REAL-WORLD ASSESSMENT OF HYDROXYUREA RESISTANCE AND INTOLERANCE IN POLYCYTHEMIA VERA USING A NATIONWIDE BRAZILIAN ELECTRONIC HEALTH RECORD DATABASE
- 1Novartis Biociências S.A, São Paulo, SP, Brazil
- 2Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil; Grupo Fleury, São Paulo, SP, Brazil
- 3Universidade Federal de Goiás, Goiânia, GO, Brazil
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.
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BibTeX
@article{abuazar2026realworld,
title = {{REAL-WORLD ASSESSMENT OF HYDROXYUREA RESISTANCE AND INTOLERANCE IN POLYCYTHEMIA VERA USING A NATIONWIDE BRAZILIAN ELECTRONIC HEALTH RECORD DATABASE}},
author = {Carolina ABUAZAR and Diogo NOIN DE OLIVEIRA and Ana Beatriz MACHADO DE ALMEIDA and Alessandro BIGONI and Priscilla RAUPP DA ROSA and Michelly Yumi TUBONE DONI and Leonardo Hiago GATTAS and Lucas Kaoru KOBO FERREIRA and Alex FREIRE SANDES and Renato SAMPAIO TAVARES},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107533},
url = {https://doi.org/10.1016/j.htct.2026.107533},
note = {CC BY},
}
RIS
TY - JOUR
TI - REAL-WORLD ASSESSMENT OF HYDROXYUREA RESISTANCE AND INTOLERANCE IN POLYCYTHEMIA VERA USING A NATIONWIDE BRAZILIAN ELECTRONIC HEALTH RECORD DATABASE
AU - Carolina ABUAZAR
AU - Diogo NOIN DE OLIVEIRA
AU - Ana Beatriz MACHADO DE ALMEIDA
AU - Alessandro BIGONI
AU - Priscilla RAUPP DA ROSA
AU - Michelly Yumi TUBONE DONI
AU - Leonardo Hiago GATTAS
AU - Lucas Kaoru KOBO FERREIRA
AU - Alex FREIRE SANDES
AU - Renato SAMPAIO TAVARES
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107533
UR - https://doi.org/10.1016/j.htct.2026.107533
AB - 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.
SN - 2531-1379
SN - 2531-1387
ER -