{
  "abstract": "Background: Hydroxyurea (HU) is the standard first-line cytoreductive therapy for patients with polycythemia vera (PV). However, resistance and intolerance remain important unmet clinical needs and compromise adequate hematologic control and long-term disease management. Aim: This study aimed to estimate the proportion of patients with PV who met established laboratory-based proxy criteria for HU resistance or intolerance. Material and methods: This retrospective study used TriNetX Dataworks Network data from 2014-2026, including Brazilian patients with PV identified by ICD-10 code D45. Patients receiving HU after PV diagnosis were classified according to laboratory-based proxy definitions adapted from established European LeukemiaNet criteria. HU resistance was defined as persistent inadequate hematologic control after ≥3 months of HU treatment, including hematocrit (HCT) ≥45%, HCT <45% with evidence of ongoing phlebotomy requirements, leukocyte count >10,000 cells/mm³, or platelet count >400,000 cells/mm³. HU intolerance was defined by treatment-associated cytopenias, including neutrophil count <1,000 cells/mm³, platelet count <100,000 cells/mm³, or hemoglobin <10 g/dL. Results: Among 2,504 patients with PV, 683 (27.3%) received HU and were eligible for the assessment of laboratory-based proxies suggestive of HU resistance and intolerance. Overall, 167 (24.5%) met at least one laboratory-based proxy criterion for HU resistance. Persistent HCT ≥45%, was the most frequent resistance criterion, observed in 152 of 343 evaluable patients (44.3%). An additional 10 patients met the resistance proxy criterion through HCT <45% with a history of phlebotomy. Elevated leukocyte counts (>10,000 cells/mm³) were observed in 10 of 302 (3.3%) patients with available data, whereas no patients met the platelet criterion (>400,000 cells/mm³) among the 371 patients with available platelet measurements. Additionally, 332 patients (48.6%) met at least one laboratory-based proxy criterion suggestive of HU intolerance. Among patients with available laboratory data approximately 1 month after HU initiation, thrombocytopenia (platelet count <100,000 cells/mm³) was observed in 329 of 344 (95.6%) patients, neutropenia (neutrophil count <1,000 cells/mm³) in 91 of 92 (98.9%) patients, and anemia (hemoglobin <10 g/dL) in 90 of 343 (26.2%) patients. Because patients could meet more than one criterion, the overall prevalence of intolerance reflects unique patients rather than the sum of individual laboratory abnormalities. Conclusions: In this real-world analysis of Brazilian patients with PV, approximately one-quarter of HU-treated patients met laboratory-based proxy criteria suggestive of suboptimal hematologic response, primarily driven by persistent HCT elevation despite treatment. In addition, a substantial proportion of patients developed cytopenias suggestive of HU intolerance. This high frequency should be interpreted with caution, as patients with available laboratory data may represent a selected subgroup with greater disease severity, which may lead to a potential selection bias. Due to the lack of HU dosing data, dose modifications and clinical information, these findings should be interpreted as surrogate markers rather than confirmed HU resistance or intolerance. These findings highlight suboptimal outcomes with HU and may help identify individuals who could benefit from closer monitoring or alternative therapeutic strategies.",
  "abstract_shown": true,
  "affiliations": [
    "Novartis Biociências S.A, São Paulo, SP, Brazil",
    "Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil; Grupo Fleury, São Paulo, SP, Brazil",
    "Universidade Federal de Goiás, Goiânia, GO, Brazil"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Carolina ABUAZAR"
    },
    {
      "affs": [
        0
      ],
      "name": "Diogo NOIN DE OLIVEIRA"
    },
    {
      "affs": [
        0
      ],
      "name": "Ana Beatriz MACHADO DE ALMEIDA"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessandro BIGONI"
    },
    {
      "affs": [
        0
      ],
      "name": "Priscilla RAUPP DA ROSA"
    },
    {
      "affs": [
        0
      ],
      "name": "Michelly Yumi TUBONE DONI"
    },
    {
      "affs": [
        0
      ],
      "name": "Leonardo Hiago GATTAS"
    },
    {
      "affs": [
        0
      ],
      "name": "Lucas Kaoru KOBO FERREIRA"
    },
    {
      "affs": [
        1
      ],
      "name": "Alex FREIRE SANDES"
    },
    {
      "affs": [
        2
      ],
      "name": "Renato SAMPAIO TAVARES"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0h3xsppp274fy.bib",
  "cited_by": 0,
  "doi": "10.1016/j.htct.2026.107533",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926012800",
  "id": "0h3xsppp274fy",
  "issns": [
    "2531-1379",
    "2531-1387"
  ],
  "landing_url": "https://doi.org/10.1016/j.htct.2026.107533",
  "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",
      "2716|Myeloproliferative Neoplasms: Diagnosis and Treatment"
    ]
  ],
  "openalex": "W7223570386",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/0h3xsppp274fy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:25Z",
      "native_id": "2ab41b10bfac4d1a8258328dab1242bc",
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      "url": "https://doi.org/10.1016/j.htct.2026.107533"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Myeloproliferative Neoplasms: Diagnosis and Treatment",
      "subfield": "human-genetics"
    }
  ],
  "title": "REAL-WORLD ASSESSMENT OF HYDROXYUREA RESISTANCE AND INTOLERANCE IN POLYCYTHEMIA VERA USING A NATIONWIDE BRAZILIAN ELECTRONIC HEALTH RECORD DATABASE",
  "title_text": "REAL-WORLD ASSESSMENT OF HYDROXYUREA RESISTANCE AND INTOLERANCE IN POLYCYTHEMIA VERA USING A NATIONWIDE BRAZILIAN ELECTRONIC HEALTH RECORD DATABASE",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:25Z",
  "url": "https://research.draconitic.com/paper/0h3xsppp274fy",
  "venue": "Hematology, Transfusion and Cell Therapy",
  "versions": []
}