{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T05:23:02Z","timestamp":1792905782273,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Vitamin C (VitC) is a cofactor for TET enzymes involved in DNA demethylation and epigenetic regulation. Mutations in\n TET2<\/jats:italic>\n are common drivers of leukemia. Preclinical studies suggest that VitC may delay leukemia progression. This study aimed to evaluate the biological activity, safety, and clinical impact of oral VitC in patients with clonal cytopenia of undetermined significance (CCUS) or lower risk myeloid malignancies.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n EVITA (Epigenetics, Vitamin C, and Abnormal Hematopoiesis) was a double\u2010blind, randomized, placebo\u2010controlled, phase 2 trial conducted in Denmark and the United States. Adults with CCUS or lower risk myeloid malignancies not receiving anticancer therapy were randomly assigned (1:1) to receive oral VitC (1000 mg\/day) or placebo for 12 months, followed by long\u2010term follow\u2010up. The primary end point was the median clonal growth rate from baseline to end of treatment. EVITA was registered at\n ClinicalTrials.gov<\/jats:ext-link>\n (NCT03682029), and is now completed.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Between November 1, 2017, and September 28, 2022, 109 patients were enrolled (VitC,\n n<\/jats:italic>\n \u00a0=\u00a055; placebo,\n n<\/jats:italic>\n \u00a0=\u00a054). Although the primary end point, median clonal growth rate, did not differ between groups (\u22120.016; 95% CI, \u22120.096 to 0.064;\n p<\/jats:italic>\n \u00a0=\u00a0.70), secondary outcomes included differences in inflammatory cytokine trajectories and fewer serious adverse events in the VitC group versus placebo (18 of 55 [33%] vs. 30 of 53 [57%]). In exploratory analyses, overall survival was significantly longer with VitC (hazard ratio, 0.35; 95% CI, 0.17 to 0.71;\n p<\/jats:italic>\n \u00a0=\u00a0.0025).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n These findings suggest oral VitC as a safe, biologically active intervention in patients with early\u2010stage myeloid malignancies and precursor conditions. A phase 3 trial is warranted.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/cncr.70549","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:01:15Z","timestamp":1789974075000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Oral vitamin C supplementation in patients with clonal cytopenia of undetermined significance or lower\u2010risk myeloid malignancies: Results from EVITA, a phase 2 randomized, placebo\u2010controlled trial"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2104-9201","authenticated-orcid":false,"given":"Stine Ulrik","family":"Mikkelsen","sequence":"first","affiliation":[{"name":"Department of Hematology Copenhagen University Hospital\u2013Rigshospitalet Copenhagen Denmark"},{"name":"Biotech Research and Innovation Centre Department of Health and Medical Sciences University of Copenhagen Copenhagen 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