Abstract
Hydroxyurea (HU) constitutes the first-line treatment in most patients with essential thrombocythemia (ET), but criteria for changing therapy are not clearly established. The prognostic value of complete hematological response (CHR) and resistance/intolerance to HU was assessed in 1080 patients from the Spanish Registry of ET, classified according to revised IPSET-Thrombosis stratification (Very low- n = 61, Low- n = 83, Intermediate- n = 261, and High-risk n = 675). With a median therapy duration of 5 years, CHR was registered in 720 (67%) patients (1-year probability 51%) and resistance/intolerance in 219 (20%) patients (5-years probability 13%). After correction by other risk factors, High-risk patients achieving CHR showed a reduced risk of arterial thrombosis (HR: 0.35, 95%CI: 0.2–0.6, p = 0.001) and a trend towards lower risk of venous thrombosis (HR: 0.45, 95%CI: 0.2–1.02, p = 0.06) whereas no association was observed for intermediate- or low-risk patients. In comparison with non-responders, intermediate- and high-risk patients achieving CHR had longer survival and lower myelofibrosis incidence. Development of resistance/intolerance to HU, mainly cytopenia, was associated with higher probability of myelofibrosis but no effect on survival or thrombotic risk was demonstrated. In conclusion, CHR with HU is associated with better outcomes and might be an early indicator for selecting candidates to second-line clinical trials.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We are indebted to all members of GEMFIN participating in the Spanish Registry of Essential thrombocythemia. We thank MFAR staff for their technical assistance.
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AAL designed the study, collected the data, performed the statistical analysis, analyzed and interpreted the results and wrote the paper. MS, MG, EAR and JCHB: collected the data, analyzed and interpreted the results, and wrote the paper. MSN, MPE, AS, RPL, FFM, GCT, GC, EM, PV, MACV, AM, AA, IPG, JMG, CGH, MIM, RS, MTGC, LF, BC, VGG, and AT collected the data, interpreted the results and approved the final version.
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The Spanish registry of Essential thrombocythemia is financed with GEMFIN’s own funds without direct collaboration from any pharmaceutical company. This work has been funded by Instituto de Salud Carlos III (ISCIII) through the projects PI21/00231, PI21/00347, and PI21/00538 and co-funded by the European Union.
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Santaliestra, M., Garrote, M., Noya, M.S. et al. Prognostic value of response to first-line hydroxyurea according to IPSET stratification in essential thrombocythemia. Leukemia 38, 2636–2643 (2024). https://doi.org/10.1038/s41375-024-02416-2
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DOI: https://doi.org/10.1038/s41375-024-02416-2
