{
  "abstract": "Background: Venetoclax-based regimens are a known standard of care for acute myeloid leukemia (AML) above 75 years. Recent studies extend this strategy to progressively younger patients, yet whether it benefits those aged 50-75 years, in whom intensive chemotherapy (IC) remains arguable, is unclear, and even less so in low- and middle-income cohorts with higher treatment-related mortality. We characterized the outcomes of this ''gray zone'' of fitness and whether a less intensive treatment could increase early and overall survival of AML patients treated in Brazil. To our knowledge, this is the first national study evaluating this age stratum. Methods: This is a multicenter retrospective cohort study from the Brazilian AML Registry including patients aged 50-75 years with newly diagnosed AML (2021-2025; promyelocytic and biphenotypic leukemias excluded), grouped by treatment received as IC (7+3 +/- targeted agents), venetoclax-based (with hypomethylating agent or low-dose cytarabine), or low-intensity (HMA, cytarabine or hydroxyurea). Genetic risk used the Adapted Genetic Risk (AGR) classification. Outcomes were overall survival (OS), 30-day mortality, non-relapse mortality (NRM), relapse and allogeneic transplantation (allo-HSCT), the last three by competing risks. Because venetoclax is preferentially offered to older, less fit patients, 1:1 propensity score matching (caliper 0.20 SD of the logit; age, Charlson index, healthcare system, AGR) was applied to mitigate confounding by indication. As sensitivity analysis, the Cox model was refitted as a frailty model to account for outcome heterogeneity between public and private centers. Results: Of 374 patients,215 received IC, 116 venetoclax-based, 43 low-intensity therapy; 8.2% of IC-treated patients were considered unfit vs 65.5% in the venetoclax group. Composite complete response was similar (60.2% vs 55.1%; p=0.48), CR predominating after IC (50.0% vs 33.0%) and CRi after venetoclax (21.6% vs 3.4%). At a median follow-up of 21.1 months, median OS was 14.4 months (95% CI 9.5-19.4) with venetoclax vs 3.8 (2.9-5.1) with IC and 2.0 (1.2-7.3) with low-intensity therapy (p<0.001); adjusted HR 0.56 (0.40-0.80), benefit concentrated in the first 6 months (HR 0.38, 0.24-0.61), neutral thereafter (0.98, 0.55-1.76). Thirty-day mortality was 25.1% (IC) vs 5.2% (venetoclax); adjusted OR 6.84 (2.60-20.70). 12-month NRM was 69.6% vs 36.4%, while relapse was higher with venetoclax (20.1% vs 7.6%), consistent with longer survival to relapse; 24-month allo-HSCT incidence was 12.9% for IC vs 37.4% for venetoclax (adjusted sHR 2.61, 1.27-5.36). In 59 matched pairs (all standardized mean differences <0.10), both OS (HR 0.57, 0.36-0.92; p=0.021) and 30-day mortality (25.4% vs 5.1%; p=0.006) still favored venetoclax. In the frailty model the random-effect variance was small and the venetoclax effect unchanged, indicating the advantage is not explained by center heterogeneity. Conclusions: Despite including frailer patients, venetoclax-based therapy outperformed IC at ages 50-75 years, with equivalent response but fivefold lower induction mortality, translating into longer survival and a threefold higher probability of reaching allo-HSCT. The advantage emerged early and persisted after propensity score matching and frailty modelling, suggesting that, in real-world practice, venetoclax-based regimens could overcome the high mortality observed in this Brazilian cohort above 50 years of age, in both public and private settings, by reducing early toxicity.",
  "abstract_shown": true,
  "affiliations": [
    "Instituto D'Or de Pesquisa e Ensino e ICESP-USP, São Paulo, SP, Brazil",
    "Instituto do Câncer do Estado de São Paulo (ICESP-USP), São Paulo, SP, Brazil",
    "Instituto D'or de Pesquisa e Ensino, São Paulo, SP, Brazil",
    "Associação Brasileira de Hematologia, Hemoterapia e Terapia celular, São Paulo, SP, Brazil",
    "Hospital Beneficência Portuguesa, SP, São Paulo, SP, Brazil",
    "AC Camargo Cancer Center, SP, São Paulo, SP, Brazil",
    "Rede D'Or Brasília, Brasília, DF, Brazil",
    "Hemocentro Santa Catarina, Florianópolis, SC, Brazil",
    "Universidade Estadual do Rio de Janeiro (UERJ), Rio de Janeiro, RJ, Brazil",
    "Rede D'Or Pernambuco, Recife, PE, Brazil",
    "Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil",
    "Centro de Oncologia Cascavel, Cascavel, PR, Brazil",
    "Fundação de Saúde Dilson de Quadros Godinho, Montes Claros, MG, Brazil",
    "Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brazil",
    "Hospital das Clínicas da USP-SP e Instituto D'Or de Pesquisa e Ensino, SP, São Paulo, SP, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Luiza Lapolla PERRUSO"
    },
    {
      "affs": [
        1
      ],
      "name": "Wellington Fernandes SILVA"
    },
    {
      "affs": [
        2
      ],
      "name": "Abel COSTA"
    },
    {
      "affs": [
        3
      ],
      "name": "Verena PFISTER"
    },
    {
      "affs": [
        4
      ],
      "name": "Andre Dias AMERICO"
    },
    {
      "affs": [
        5
      ],
      "name": "Marina NASCIMENTO"
    },
    {
      "affs": [
        6
      ],
      "name": "Flavia Dias XAVIER"
    },
    {
      "affs": [
        7
      ],
      "name": "Maria Daniela Houthausen PERICO"
    },
    {
      "affs": [
        8
      ],
      "name": "Renata Lyrio BAPTISTA"
    },
    {
      "affs": [
        9
      ],
      "name": "Reijane ASSIS"
    },
    {
      "affs": [
        10
      ],
      "name": "Yana RABELO"
    },
    {
      "affs": [
        11
      ],
      "name": "Sara RIGO"
    },
    {
      "affs": [
        12
      ],
      "name": "Jose Alfreu Soares JUNIOR"
    },
    {
      "affs": [
        13
      ],
      "name": "Fernanda Rodrigues MENDES"
    },
    {
      "affs": [
        14
      ],
      "name": "Eduardo Magalhães REGO"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/74zdzrbeaqw18.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107574",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926013210",
  "id": "74zdzrbeaqw18",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107574",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC633-647.5"
    ],
    [
      "openalex",
      "2720|Acute Myeloid Leukemia Research"
    ]
  ],
  "openalex": "W7223145778",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/74zdzrbeaqw18.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:37Z",
      "native_id": "d501b5c2278643ae8932cae9fdb2e0da",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.107574"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "lcc:RC633-647.5",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "COMPARISON OF INTENSIVE CHEMOTHERAPY VERSUS VENETOCLAX-BASED REGIMENS IN ADULTS AGED 50-75 YEARS WITH ACUTE MYELOID LEUKEMIA: A PROPENSITY SCORE-MATCHED ANALYSIS",
  "title_text": "COMPARISON OF INTENSIVE CHEMOTHERAPY VERSUS VENETOCLAX-BASED REGIMENS IN ADULTS AGED 50-75 YEARS WITH ACUTE MYELOID LEUKEMIA: A PROPENSITY SCORE-MATCHED ANALYSIS",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:37Z",
  "url": "https://research.draconitic.com/paper/74zdzrbeaqw18",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}