SYTHROM Cohort, Myeloproliferative Neoplasia With Normal CBC and Thrombotic Complications

NCT04539678 | Completed

• 1 other identifier: RC20_0141
• Study Type: observational
• Target: 253
• Locations: 1 country
• Sites: 1

Brief Summary

Among the etiologies of thrombosis, myeloproliferative neoplasia (MPN) is quite rare but should be investigated in case of thrombosis of atypical localization (digestive or cerebral) or in the context of recurrent idiopathic thrombosis in a young subject. Thrombosis could reveal an underlying MPN through the identification of a JAK2 V617F mutation. Rarely, MPN with thrombotic complications present with normal complete blood count(CBC). In case of a MPN with a thrombotic event but without CBC abnormality, anti-thrombotic treatment is recommended. But there is no recommendation for the indication of cytoreductive therapy and the clinician's decision is often empirical. One of the major complications of for essential thrombocythemia (ET) or polycythemia vera (PV) is thrombosis and an age over 60 is a major risk factor. The treatment of thrombosis associated with TE or PV is based on recommendations the main therapeutic objective of which is to reduce the thrombotic risk. The combination of a cytoreducing agent and antithrombotic treatment is thus proposed in high-risk patients. The efficacy of this management is monitored by assessing CBC with the objective of normalization at \<400 G/L of platelets for ET patients and \<45% hematocrit in case of PV. The absence of abnormal CBC makes it difficult to justify cytoreduction. The benefit of such a therapy in this context has not been clinically demonstrated. If a cytoreductive therapy is initiated, no biological parameters are available to assess the response to treatment. The objective of this observational study is to evaluate the incidence of recurrence of thrombosis in patients whose thrombotic event revealed an underlying MPN with normal CBC. A comparison of groups treated or not with cytoreductive agents will be performed. Longitudinal monitoring of the patients will provide a better understanding of the nature and kinetics of hematological changes in these patients.

Conditions

Thrombotic Patients; Diagnosis of Myeloproliferative Neoplasia; Impact of Treatment With Cytoreducing Agent

Keywords

Thrombosis; Myeloproliferative neoplasm; Hydroxyurea; Interferon

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of recurrence of thromboembolic events after the initial thrombosis leading to the diagnosis of MPN

  The diagnosis of thromboembolic events must be confirmed by imaging

  24 months follow-up

Secondary Outcomes (2)

• Cumulative incidence of hematological progression to essential thrombocythemia, polycythemia vera, secondary myelofibrosis or acute transformation

  24 months follow-up

• Cumulative incidence of recurrence of thromboembolic events according to the type and duration of anticoagulant or anti-aggregant treatment

  24 months follow-up

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Thrombosis recurrence :treated and untreated patients with cytoreductive agents

You may qualify if:

• Adult ≥18 years old
• Diagnosis of a deep arterial or venous thrombotic event verified by imaging (Doppler or CT scan)
• Diagnosis of MPN with normal CBC according to WHO 2017 criteria characterized by the detection of a molecular abnormality JAK2V617F mutation (regardless of allelic load), CALR or MPL and/or a bone marrow biopsy with abnormalities in favor of MPN.
• Normal blood cell count not suggestive of polycythemia vera (hematocrit\<48% and hemoglobin\<16g/dL for women; hematocrit\<49% and hemoglobin\<16.5g/dL for men), essential thrombocythemia (platelets\<450 G/L) nor myelofibrosis (white blood cell count\<11 G/L, no anemia or erythromyelemia associated with splenomegaly) at the time of the thrombotic event.

You may not qualify if:

• Minors (\<18 years of age)
• Microcirculation disorders (erythromelalgia, headaches, paresthesia, ischemia of the extremities)
• Superficial or deep arterial or venous thrombosis NOT verified by imaging
• Diagnosis or history of TE, PV or myelofibrosis at time of first thrombotic event
• Diagnosis of mixed myelodysplastic/myeloproliferative syndrome
• Diagnosis of unclassifiable MPN with excess blasts at the onset or signs of myelodysplasia as defined by the WHO 2017 classification

Sponsors & Collaborators

• Nantes University Hospital: lead
• French Intergroup of Myeloproliferative syndromes: collaborator

Study Sites (1)

Nantes University Hospital

Nantes, Loire-Atlantique, 44093, France

Location

Related Publications (7)

• Kiladjian JJ, Cervantes F, Leebeek FW, Marzac C, Cassinat B, Chevret S, Cazals-Hatem D, Plessier A, Garcia-Pagan JC, Darwish Murad S, Raffa S, Janssen HL, Gardin C, Cereja S, Tonetti C, Giraudier S, Condat B, Casadevall N, Fenaux P, Valla DC. The impact of JAK2 and MPL mutations on diagnosis and prognosis of splanchnic vein thrombosis: a report on 241 cases. Blood. 2008 May 15;111(10):4922-9. doi: 10.1182/blood-2007-11-125328. Epub 2008 Feb 4.

  PMID: 18250227 BACKGROUND

• De Stefano V, Fiorini A, Rossi E, Za T, Farina G, Chiusolo P, Sica S, Leone G. Incidence of the JAK2 V617F mutation among patients with splanchnic or cerebral venous thrombosis and without overt chronic myeloproliferative disorders. J Thromb Haemost. 2007 Apr;5(4):708-14. doi: 10.1111/j.1538-7836.2007.02424.x. Epub 2007 Jan 29.

  PMID: 17263783 BACKGROUND

• Levraut M, Legros L, Drappier C, Bene MC, Queyrel V, Raynaud S, Martis N. Low prevalence of JAK2 V617F mutation in patients with thrombosis and normal blood counts: a retrospective impact study. J Thromb Thrombolysis. 2020 Nov;50(4):995-1003. doi: 10.1007/s11239-020-02100-z.

  PMID: 32266587 BACKGROUND

• Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, Rodeghiero F, d'Amore ES, Randi ML, Bertozzi I, Marino F, Vannucchi AM, Antonioli E, Carrai V, Gisslinger H, Buxhofer-Ausch V, Mullauer L, Carobbio A, Gianatti A, Gangat N, Hanson CA, Tefferi A. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011 Aug 10;29(23):3179-84. doi: 10.1200/JCO.2010.34.5298. Epub 2011 Jul 11.

  PMID: 21747083 BACKGROUND

• Barbui T, Finazzi G, Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F, Randi ML, Bertozzi I, Gisslinger H, Buxhofer-Ausch V, De Stefano V, Betti S, Rambaldi A, Vannucchi AM, Tefferi A. Development and validation of an International Prognostic Score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis). Blood. 2012 Dec 20;120(26):5128-33; quiz 5252. doi: 10.1182/blood-2012-07-444067. Epub 2012 Oct 1.

  PMID: 23033268 BACKGROUND

• Pearson TC, Wetherley-Mein G. Vascular occlusive episodes and venous haematocrit in primary proliferative polycythaemia. Lancet. 1978 Dec 9;2(8102):1219-22. doi: 10.1016/s0140-6736(78)92098-6.

  PMID: 82733 BACKGROUND

• Barosi G, Birgegard G, Finazzi G, Griesshammer M, Harrison C, Hasselbalch HC, Kiladjian JJ, Lengfelder E, McMullin MF, Passamonti F, Reilly JT, Vannucchi AM, Barbui T. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood. 2009 May 14;113(20):4829-33. doi: 10.1182/blood-2008-09-176818. Epub 2009 Mar 10.

  PMID: 19278953 BACKGROUND

MeSH Terms

Conditions

Thrombosis; Myeloproliferative Disorders

Condition Hierarchy (Ancestors)

Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Yannick LE BRIS, PhD

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2020
• First Posted: September 7, 2020
• Study Start: May 21, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: February 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)