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Vascular events and risk factors for thrombosis in refractory anemia with ring sideroblasts and thrombocytosis

Leukemia volume 30, pages 2273–2275 (2016)Cite this article

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Refractory anemia with ring sideroblasts and thrombocytosis (RARS-T) is a provisional entity in the World Health Organization (WHO) classification of myelodysplastic/myeloproliferative overlap syndromes, with diagnostic features of RARS, along with a platelet count >450 × 109/l and large atypical bone marrow (BM) megakaryocytes.1, 2 Patients with RARS-T have a unique mutational landscape, with frequent mutations involving; SF3B1 (~85%), JAK2 (~50%), ASXL1 (~30%), TET2 (~25%), SETBP1 (~15%) and DNMT3A (~15%).3, 4 The frequency of thrombotic events in RARS-T is thought to be similar to that of essential thrombocytosis (ET) (3.6 vs 3.9/100 patient-years), but more frequent than RARS (3.6 vs 0.9/100 patient-years).5 However, unlike in ET, it remains unclear as to whether thrombotic events in RARS-T impact overall survival (OS).6 In a prior study (n=15), 6 of 10 (60%) patients with SF3B1mut RARS-T had thrombotic events; whereas there were no thrombotic events in SF3B1wt patients.7 We carried out this study to (i) describe vascular events, (ii) identify risk factors for thrombosis and (iii) determine the impact of thrombotic events on OS in patients with RARS-T.

Eighty two patients with WHO-defined RARS-T were included in the study.4 All patients had BM aspirates and core biopsies, iron stains for detection of BM ring sideroblasts (RS) and cytogenetics performed at diagnosis. A 27-gene panel-targeted capture assay was carried out on BM DNA specimens from 48 (59%) RARS-T patients obtained at diagnosis for the following genes: TET2, DNMT3A, IDH1, IDH2, ASXL1, EZH2, SUZ12, SRSF2, SF3B1, ZRSR2, U2AF1, PTPN11, Tp53, SH2B3, RUNX1, CBL, NRAS, JAK2, CSF3R, FLT3, KIT, CALR, MPL, NPM1, CEBPA, IKZF and SETBP1, by previously described methods.4 Details of thrombotic events and cardiovascular (CV) risk factors, including hypertension, diabetes, smoking and dyslipidemia, were obtained by careful review of the medical record. OS was calculated from time of initial diagnosis to the time of last follow-up or death. Thrombosis-free survival (TFS) was calculated from the time of diagnosis of RARS-T to development of thrombosis in uncensored patients and date of last follow-up or death in patients censored for thrombosis. Conventional statistics were utilized for all analyses.

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Acknowledgements

This work is supported in part by grants from the ‘The Henry J. Predolin Foundation for Research in Leukemia, Mayo Clinic, Rochester, MN, USA’. This work was supported by CTSA Grant Number KL2 TR000136 from the National Center for Advancing Translational Science (NCATS).

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    M M Patnaik, N Gangat & A Tefferi

  2. Department of Hematology, Mayo Clinic, Rochester, MN, USA

    T L Lasho & C M Finke

  3. Division of Hematopathology, Department of Laboratory Medicine, Mayo Clinic, Rochester, MN, USA

    C A Hanson & R L King

  4. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    R P Ketterling

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  1. M M Patnaik
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  2. T L Lasho
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  3. C M Finke
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  4. C A Hanson
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  5. R L King
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  6. R P Ketterling
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  7. N Gangat
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  8. A Tefferi
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Correspondence to A Tefferi.

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Patnaik, M., Lasho, T., Finke, C. et al. Vascular events and risk factors for thrombosis in refractory anemia with ring sideroblasts and thrombocytosis. Leukemia 30, 2273–2275 (2016). https://doi.org/10.1038/leu.2016.216

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