{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T23:13:28Z","timestamp":1761174808075,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Vitamin D deficiency has been correlated with various conditions, including the risk of developing lymphoid malignancies. This systematic review aimed to assess the association between vitamin D levels at diagnosis of lymphoid malignancies, patient outcomes, and survival. A systematic review was conducted, encompassing 15 studies published until January 2023, involving 4503 patients, examining the relationship between vitamin D and lymphoid cancers. The median age of the patients was 56.5 years, with a median follow-up duration of approximately 36 months across studies. The overall median vitamin D level at initial measurement was 20.4 ng\/mL, while a &lt;20 ng\/mL threshold was used to define vitamin D insufficiency. The results demonstrated significant associations between vitamin D levels and patient outcomes in several lymphoid malignancies, with a pooled risk in disease progression of 1.93 and a pooled hazard ratio of 2.06 for overall survival in patients with 25-(OH)D levels below the normal threshold of 20 ng\/mL. Among findings, it was demonstrated that supplemental vitamin D improves the chemosensitivity of tumors by reducing the rate of tumor growth compared with vitamin D or chemotherapy alone. Vitamin D had a protective effect for patients with DLBCL under R-CHOP treatment, while vitamin D insufficiency was associated with the impairment of rituximab treatment and showed worse clinical outcomes in chimeric antigen receptor T-cell (CAR-T) recipients. Although one study found no association between vitamin D deficiency and the cause of death, most associated vitamin D insufficiency with early clinical failure and lower survival probability. In conclusion, his systematic review highlights the importance of vitamin D levels in the prognosis and survival of patients with lymphoid malignancies. Further research is needed to better understand the underlying mechanisms and explore the potential benefits of vitamin D supplementation in managing these cancers.<\/jats:p>","DOI":"10.3390\/curroncol30040331","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T05:35:46Z","timestamp":1681968946000},"page":"4351-4364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Systematic Review Assessing the Impact of Vitamin D Levels on Adult Patients with Lymphoid Malignancies"],"prefix":"10.3390","volume":"30","author":[{"given":"Cristina","family":"Potre","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Discipline of Hematology, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ema","family":"Borsi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Discipline of Hematology, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5508-1344","authenticated-orcid":false,"given":"Ovidiu","family":"Potre","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Discipline of Hematology, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6840-9553","authenticated-orcid":false,"given":"Ioana","family":"Ionita","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Discipline of Hematology, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5358-882X","authenticated-orcid":false,"given":"Miruna","family":"Samfireag","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Discipline of Clinical Practical Skills, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5944-3522","authenticated-orcid":false,"given":"Dan","family":"Costachescu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics-Traumatology, Urology, Radiology, and Medical Imaging, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1355-3790","authenticated-orcid":false,"given":"Cristina","family":"Secosan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Discipline of Obstetrics and Gynecology, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Lazar","sequence":"additional","affiliation":[{"name":"Second Department of Internal Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-8068","authenticated-orcid":false,"given":"Anca Irina","family":"Ristescu","sequence":"additional","affiliation":[{"name":"Discipline of Anesthesia and Intensive Care, School of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, University Street 16, 700115 Iasi, Romania"},{"name":"Department of Anesthesia and Intensive Care, Regional Institute of Oncology, General Henri Mathias Berthelot 2-4, 700483 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"678487","DOI":"10.3389\/fimmu.2021.678487","article-title":"20S-Hydroxyvitamin D3, a Secosteroid Produced in Humans, Is Anti-Inflammatory and Inhibits Murine Autoimmune Arthritis","volume":"12","author":"Postlethwaite","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1447-0594.2010.00668.x","article-title":"Vitamin D hormone: A multitude of actions potentially influencing the physical function decline in older persons","volume":"11","author":"Cesari","year":"2011","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1210\/jc.2012-2772","article-title":"Active vitamin D (1,25-dihydroxy vitamin D) and bone health in middle-aged and elderly men: The European Male Aging Study (EMAS)","volume":"98","author":"Vanderschueren","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.ecl.2010.02.007","article-title":"The vitamin D receptor: New paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D(3)","volume":"39","author":"Pike","year":"2010","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ecl.2010.02.011","article-title":"The role of vitamin D in cancer prevention and treatment","volume":"39","author":"Krishnan","year":"2010","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.pbiomolbio.2006.02.014","article-title":"Vitamin D: Its role in cancer prevention and treatment","volume":"92","author":"Holick","year":"2006","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1042\/BJ20110744","article-title":"Vitamin D and cancer: A review of molecular mechanisms","volume":"441","author":"Fleet","year":"2012","journal-title":"Biochem. J."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Negri, M., Gentile, A., de Angelis, C., Mont\u00f2, T., Patalano, R., Colao, A., Pivonello, R., and Pivonello, C. (2020). Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells. Nutrients, 12.","DOI":"10.3390\/nu12061798"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.3390\/nu5103993","article-title":"Molecular link between vitamin D and cancer prevention","volume":"5","author":"Moukayed","year":"2013","journal-title":"Nutrients"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bhoora, S., and Punchoo, R. (2020). Policing Cancer: Vitamin D Arrests the Cell Cycle. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239296"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5020","DOI":"10.3390\/nu7065020","article-title":"Mechanistic Effects of Calcitriol in Cancer Biology","volume":"7","year":"2015","journal-title":"Nutrients"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Asunci\u00f3n, F.B. (2020). Vitamin D Effects on Cell Differentiation and Stemness in Cancer. Cancers, 12.","DOI":"10.3390\/cancers12092413"},{"key":"ref_13","first-page":"1","article-title":"Exploring vitamin D metabolism and function in cancer","volume":"50","author":"Jeon","year":"2015","journal-title":"Exp. Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.leukres.2009.09.010","article-title":"Vitamin D3-driven signals for myeloid cell differentiation\u2014Implications for differentiation therapy","volume":"34","author":"Hughes","year":"2013","journal-title":"Leuk. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Marcinkowska, E. (2022). Vitamin D Derivatives in Acute Myeloid Leukemia: The Matter of Selecting the Right Targets. Nutrients, 14.","DOI":"10.3390\/nu14142851"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Umar, M., Sastry, K.S., and Chouchane, A.I. (2018). Role of Vitamin D Beyond the Skeletal Function: A Review of the Molecular and Clinical Studies. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061618"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1210\/en.2008-1217","article-title":"Inactivation of the human vitamin D receptor by caspase-3","volume":"150","author":"Malloy","year":"2009","journal-title":"Endocrinology"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"El-Sharkawy, A., and Malki, A. (2020). Vitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications. Molecules, 25.","DOI":"10.3390\/molecules25143219"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Irani, M., Seifer, D.B., Grazi, R.V., Irani, S., Rosenwaks, Z., and Tal, R. (2017). Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial. Nutrients, 9.","DOI":"10.3390\/nu9040334"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Roffe-Vazquez, D.N., Huerta-Delgado, A.S., Castillo, E.C., Villarreal-Calder\u00f3n, J.R., Gonzalez-Gil, A.M., Enriquez, C., Garcia-Rivas, G., and Elizondo-Montemayor, L. (2019). Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225811"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"443","DOI":"10.4103\/0019-5413.139827","article-title":"Medical subject headings (MeSH) terms","volume":"48","author":"Dhammi","year":"2014","journal-title":"Indian. J. Orthop."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1080\/02763869.2019.1588072","article-title":"PROSPERO: An International Register of Systematic Review Protocols","volume":"38","author":"Schiavo","year":"2019","journal-title":"Med. Ref. Serv. Q."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"203","DOI":"10.5195\/jmla.2017.88","article-title":"Open Science Framework (OSF)","volume":"105","author":"Foster","year":"2017","journal-title":"J. Med. Libr. Assoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4191","DOI":"10.1200\/JCO.2010.28.6674","article-title":"Vitamin D insufficiency and prognosis in non-Hodgkin\u2019s lymphoma","volume":"28","author":"Drake","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1182\/blood-2010-07-295683","article-title":"Vitamin D insufficiency and prognosis in chronic lymphocytic leukemia","volume":"117","author":"Shanafelt","year":"2011","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s10552-011-9885-6","article-title":"Serum levels of 25-hydroxyvitamin D and survival in Norwegian patients with cancer of breast, colon, lung, and lymphoma: A population-based study","volume":"23","author":"Steinar","year":"2012","journal-title":"Cancer Causes Control"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1179\/1607845412Y.0000000025","article-title":"Prognostic impact of serum 25-hydroxivitamin D [25(OH)D] concentrations in patients with lymphoid malignancies","volume":"18","author":"Aref","year":"2013","journal-title":"Hematology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1200\/JCO.2013.53.4537","article-title":"Vitamin D deficiency impairs rituximab-mediated cellular cytotoxicity and outcome of patients with diffuse large B-cell lymphoma treated with but not without rituximab","volume":"32","author":"Bittenbring","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1200\/JCO.2014.57.5092","article-title":"Low serum vitamin D levels are associated with inferior survival in follicular lymphoma: A prospective evaluation in SWOG and LYSA Studies","volume":"33","author":"Kelly","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e595","DOI":"10.1038\/bcj.2017.70","article-title":"Vitamin D insufficiency is associated with an increased risk of early clinical failure in follicular lymphoma","volume":"7","author":"Tracy","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_32","first-page":"2825","article-title":"25(OH) vitamin D deficiency in lymphoid malignancies, its prevalence and significance. Are We Fully Aware of It?","volume":"26","author":"Bila","year":"2015","journal-title":"Support. Care Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1002\/cam4.1166","article-title":"Vitamin D deficiency and supplementation in patients with aggressive B-cell lymphomas treated with immunochemotherapy","volume":"7","author":"Hohaus","year":"2018","journal-title":"Cancer Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1200\/JCO.19.00985","article-title":"Pretreatment Vitamin D Deficiency Is Associated with Impaired Progression-Free and Overall Survival in Hodgkin Lymphoma","volume":"37","author":"Borchmann","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1007\/s00277-020-04200-5","article-title":"The prognostic value of 25-hydroxy vitamin D deficiency and its interaction with c-Myc expression in diffuse large B cell lymphoma","volume":"99","author":"Wang","year":"2020","journal-title":"Ann. Hematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00432-020-03125-w","article-title":"25-Hydroxy vitamin D deficiency predicts inferior prognosis in mantle cell lymphoma","volume":"146","author":"Xu","year":"2020","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00277-020-04320-y","article-title":"Prognostic value of 25-hydroxy vitamin D in extranodal NK\/T cell lymphoma","volume":"100","author":"Mao","year":"2021","journal-title":"Ann. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.clnu.2020.04.040","article-title":"Bioavailable 25(OH)D level is associated with clinical outcomes of patients with diffuse large B-cell lymphoma: An exploratory study","volume":"40","author":"Chen","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"751e1","DOI":"10.1016\/j.jtct.2022.08.001","article-title":"Vitamin D Insufficiency and Clinical Outcomes with Chimeric Antigen Receptor T-Cell Therapy in Large B-cell Lymphoma","volume":"28","author":"Nath","year":"2022","journal-title":"Transpl. Cell. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Eng. J. Med."},{"key":"ref_41","first-page":"21","article-title":"Associations of 25-hydroxyvitamin D with markers of inflammation, insulin resistance and obesity in black and white community-dwelling adults","volume":"5","author":"Jackson","year":"2016","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3109\/10428194.2013.802314","article-title":"Anemia in diffuse large B-cell non-Hodgkin lymphoma: The role of interleukin-6, hepcidin and erythropoietin","volume":"55","author":"Tisi","year":"2014","journal-title":"Leuk. Lymphoma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"g1903","DOI":"10.1136\/bmj.g1903","article-title":"Vitamin D and risk of cause specificdeath: Systematic review and meta-analysis of observational cohortand randomized intervention studies","volume":"348","author":"Chowdhury","year":"2014","journal-title":"BMJ"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.bone.2013.06.012","article-title":"Calculated free and bioavailable vitamin D metabolite concentrations in vitamin D-deficient hip fracture patients after supplementation with cholecalciferol and ergocalciferol","volume":"56","author":"Glendenning","year":"2013","journal-title":"Bone"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1093\/ajcn\/85.1.6","article-title":"Risk assessment for vitamin D","volume":"85","author":"Hathcock","year":"2007","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1093\/ajcn\/69.5.842","article-title":"Vitamin D supplementation, 25 hydroxy-vitamin D concentrations, and safety","volume":"69","author":"Vieth","year":"1999","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s12937-016-0203-8","article-title":"Appropriate vitamin D loading regimen for patients with advanced lung cancer","volume":"15","author":"Hoffer","year":"2016","journal-title":"Nutr. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e526","DOI":"10.1038\/bcj.2017.9","article-title":"Validation of a vitamin D replacement strategy in vitamin D-insufficient patients with lymphoma or chronic lymphocytic leukemia","volume":"7","author":"Sfeir","year":"2017","journal-title":"Blood Cancer J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.1182\/blood-2013-04-497586","article-title":"Exposure to UV radiation and risk of Hodgkin lymphoma: A pooled analysis","volume":"122","author":"Monnereau","year":"2013","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"332","DOI":"10.3389\/fimmu.2019.00332","article-title":"Antibody-Dependent Cellular Phagocytosis in Antiviral Immune Responses","volume":"10","author":"Tay","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Kusowska, A., Kubacz, M., Krawczyk, M., Slusarczyk, A., Winiarska, M., and Bobrowicz, M. (2022). Molecular Aspects of Resistance to Immunotherapies\u2014Advances in Understanding and Management of Diffuse Large B-Cell Lymphoma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031501"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/30\/4\/331\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:19:42Z","timestamp":1760123982000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/30\/4\/331"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,20]]},"references-count":51,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["curroncol30040331"],"URL":"https:\/\/doi.org\/10.3390\/curroncol30040331","relation":{},"ISSN":["1718-7729"],"issn-type":[{"type":"electronic","value":"1718-7729"}],"subject":[],"published":{"date-parts":[[2023,4,20]]}}}