{
  "abstract": "Background: Chimeric antigen receptor T-cell (CAR-T) therapy induces a robust systemic inflammatory response, particularly during cytokine release syndrome (CRS). Although inflammatory toxicities affecting multiple organs have been extensively investigated, little is known about the effects of CAR-T therapy on salivary gland function. This study prospectively evaluated longitudinal changes in salivary flow following anti-CD19 CAR-T-cell therapy. Methods: This prospective longitudinal study included patients aged ≥ 8 years with relapsed or refractory B-cell-mediated diseases and treated with in-house manufactured anti-CD19 CAR-T cells developed by NUTERA (Fundação Hemocentro de Ribeirão Preto – USP). Unstimulated whole saliva was collected according to the Navazesh protocol before lymphodepleting chemotherapy (T0), immediately before CAR-T infusion (T1), and on days +1, +3, +7, +10, +14, +21, +28, +60, and +90. Salivary flow was determined gravimetrically after standardized 5-minute collections performed under fasting morning conditions. For longitudinal analysis, assessments were grouped into four predefined biological phases: pre-lymphodepletion baseline (T0), post-lymphodepletion/pre-infusion (T1), acute inflammatory phase (days +1 to +14), and recovery phase (days +21 to +90), reflecting the biological course of CAR-T-cell therapy. Longitudinal changes were analyzed using linear mixed-effects models. Results: Eleven patients were included (median age, 26-years [IQR 9–45]; 54.5% female), comprising B-cell lymphoma (45.5%), B-cell acute lymphoblastic leukemia (45.5%), and others diseases (9.1%). Patients had received a median of four previous treatment lines (IQR 3–5). CRS occurred in 63.6% of patients and ICANS in 27.3%. Salivary flow declined after lymphodepleting chemotherapy, remained reduced throughout the acute post-infusion period (days +1 to +14), and progressively recovered toward baseline during follow-up. Mixed-effects analysis demonstrated the greatest reduction during the acute inflammatory phase compared with the pre-lymphodepletion baseline (β = -0.478; 95% CI -0.968 to 0.012; p = 0.056). Discussion: The temporal profile observed suggests that salivary gland function may be transiently impaired during the early inflammatory phase of CAR-T-cell therapy. Although statistical significance was narrowly missed, the magnitude, direction, and recovery pattern support a transient functional alteration rather than persistent glandular damage. Importantly, the predefined phase-based analytical strategy reflects the biological course of CAR-T-cell therapy and may contribute to standardizing future longitudinal investigations of oral and salivary outcomes in patients receiving cellular immunotherapies. To our knowledge, this is the first prospective Brazilian longitudinal study evaluating salivary gland function during anti-CD19 CAR-T-cell therapy. Conclusion: Anti-CD19 CAR-T-cell therapy was associated with an early, transient reduction in salivary gland function, supporting further investigation of saliva-based biomarkers and oral complications during cellular immunotherapy.",
  "abstract_shown": true,
  "affiliations": [
    "Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HC-FMRP-USP), Ribeirão Preto, SP, Brazil",
    "Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Juliana Guaraldi SORRENTINO"
    },
    {
      "affs": [
        0
      ],
      "name": "Istefani Silva SOUZA"
    },
    {
      "affs": [
        0
      ],
      "name": "Ana Patricia Espaladori ESKENAZI"
    },
    {
      "affs": [
        0
      ],
      "name": "Mariana Andrade COSTA"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Julia PAGLIARONE"
    },
    {
      "affs": [
        0
      ],
      "name": "Milena Rodrigues VASCONCELOS"
    },
    {
      "affs": [
        1
      ],
      "name": "Evandra Strazza RODRIGUES"
    },
    {
      "affs": [
        0
      ],
      "name": "Camila Derminio DONADEL"
    },
    {
      "affs": [
        0
      ],
      "name": "Diego Villa CLé"
    },
    {
      "affs": [
        0
      ],
      "name": "Rodrigo Tocantins CALADO"
    },
    {
      "affs": [
        0
      ],
      "name": "Leandro Dorigan DE MACEDO"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ebpcng0vvkm54.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.108303",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S253113792602050X",
  "id": "ebpcng0vvkm54",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.108303",
  "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",
      "2730|CAR-T cell therapy research"
    ]
  ],
  "openalex": "W7223096743",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/ebpcng0vvkm54.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:28Z",
      "native_id": "edfb1a20d708483aa861a40acb439e7a",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.htct.2026.108303"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|CAR-T cell therapy research",
      "subfield": "oncology"
    }
  ],
  "title": "PROSPECTIVE LONGITUDINAL EVALUATION OF SALIVARY GLAND FUNCTION DURING ANTI-CD19 CAR-T CELL THERAPY",
  "title_text": "PROSPECTIVE LONGITUDINAL EVALUATION OF SALIVARY GLAND FUNCTION DURING ANTI-CD19 CAR-T CELL THERAPY",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:28Z",
  "url": "https://research.draconitic.com/paper/ebpcng0vvkm54",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}