{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T10:44:05Z","timestamp":1789469045934,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100023181","name":"Medical Research Agency","doi-asserted-by":"crossref","award":["2020\/ABM\/01\/00102"],"award-info":[{"award-number":["2020\/ABM\/01\/00102"]}],"id":[{"id":"10.13039\/501100023181","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2020\/ABM\/01\/00102"],"award-info":[{"award-number":["2020\/ABM\/01\/00102"]}],"id":[{"id":"https:\/\/ror.org\/026nedj88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>Primary and isolated secondary central nervous system lymphomas are aggressive malignancies requiring effective central nervous system\u2013directed therapy. Intensive high-dose methotrexate\u2013based regimens may be difficult to deliver, particularly in older or functionally impaired patients. Berubicin is a doxorubicin analog developed to cross the blood\u2013brain barrier. We report a prospective case series of five adults with primary or isolated secondary CNS lymphoma treated within the BER-PUM phase Ib\/II study (EudraCT 2021-006028-41), evaluating berubicin as part of the investigational MBTRIX regimen. Patients received up to four 21-day cycles of rituximab, high-dose methotrexate, berubicin, and thiotepa, with between-patient and intrapatient berubicin dose escalation. Four out of five patients completed all planned cycles, even though most of the patients had an ECOG score of 2. After two cycles, four achieved partial response, and one had progressive disease. Two patients underwent autologous stem-cell transplantation; one achieved complete response maintained at 12 months, whereas the other died from severe infectious and multiorgan complications. All patients experienced at least one grade \u2265 3 adverse event, predominantly hematologic. No protocol-defined dose-limiting toxicity or berubicin dose reduction occurred. Recruitment ended prematurely because berubicin became unavailable. This case series demonstrates the feasibility of MBTRIX, although the small sample and incomplete dose escalation preclude definitive conclusions regarding safety and efficacy.<\/jats:p>","DOI":"10.3390\/curroncol33090557","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T08:16:48Z","timestamp":1789460208000},"page":"557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Berubicin Substituted for Cytarabine in a MATRix-Based Regimen for Isolated Central Nervous System Lymphoma: A Five-Patient Case Series from the BER-PUM Study"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4445-6192","authenticated-orcid":false,"given":"S\u0142awomir","family":"Milczarek","sequence":"first","affiliation":[{"name":"Department of Hematology and Transplantology, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliwia","family":"Piotrowska","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transplantology, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-5844","authenticated-orcid":false,"given":"Bart\u0142omiej","family":"Baumert","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transplantology, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Borowiecka","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transplantology, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Sommerfeld","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transplantology, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Hnatyszyn","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transplantology, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogus\u0142aw","family":"Machali\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Hematology and Transplantology, Pomeranian Medical University, 71-252 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1182\/blood.2020008377","article-title":"Primary central nervous system lymphoma","volume":"140","author":"Schaff","year":"2022","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jiang, H., and Nong, L. (2025). The landscape of primary central nervous system lymphoma: Clinicopathologic and genomic characteristics and therapeutic perspectives. Cancers, 17.","DOI":"10.3390\/cancers17172909"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.1002\/hem3.89","article-title":"Primary central nervous system lymphomas: EHA\u2013ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"8","author":"Ferreri","year":"2024","journal-title":"HemaSphere"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e217","DOI":"10.1016\/S2352-3026(16)00036-3","article-title":"Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: Results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial","volume":"3","author":"Ferreri","year":"2016","journal-title":"Lancet Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1038\/s41375-022-01582-5","article-title":"Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial","volume":"36","author":"Ferreri","year":"2022","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1200\/JCO.18.00306","article-title":"Radiotherapy or autologous stem-cell transplantation for primary CNS lymphoma in patients 60 years of age and younger: Results of the Intergroup ANOCEF-GOELAMS randomized phase II PRECIS study","volume":"37","author":"Houillier","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1182\/blood-2014-10-604561","article-title":"R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma","volume":"125","author":"Omuro","year":"2015","journal-title":"Blood"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3061","DOI":"10.1200\/JCO.2012.46.9957","article-title":"Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202)","volume":"31","author":"Rubenstein","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1200\/JCO.2013.50.4910","article-title":"Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: Final results and long-term outcome","volume":"31","author":"Morris","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10637-006-9018-3","article-title":"The 4\u2032-O-benzylated doxorubicin analog WP744 overcomes resistance mediated by P-glycoprotein, multidrug resistance protein and breast cancer resistance protein in cell lines and acute myeloid leukemia cells","volume":"25","author":"Brooks","year":"2007","journal-title":"Investig. 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Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1200\/JCO.1996.14.2.556","article-title":"Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: Initial report of Radiation Therapy Oncology Group protocol 88-06","volume":"14","author":"Schultz","year":"1996","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/j.ijrobp.2010.06.002","article-title":"CHOD\/BVAM chemotherapy and whole-brain radiotherapy for newly diagnosed primary central nervous system lymphoma","volume":"81","author":"Laack","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_15","first-page":"B101","article-title":"Phase I clinical pharmacokinetics of RTA 744 (berubicin), a blood\u2013brain barrier-penetrating anthracycline active against high-grade glioma, and evaluation of its 13-hydroxy metabolite, berubicinol","volume":"6","author":"Kazerooni","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1200\/jco.2007.25.18_suppl.2062","article-title":"Final results of a phase I trial with the novel anthracycline derivative RTA 744 in patients with primary brain tumors","volume":"25","author":"Conrad","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"v144","DOI":"10.1093\/neuonc\/noaf201.0569","article-title":"CTNI-74. Primary results of the randomized clinical trial of berubicin vs. lomustine in patients with glioblastoma after failure of primary therapy: Data analysis and future possibilities","volume":"27","author":"Kashraw","year":"2025","journal-title":"Neuro-Oncology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5034","DOI":"10.1200\/JCO.2005.13.524","article-title":"Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma","volume":"23","author":"Abrey","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/neuonc\/noac196","article-title":"European Association of Neuro-Oncology (EANO) guidelines for treatment of primary central nervous system lymphoma (PCNSL)","volume":"25","author":"Deckert","year":"2023","journal-title":"Neuro-Oncology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1111\/bjh.16451","article-title":"Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system: An international study of feasibility and efficacy in routine clinical practice","volume":"189","author":"Schorb","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e70142","DOI":"10.1002\/hon.70142","article-title":"Long-term real-world outcomes of primary CNS lymphoma patients treated with MATRix regimen are similar to IELSG32 trial results","volume":"43","author":"Vodicka","year":"2025","journal-title":"Hematol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e110","DOI":"10.1016\/S2352-3026(20)30366-5","article-title":"MATRix\u2013RICE therapy and autologous haematopoietic stem-cell transplantation in diffuse large B-cell lymphoma with secondary CNS involvement (MARIETTA): An international, single-arm, phase 2 trial","volume":"8","author":"Ferreri","year":"2021","journal-title":"Lancet Haematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3324\/haematol.2021.278613","article-title":"Diffuse large B-cell lymphoma involving the central nervous system: Biologic rationale for targeted therapy","volume":"109","author":"Roschewski","year":"2024","journal-title":"Haematologica"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1182\/blood.2025031455","article-title":"Treatment-related outcomes and patterns of relapse in secondary CNS involvement by large B-cell lymphoma","volume":"147","author":"Alderuccio","year":"2026","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e35770","DOI":"10.1097\/MD.0000000000035770","article-title":"Anthracyclines and the risk of arrhythmias: A systematic review and meta-analysis","volume":"102","author":"Dean","year":"2023","journal-title":"Medicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1002\/rth2.12415","article-title":"Venous thromboembolism in primary central nervous system lymphoma during frontline chemoimmunotherapy","volume":"4","author":"Yuen","year":"2020","journal-title":"Res. Pract. Thromb. Haemost."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e196","DOI":"10.1016\/S2352-3026(23)00371-X","article-title":"High-dose chemotherapy and autologous haematopoietic stem-cell transplantation in older, fit patients with primary diffuse large B-cell CNS lymphoma (MARTA): A single-arm, phase 2 trial","volume":"11","author":"Schorb","year":"2024","journal-title":"Lancet Haematol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/S0140-6736(26)00917-7","article-title":"High-dose chemotherapy followed by autologous stem-cell transplantation versus non-myeloablative consolidation in primary CNS lymphoma (MATRix\/IELSG43): A randomised phase 3 trial","volume":"408","author":"Illerhaus","year":"2026","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e510","DOI":"10.1016\/S2352-3026(17)30174-6","article-title":"Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: Results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial","volume":"4","author":"Ferreri","year":"2017","journal-title":"Lancet Haematol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e388","DOI":"10.1016\/S2352-3026(16)30050-3","article-title":"High-dose chemotherapy with autologous haemopoietic stem-cell transplantation for newly diagnosed primary CNS lymphoma: A prospective, single-arm, phase 2 trial","volume":"3","author":"Illerhaus","year":"2016","journal-title":"Lancet Haematol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"116789","DOI":"10.1016\/j.ejca.2026.116789","article-title":"The long-term efficacy and safety of high-dose chemotherapy with autologous stem cell transplantation in the treatment of primary central nervous system lymphoma: A real-world report from the Polish Lymphoma Research Group","volume":"241","author":"Ostrowska","year":"2026","journal-title":"Eur. J. Cancer"}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/9\/557\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:28:56Z","timestamp":1789464536000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/33\/9\/557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":31,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["curroncol33090557"],"URL":"https:\/\/doi.org\/10.3390\/curroncol33090557","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}