Case Presentation: Hydroxyurea Resistance at the Maximum Tolerated Dose in Essential Thrombocythemia
Patient Case:
A 74-year-old woman with coronary artery disease, hypertension, obesity, and JAK2 V617F–positive essential thrombocythemia diagnosed 3 years earlier had no history of thrombosis or hemorrhage. Given her age and JAK2 V617F mutation, she was considered to have high-risk disease and began aspirin 81 mg daily and hydroxyurea (HU) at diagnosis.
Her HU dose ranged from 500 mg to 1000 mg daily, including an intermediate schedule of 500 mg alternating with 1000 mg daily. At 1000 mg daily, her platelet count remained elevated at 490 × 10⁹/L while her hemoglobin decreased to 9.9 g/dL and her WBC count to 2.9 × 10⁹/L. She also developed oral mucositis and increasing fatigue, which limited continued treatment at the higher dose.
After HU was reduced to 500 mg daily, the cytopenias improved, but disease control worsened. At the current evaluation, her platelet count was 799 × 10⁹/L, WBC count was 3.4 × 10⁹/L, and hemoglobin was 10.9 g/dL. She again reported headaches and fatigue. This pattern supported HU resistance at the maximum tolerated dose with overlapping hematologic and nonhematologic intolerance.
Repeat bone marrow biopsy remained consistent with ET, with MF-0 fibrosis and a normal karyotype. Next-generation sequencing identified JAK2 V617F with a variant allele frequency of 36%, with no additional pathogenic mutations reported. Her depression was stable on a low-dose SSRI and was considered when evaluating treatment selection and monitoring. After reviewing the SURPASS-ET evidence and available second-line options, the patient and clinician selected ropeginterferon alfa-2b as the next therapy.
The table below summarizes the patient’s HU dosing, blood count trends, symptoms, and ELN-based clinical assessment at selected time points.
| Time Point | HU Dose | WBC (× 10⁹/L) | Hemoglobin (g/dL) | Platelets (× 10⁹/L) | Symptoms | ELN-based clinical assessment |
| Diagnosis | - | 6.5 | 12.4 | 834 | Headaches and fatigue | - |
| 6 months | 500 mg daily | 4.7 | 11.7 | 645 | Headaches | No response |
| 12 months | 1000 mg daily | 2.9 | 9.9 | 490 | Occasional mouth sores and fatigue | Resistance and intolerance |
| 18 months | 500 mg alternating with 1000 mg daily | 3.5 | 10.3 | 576 | Fatigue and dyspnea | Partial response |
| 24 months | 500 mg daily | 3.4 | 10.9 | 799 | Headaches, fatigue, and dyspnea | No response |
