{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:01:34Z","timestamp":1785438094238,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education and Science of Russia","award":["1026022000066-7"],"award-info":[{"award-number":["1026022000066-7"]}]},{"award":["1026022000066-7"],"award-info":[{"award-number":["1026022000066-7"]}],"id":[{"id":"https:\/\/ror.org\/00ghqgy32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: Diffuse large B-cell lymphoma (DLBCL) with TP53 abnormalities, corresponding to the LymphGen A53 molecular subtype, represents a biologically high-risk group associated with primary resistance to standard R-CHOP therapy. Epigenetic sensitization using hypomethylating agents may enhance chemosensitivity in this setting. We prospectively evaluated the clinical activity and safety of a molecularly adapted DAC-R-CHOP regimen in newly diagnosed A53-DLBCL. Methods: In this single-center prospective pilot cohort study, 70 consecutive patients with newly diagnosed DLBCL underwent targeted next-generation sequencing using a 60-gene panel with integrated copy number variation analysis. Six patients (8.5%) were classified as the A53 subtype. All patients received one cycle of standard R-CHOP. From cycle 2 onward, A53 patients received decitabine (10 mg\/m2 IV, days 1\u20135) prior to R-CHOP (DAC-R-CHOP), for a total of six cycles. The primary endpoint was complete metabolic response (CMR) according to Lugano 2014 criteria. Exact 95% confidence intervals (CI) were calculated. Results: The median age of the A53 cohort was 65 years. CMR was achieved in all six patients (100%; 95% CI, 54\u2013100%). At a median follow-up of 6 months, all patients remained alive in confirmed CMR. Grade III\u2013IV hematologic toxicity occurred in all cases. Febrile neutropenia developed in 100% of patients, requiring mandatory G-CSF support and anti-infective therapy; no treatment-related mortality or permanent dose reductions were observed. Two patients (33%) experienced gastrointestinal bleeding related to local tumor lysis, which was managed conservatively without protocol discontinuation. Conclusions: In this prospective molecularly stratified pilot cohort, integration of decitabine into front-line immunochemotherapy showed promising clinical activity in A53-DLBCL, albeit at the cost of substantial hematologic toxicity requiring intensive supportive care. Given the small sample size, short follow-up, and absence of a comparator arm, these findings should be considered hypothesis-generating and warrant validation in larger multicenter phase II studies with integrated translational biomarker analyses.<\/jats:p>","DOI":"10.3390\/jcm15155844","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"5844","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A53-Adapted Decitabine-Containing R-CHOP in Newly Diagnosed Diffuse Large B-Cell Lymphoma Defined by LymphGen: Preliminary Results of a Prospective Proof-of-Concept Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Marat","family":"Mingalimov","sequence":"first","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"},{"name":"Department of Hematology, I.M. Sechenov First Moscow State Medical University\u2014Ministry of Health of Russia (Sechenov University), Moscow 119991, Russia"},{"name":"N.I. Vavilov Institute of General Genetics, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Baryakh","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"},{"name":"Department of Hematology, I.M. Sechenov First Moscow State Medical University\u2014Ministry of Health of Russia (Sechenov University), Moscow 119991, Russia"},{"name":"N.I. Vavilov Institute of General Genetics, Moscow 119991, Russia"},{"name":"FSBEI FPE \u00abRussian Medical Academy of Continuous Professional Education\u00bb of the Ministry of Healthcare of the Russian Federation, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3468-9115","authenticated-orcid":false,"given":"Polina","family":"Chernova","sequence":"additional","affiliation":[{"name":"Department of Hematology, I.M. Sechenov First Moscow State Medical University\u2014Ministry of Health of Russia (Sechenov University), Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Misyurin","sequence":"additional","affiliation":[{"name":"FSBEI FPE \u00abRussian Medical Academy of Continuous Professional Education\u00bb of the Ministry of Healthcare of the Russian Federation, Moscow 125993, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Misyurina","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"},{"name":"Department of Hematology, I.M. Sechenov First Moscow State Medical University\u2014Ministry of Health of Russia (Sechenov University), Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariia","family":"Orlova","sequence":"additional","affiliation":[{"name":"Department of Hematology, I.M. Sechenov First Moscow State Medical University\u2014Ministry of Health of Russia (Sechenov University), Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Tolstykh","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"},{"name":"Department of Hematology, I.M. Sechenov First Moscow State Medical University\u2014Ministry of Health of Russia (Sechenov University), Moscow 119991, Russia"},{"name":"N.I. Vavilov Institute of General Genetics, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Zotina","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"},{"name":"Department of Hematology, I.M. Sechenov First Moscow State Medical University\u2014Ministry of Health of Russia (Sechenov University), Moscow 119991, Russia"},{"name":"N.I. Vavilov Institute of General Genetics, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliia","family":"Shimanovskaia","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-1640","authenticated-orcid":false,"given":"Tatiana","family":"Chudnova","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"},{"name":"Department of Hematology, I.M. Sechenov First Moscow State Medical University\u2014Ministry of Health of Russia (Sechenov University), Moscow 119991, Russia"},{"name":"N.I. Vavilov Institute of General Genetics, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kochneva","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"},{"name":"Department of Hematology, I.M. Sechenov First Moscow State Medical University\u2014Ministry of Health of Russia (Sechenov University), Moscow 119991, Russia"},{"name":"N.I. Vavilov Institute of General Genetics, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kseniya","family":"Tsurkina","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8480-5505","authenticated-orcid":false,"given":"Dmitry","family":"Lebedev","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgii","family":"Tyshkevich","sequence":"additional","affiliation":[{"name":"FSBI FPE \u00abCentral State Medical Academy\u00bb of the Administrative Department of the President of the Russian Federation, Moscow 121359, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1653-8388","authenticated-orcid":false,"given":"Viktoriia","family":"Basova","sequence":"additional","affiliation":[{"name":"N.I. Vavilov Institute of General Genetics, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Suvorina","sequence":"additional","affiliation":[{"name":"N.I. Vavilov Institute of General Genetics, Moscow 119991, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1757-4683","authenticated-orcid":false,"given":"Mikhail","family":"Donskoy","sequence":"additional","affiliation":[{"name":"JSC \u00abEuropean Medical Center\u00bb, Moscow 129110, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6954-1564","authenticated-orcid":false,"given":"Ivan","family":"Abramov","sequence":"additional","affiliation":[{"name":"SBIH Moscow Clinical Scientific and Practical Center Named after A.S. Loginov of DHM Moscow, Moscow 111123, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Bodunova","sequence":"additional","affiliation":[{"name":"SBIH Moscow Clinical Scientific and Practical Center Named after A.S. Loginov of DHM Moscow, Moscow 111123, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saida","family":"Gadzhieva","sequence":"additional","affiliation":[{"name":"Moscow Healthcare Department, 43 Oruzheynyy Pereulok, Moscow 127006, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Semina","sequence":"additional","affiliation":[{"name":"Moscow Healthcare Department, 43 Oruzheynyy Pereulok, Moscow 127006, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Andreev","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Lysenko","sequence":"additional","affiliation":[{"name":"Moscow Clinical Science and Research Center 52, Moscow 109428, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/j.seminhematol.2023.11.006","article-title":"Biological heterogeneity in diffuse large B-cell lymphoma","volume":"60","author":"Hilton","year":"2023","journal-title":"Semin. 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