DOI QR코드

DOI QR Code

Clinical Manifestations and Risk Factors for Complications of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

  • Duangnapasatit, Boonlerd (Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
  • Rattarittamrong, Ekarat (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
  • Rattanathammethee, Thanawat (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
  • Hantrakool, Sasinee (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
  • Chai-Adisaksopha, Chatree (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
  • Tantiworawit, Adisak (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University) ;
  • Norasetthada, Lalita (Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University)
  • Published : 2015.07.13

Abstract

Background: Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by proliferation of one or more myeloid lineages. Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are classical Philadelphia chromosome (Ph)-negative MPN that have a Janus Kinase 2 (JAK2) mutation, especially JAK2V617F in the majority of patients. The major complications of Ph-negative MPNs are thrombosis, hemorrhage, and leukemic transformation. Objective: To study clinical manifestations including symptoms, signs, laboratory findings, and JAK2V617F mutations of Ph-negative MPN (PV, ET and PMF) as well as their complications. Materials and Methods: All Ph-negative MPN (PV, ET and PMF) patients who attended the Hematology Clinic at Maharaj Nakorn Chiang Mai Hospital from January, 1 2003 through December, 31 2013 were retrospectively reviewed for demographic data, clinical characteristics, complete blood count, JAK2V617F mutation analysis, treatment, and complications. Results: One hundred and fifty seven patients were included in the study. They were classified as PV, ET and PMF for 68, 83 and 6 with median ages of 60, 61, and 68 years, respectively. JAK2V617F mutations were detected in 88%, 69%, and 100% of PV, ET and PMF patients. PV had the highest incidence of thrombosis (PV 29%, ET 14%, and PMF 0%) that occurred in both arterial and venous sites whereas PMF had the highest incidence of bleeding (PMF 17%, ET 11%, and PV 7%). During follow up, there was one ET patient that transformed to acute leukemia and five cases that developed thrombosis (three ET and two PV patients). No secondary myelofibrosis and death cases were encountered. Conclusions: Ph-negative MPNs have various clinical manifestations. JAK2V617F mutations are present in the majority of PV, ET, and PMF patients. This study confirmed that thrombosis and bleeding are the most significant complications in patients with Ph-negative MPN.

Keywords

Myeloproliferative neoplasms;polycythemia vera;essential thrombocythemia;primary myelofibrosis

References

  1. Campbell PJ, MacLean C, Beer PA, et al (2012). Correlation of blood counts with vascular complications in essential thrombocythemia: analysis of the prospective PT1 cohort. Blood, 120, 1409-11. https://doi.org/10.1182/blood-2012-04-424911
  2. Carobbio A, Thiele J, Passamonti F, et al (2011). Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: An international study of 891 patients. Blood, 117, 5857-9. https://doi.org/10.1182/blood-2011-02-339002
  3. Cervantes F, Dupriez B, Pereira A, et al (2009). New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood, 113, 2895-901. https://doi.org/10.1182/blood-2008-07-170449
  4. Finazzi1 G, Carobbio A, Thiele J, et al (2012). Incidence and risk factors for bleeding in 1104 patients with essential thrombocythemia or prefibrotic myelofibrosis diagnosed according to the 2008 WHO criteria. Leukemia, 26, 716-9. https://doi.org/10.1038/leu.2011.258
  5. Gangat N, Caramazza D, Vaidya R, et al (2010). DIPSS Plus: A refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol, 29, 392-7.
  6. Klampfl T, Gisslinger H, Harutyunyan AS, et al (2013). Somatic mutations of Calreticulin in myeloproliferative neoplasms. N Engl J Med, 369, 2379-90. https://doi.org/10.1056/NEJMoa1311347
  7. Barbui T, Thiele J, Gisslinger H, et al (2014). Masked polycythemia vera (mPV): results of an international study. Am J Hematol, 89, 52-4. https://doi.org/10.1002/ajh.23585
  8. Budde U, van Gendernen PJ (1997). Acquired von Willebrand disease in patients with high platelet counts. Thromb Hemost, 23, 425-31. https://doi.org/10.1055/s-2007-996119
  9. Kunnim S, Auewarakul J (2010). JAK2 mutation in myeloproliferative neoplasms. J Hematol Transfus Med, 1, 55-62.
  10. Marchioli R, Finazzi G, Landolfi R, et al (2005). Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. J Clin Oncol, 23, 2224-32. https://doi.org/10.1200/JCO.2005.07.062
  11. Passamonti F, Cervantes F, Maria A, et al (2010). A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (InternationalWorking Group for Myeloproliferative Neoplasms Research and Treatment). Blood, 115, 1703-8. https://doi.org/10.1182/blood-2009-09-245837
  12. Passamonti F, Thiele J, Girodon F, et al (2012). A prognostic model to predict survival in 867 World Health Organization.defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment. Blood, 120, 1197-201. https://doi.org/10.1182/blood-2012-01-403279
  13. Barbui T, Barosi G, Birgegard G, et al (2011). Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. J Clin Oncol, 29, 761-70. https://doi.org/10.1200/JCO.2010.31.8436
  14. Barbui T, Finazzi G, Carobbio A, et al (2012). Development and validation of an international prognostic score of thrombosis in world health organization.essential thrombocythemia (IPSET-thrombosis). Blood, 120, 5128-33. https://doi.org/10.1182/blood-2012-07-444067
  15. Sag SM, Gorukmez O, Ture M, et al (2015). MMP2 Gene-735 C/T and MMP9 gene -1562 C/T polymorphisms in JAK2V617F positive myeloproliferative disorders. Asian Pac J Cancer Prev, 16, 443-9. https://doi.org/10.7314/APJCP.2015.16.2.443
  16. Tefferi A, Vardiman JW (2008). Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and proposed diagnosis algorithm. Leukemia, 22, 14-22. https://doi.org/10.1038/sj.leu.2404955
  17. Tefferi A, Rumi E, Finazzi G, et al (2013). Survival and prognosis among 1545 patients with contemporary polycythemia vera: An international study. Leukemia, 27, 1874-81. https://doi.org/10.1038/leu.2013.163
  18. Tefferi A, Guglielmelli P, Larson DR, et al (2014). Long-term survival and blast transformation in molecularly annotated essential thrombocythemia, polycythemia vera, and myelofibrosis. Blood, 124, 2507-13. https://doi.org/10.1182/blood-2014-05-579136
  19. Tefferi A, Thiele J, Vannucchi AM, et al (2014). An overview on CALR and CSF3R mutations and a proposal for revision of WHO diagnostic criteria for myeloproliferative neoplasms. Leukemia, 28, 1407-13. https://doi.org/10.1038/leu.2014.35

Cited by

  1. Acquired JAK-2 V617F Mutational Analysis in Pakistani Patients with Essential Thrombocythemia vol.16, pp.16, 2015, https://doi.org/10.7314/APJCP.2015.16.16.7327
  2. Clinico-Hematological Profile and Risk Stratification in Patients with Essential Thrombocythemia: Experience from Pakistan vol.16, pp.17, 2015, https://doi.org/10.7314/APJCP.2015.16.17.7659
  3. JAK-2 V617F Mutational Analysis in Primary Idiopathic Myelofibrosis: Experience from Southern Pakistan vol.16, pp.17, 2015, https://doi.org/10.7314/APJCP.2015.16.17.7889
  4. Primary Idiopathic Myelofibrosis: Clinico-Epidemiological Profile and Risk Stratification in Pakistani Patients vol.16, pp.18, 2016, https://doi.org/10.7314/APJCP.2015.16.18.8629
  5. Somatic JAK-2 V617F Mutational Analysis in Polycythemia Rubra Vera: a Tertiary Care Center Experience vol.17, pp.3, 2016, https://doi.org/10.7314/APJCP.2016.17.3.1053
  6. Clinico-Epidemiological Profile of Patients with Polycythaemia Rubra Vera - a Five Year Experience from a Tertiary Care Center vol.17, pp.3, 2016, https://doi.org/10.7314/APJCP.2016.17.3.1531
  7. A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms vol.19, pp.1, 2019, https://doi.org/10.1186/s12885-019-5387-9