16 (95% CI, 1.66 to 10.44), respectively, for those who were vitamin D deficient (< 20 ng/mL; 15% of cohort). After a median follow-up of 6.6 years, the adjusted PFS and overall survival hazard ratios for the LYSA cohort were 1.50 (95% CI, 0.93 to 2.42) and 1.92 (95% CI, 0.72 to 5.13), respectively, for those who were vitamin D deficient (< 10 ng/mL; 25% of cohort). Conclusion Although statistical significance was not reached in the LYSA cohort, the consistent estimates of association between low vitamin D levels and FL outcomes in two independent cohorts suggests that serum vitamin D might be the first potentially modifiable factor to be associated with FL survival. Further investigation is needed to determine the effects of vitamin D supplementation in this clinical setting.

Vitamin D, Sun Exposure, and Lymphoma Risk.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1783-1783
Author(s):  
Jennifer L. Kelly ◽  
Jonathan W. Friedberg ◽  
Laura M. Calvi ◽  
Edwin van Wijngaarden ◽  
Susan G. Fisher
Keyword(s):  
Vitamin D ◽  
New York State ◽  
Serum Vitamin ◽  
Sun Exposure ◽  
B Cell Lymphoma ◽  
Vitamin D Insufficiency ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
History Of ◽  
Lymphoma Risk

Abstract While a large number of exogenous and endogenous factors have been examined, the etiology of most lymphoma subtypes remains largely unknown. However, recent research suggests that sunlight exposure is associated with reduced lymphoma risk. As sunlight is our major source of vitamin D, it has been suggested that increases in serum vitamin D are responsible for this association. Extra-renal activation of vitamin D results in autocrine and paracrine effects including: maintaining regulation of cell cycle proliferation, apoptosis induction, and increased cell differentiation signaling. Animal and human studies investigating the association between vitamin D and other cancers have provided support for a protective effect of vitamin D related to malignancy. We conducted a case-control study in western New York State to test the hypothesis that a history of vitamin D insufficiency increases the risk of lymphoma. Between October 2005 and September 2007, we recruited 140 newly diagnosed and previously untreated lymphoma cases and 139 clinic-based controls. Cases and controls were recruited concurrently to account for seasonal variation in vitamin D, and a serum sample and self-administered survey were collected from each subject. Current serum 25(OH)D levels were measured by radioimmunoassay (Heartland Assays Inc., Ames, IA). We used multiple linear regression to obtain quantitative estimates of past (5–10 years ago) serum vitamin D concentrations based on survey data and measured current vitamin D levels. Subsequently, we evaluated the association between estimated past vitamin D insufficiency (25(OH)D &lt; 30 ng/mL) and lymphoma risk with multiple logistic regression, controlling for the effects of age, gender, race, prior skin cancer diagnosis, known family history of lymphoma or other cancer, alcohol use, and BMI. Additionally, we examined the association between self-reported past sun exposure and lymphoma risk. The case population included 89 males (64%), 124 whites (89%), and median age was 60; the control population included 61 males (44%), 123 whites (88%), and median age was 52. Median time between case diagnosis and study participation was 21 days (5 month maximum). Cases presented predominantly with advanced stage (64% Stage III/IV) diffuse large B cell lymphoma (23%) and follicular lymphoma (32%) subtypes, and 30 (21%) cases had documented B symptoms. While serum vitamin D values ranged from 2.5 to 45.6 ng/mL, we were surprised to find that the majority of the study population (74%) was vitamin D insufficient. Those with past vitamin D insufficiency were found to have a slightly lower lymphoma risk (multivariate adjusted odds ratio (OR) = 0.68; 95% confidence interval (CI) = 0.38 – 1.23), but this result was not statistically significant. Self-reported past sunbathing (OR=0.30, 95% CI: 0.11–0.85) and past outdoor occupation (OR=0.49, 95% CI: 0.25–0.96) were statistically significantly associated with reduced lymphoma risk. This study fails to provide evidence to support an important role of vitamin D insufficiency in lymphoma etiology. However, we confirmed the previously reported decrease in lymphoma risk associated with measures of increased sun exposure, thereby supporting the validity of our study data. Moreover, our findings suggest that vitamin D insufficiency may not explain the observed association between sun and lymphoma. In light of both the high prevalence of vitamin D insufficiency and the known risk of excessive chronic sun exposure, further investigation of the risks of vitamin D insufficiency, as well as alternative pathways for the demonstrated inverse associations between sun exposure and lymphoma risk, is warranted.

scholarly journals Serum Vitamin D as a Marker of Impaired Information Processing Speed and Early Disability in Multiple Sclerosis Patients

2021 ◽  
Vol 11 (11) ◽  
pp. 1521
Author(s):  
Eleonora Virgilio ◽  
Domizia Vecchio ◽  
Ilaria Crespi ◽  
Paolo Barbero ◽  
Beatrice Caloni ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Information Processing ◽  
Processing Speed ◽  
Serum Vitamin ◽  
Hypovitaminosis D ◽  
Information Processing Speed ◽  
Serum Vitamin D ◽  
Vitamin D Levels

Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and cognitive impairment (CI) in other neurodegenerative diseases have already been linked. We explored the possible correlation between vitamin D and IPS at diagnosis and early disability at last follow-up in 81 MS patients. At diagnosis, we collected vitamin D levels and performed a Symbol Digit Modalities Test (SDMT). Raw scores were adjusted for age, gender, and educational level. Early disability was evaluated with MS severity score (MSSS) and age-related MSSS (ARMSS). A total of 71 patients (86.58%) showed hypovitaminosis D (19.71 ± 8.76 ng/mL) and 18 patients (21.95%) had CI. Patients with CI showed severe hypovitaminosis D (p = 0.004). No patients with sufficient vitamin D levels had CI. We found a positive correlation between vitamin D levels at diagnosis and (1) SDMT raw and z-score that persisted after correction for sunlight exposure and MRI baseline characteristics, and (2) EDSS, MSSS, and ARMSS after a mean 2 year follow-up. Low vitamin D levels may affect both cognition and early disability in newly diagnosed MS patients.

scholarly journals Treatment With Cholecalciferol Leads to Increase Of Selected Semen Parameters in Young Infertile Males: Results of a 6-month Interventional Study

2021 ◽  
pp. S99-S107
Author(s):  
I. Bartl ◽  
M. Ondrušová ◽  
M. Kužma ◽  
P. Jackuliak ◽  
A. Gažová ◽  
...  
Keyword(s):  
Vitamin D ◽  
Semen Analysis ◽  
Sperm Concentration ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Sperm Parameters ◽  
Semen Parameters ◽  
Serum Vitamin D ◽  
Vitamin D Levels

High incidence of infertility along with low vitamin D levels was detected in otherwise healthy young men. The aim is to observe the effect of vitamin D supplementation on semen parameters as assessed by semen analysis in infertile men. In total, 45 men (mean age 36.6 years) in consecutive order were included, of whom 34 finished the study. Subjects were supplemented by vitamin D (cholecalciferol) 2500 IU/day. Vitamin D levels were assessed by HPLC. Semen analysis was performed strictly following 2010 WHO guidelines. Study periods were baseline and month 6. During follow-up, 20 %, 7.4 %, 22 % and 0.7 % increase in serum vitamin D levels, progressive sperm motility, sperm concentration and sperm morphology, respectively, were observed (all p<0.05). At follow-up end, 9 patients (26 %) reached normal sperm parameters of whom 2 fertilized their partner. There was no correlation between vitamin D and semen parameters observed. This study proves that vitamin D supplementation is possibly a modulator of sperm parameters in vitamin D deficient, otherwise healthy men. Although a direct relationship between vitamin D and sperm parameters was not observed obtaining adequate vitamin D levels could likely play a role in the male factor of infertility.

scholarly journals Vitamin D levels in patients with non-Hodgkin lymphoma/diffuse large B-cell lymphoma, chronic lymphocytic leukemia and multiple myeloma

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052094342
Author(s):  
Vasko Graklanov ◽  
Veselin Popov
Keyword(s):  
Vitamin D ◽  
Cell Lymphoma ◽  
Serum Vitamin ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Newly Diagnosed ◽  
Serum Vitamin D ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Vitamin D Levels

Purpose To investigate serum vitamin D levels in patients newly diagnosed with non-Hodgkin lymphoma/diffuse large B-cell lymphoma (NHL-DLBCL), multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). Patients and methods We measured serum levels of vitamin D by ELISA in 103 patients prior to initiation of treatment, of whom 37 were diagnosed with MM, 32 with CLL and 34 with NHL-DLBCL. Results Suboptimal serum vitamin D levels (<30 ng/mL) were observed in all 103 patients. In 14 patients, serum vitamin D levels were between 20 and 30 ng/mL, while all other patients had vitamin D deficiency (<20 ng/mL). Severe vitamin D deficiency (<10 ng/mL) was observed in 32.3% of NHL-DLBCL patients, 28.1% of CLL patients and 81% of MM patients. Conclusion We observed low serum vitamin D levels in the majority of patients newly diagnosed with NHL-DLBCL, CLL and MM.

Abstract P157: Serum Vitamin D is Not Associated With Risk of Incident Diabetes in African Americans: The Jackson Heart Study

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Jane L Harman ◽  
Haiying Chen ◽  
Michael C Sachs ◽  
Kristin G Hairston ◽  
Sherita H Golden ◽  
...  
Keyword(s):  
Vitamin D ◽  
African Americans ◽  
Serum Vitamin ◽  
Cox Proportional Hazards Model ◽  
Incident Diabetes ◽  
European Ancestry ◽  
Total Serum ◽  
Serum Vitamin D ◽  
Vitamin D Levels

A recent meta-analysis of cohort studies with participants primarily of European ancestry, concluded that the risk of incident diabetes was inversely proportional to serum 25-hydroxy-vitamin D levels (25-OH-D). African Americans have lower levels of vitamin D than European Americans. But, lower levels of vitamin D do not seem to carry the same risk for low bone density or vascular calcification for African Americans. We sought to test the hypothesis that low vitamin D elevates the risk of diabetes in African Americans. During 2001-5, 5301 African American adults in Jackson, MS, were examined and blood samples drawn; mean age was 55±13. Serum 25-OH-D2 and 25-OH-D3 were measured from stored frozen serum; mean total 25-OH-D (25-OH-D2 plus 25-OH-D3) =14.5±6.7ng/ml. A seasonal pattern was evident for 25-OH-D3 but not for 25-OH-D2 levels. A cosinor model adjusted for seasonality of 25-OH-D3; mean annualized concentrations and seasonal amplitude were significantly higher for men and for persons of normal BMI compared to overweight or obese persons. Total 25-OH-D, as the sum of predicted annualized mean 25-OH-D3 and measured 25-OH-D2, was used in subsequent analysis. The analysis evaluated 3363 participants after exclusions for missing serum vitamin D (n=141), prevalent diabetes (n=1152), incomplete ascertainment of diabetes (n=62), or no follow-up (n=725). During a mean follow-up of 7.1 years, there were 584 new cases of diabetes. Using a Cox Proportional Hazards model controlling for age and sex, the risk of incident diabetes was significantly and inversely associated with total serum 25-OH-D; after adding BMI to the model, 25-OH-D was not significantly associated with risk of diabetes (Table 1). Physical activity, smoking, and alcohol use did not predict incident diabetes in any model. In conclusion, we found that in this cohort of African-Americans, with low mean 25-OH-D and a relatively narrow range of 25-OH-D, the risk of incident diabetes was not associated with serum 25-OH-D levels after controlling for sex, age, and BMI.

scholarly journals Laparoscopic Extirpation of Adrenal Gland Ganglioneuroma Incidentally Diagnosed during Evaluation for Patchy Alopecia Areata in an Adolescent Boy

2019 ◽  
Vol 28 (5) ◽  
pp. 485-489
Author(s):  
Zlatan Zvizdic ◽  
Emir Haxhija ◽  
Adisa Chikha ◽  
Emir Milisic ◽  
Asmir Jonuzi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Alopecia Areata ◽  
Serum Vitamin ◽  
Serum Vitamin D ◽  
Vitamin D Levels ◽  
Laboratory Investigations ◽  
Vitamin D Supplements ◽  
The Relationship

Objective: We present a 17-year-old boy with an incidentally diagnosed left adrenal ganglioneuroma during the diagnostic workup of alopecia areata. Clinical Presentation and Intervention: Laboratory investigations revealed vitamin D deficiency. Laparoscopic adrenalectomy was performed and ganglioneuroma was confirmed histologically. At follow-up, the vitamin D supplements improved the vitamin D levels followed by a gradual regression of alopecia areata. However, it recurred 18 months later despite the normal levels of serum vitamin D and no tumor recurrence. Conclusion: Further studies should reveal the relationship between alopecia areata and ganglioneuroma as well as the role of vitamin D in alopecia areata.

Clinical factors correlated with vitamin D deficiency in patients with obesity scheduled for bariatric surgery: A single center experience

2020 ◽  
Vol 90 (3-4) ◽  
pp. 346-352
Author(s):  
Vincenzo Pilone ◽  
Salvatore Tramontano ◽  
Carmen Cutolo ◽  
Federica Marchese ◽  
Antonio Maria Pagano ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Serum Vitamin ◽  
Inverse Correlation ◽  
Model Assessment ◽  
Cross Sectional ◽  
Serum Vitamin D ◽  
Female Sex ◽  
Vitamin D Levels

Abstract. We aim to assess the prevalence of vitamin D deficiency (VDD) in patients scheduled for bariatric surgery (BS), and to identify factors that might be associated with VDD. We conducted a cross-sectional observational study involving all consecutive patients scheduled for BS from 2017 to 2019. The exclusion criteria were missing data for vitamin D levels, intake of vitamin D supplements in the 3 months prior to serum vitamin D determination, and renal insufficiency. A total of 206 patients (mean age and body mass index [BMI] of 34.9 ± 10.7 years, and 44.3 ± 6.99 kg/m2, respectively) met the inclusion criteria and were enrolled for data analysis. VDD (<19.9 ng/mL), severe VDD (<10 ng/mL), and vitamin D insufficiency (20–29.9 ng/mL) were present in 68.8 %, 12.5 %, and 31.2 % of patients, respectively. A significant inverse correlation was found between vitamin D levels and initial BMI, parathyroid hormone, and homeostatic model assessment of insulin resistance (r = −0.280, p < 0.05; r = −0.407, p = 0.038; r = −0.445, p = 0.005), respectively. VDD was significantly more prevalent in patients with higher BMI [−0.413 ± 0.12, CI95 % (−0.659; −0.167), p = 0.006], whereas no significant association between hypertension [−1.005 ± 1.65, CI95 % (−4.338; 2.326), p = 0.001], and diabetes type 2 (T2D) [−0.44 ± 2.20, CI95 % (−4.876; 3.986), p = 0.841] was found. We observed significant association between female sex and levels of vitamin D [6.69 ± 2.31, CI95 % (2.06; 11.33), p = 0.006]. The present study shows that in patients scheduled for BS, VDD deficiency is common and was associated with higher BMI, and female sex.

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