MYELOPROLIFERATIVE NEOPLASIA ASSOCIATED WITH SPLANCHNIC VEIN THROMBOSIS IS CORRELATED WITH DISTINCT CLINICAL FEATURES AND LOW JAK2 V617F ALLELE BURDEN.
Author(s): ,
Wanda Toscano
Affiliations:
Department of Haematology,University of Birmingham & Queen Elizabeth Hospital NHS Trust,Birmingham B15 2TH,United Kingdom
,
Jane Bryon
Affiliations:
West Midlands Regional Genetics Laboratory,Birmingham Women's Hospital NHS Trust,Birmingham B15 2TG,United Kingdom
,
Tamara Khaguli
Affiliations:
Department of Haematology,University of Birmingham & Queen Elizabeth Hospital NHS Trust,Birmingham B15 2TH,United Kingdom
,
Stephen Jenkins
Affiliations:
Department of Haematology,Russels Hall Hospital,Dudley DY1 2HQ,United Kingdom
,
Mike Griffiths
Affiliations:
West Midlands Regional Genetics Laboratory,Birmingham Women's Hospital NHS Trust,Birmingham B15 2TG,United Kingdom
,
Dhiraj Tripathi
Affiliations:
Department of Hepatology,Queen Elizabeth Hospital NHS Trust,Birmingham B15 2TH,United Kingdom
Frederick Chen
Affiliations:
Department of Haematology,University of Birmingham & Queen Elizabeth Hospital NHS Trust,Birmingham B15 2TH,United Kingdom
EHA Library. Toscano W. 06/11/16; 133561; P673
Ms. Wanda Toscano
Ms. Wanda Toscano
Contributions
Abstract
Abstract: P673

Type: Poster Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 17:30 - 19:00

Location: Poster area (Hall H)

Background
Splanchnic vein thrombosis (SVT) is strongly associated with myeloproliferative neoplasms (MPN) such as Polycythemia Vera (PV), Essential Thrombocythemia (ET), Myelofibrosis (MF). This association was established when routine molecular analysis of JAK2 V6176F mutation was introduced as a diagnostic assessment for MPN. Up to 50 % of Budd-Chiari syndrome and 30% of extraepathic thrombosis are associated with the presence of JAK2 V617F mutation. However, 30% of these patients do not meet the WHO criteria for the diagnosis of PV, ET or MF. 

Aims
The study aims to compare and contrast the pathophysiological and genotypic features of JAK2 V617F positive SVT patients with those meeting the standard diagnostic criteria for MPN. 

Methods
We conducted a retrospective single centre study of 43 patients with JAK2 V617F positive SVT at the Queen Elizabeth Hospital NHS Trust to document the clinical and haematological features of these patients at presentation, their long-term outcome and their JAK2 mutational status and allele burden by quantitative digital droplet PCR. 

Results
SVT occurred before MPN was diagnosed according to WHO criteria in 28 out of 43 patients, and in 3 patients a thrombotic event at a different site occurred before onset of MPN. Within this cohort 18 patients were females and 13 were males. The mean age at diagnosis of SVT/ thrombotic event was 35 years (range 22-67). During follow-up 10 patients developed PV (3 female, 7 males), 7 patients developed ET (3 females, 4 males), 9 patients developed U-MPN (7 females, 2 males), 5 patients did not develop a recognisable MPN at their last follow-up.The median hemoglobin at SVT diagnosis was 14.05 g/dL in females and 14.85 g/dL in males, the median WBC was 9.1x10^9/L, the median platelet count at SVT diagnosis was 266x10^9/L. These values would not have met the WHO diagnostic criteria for ET, PV or MF at diagnosis. In this study we considered JAK2 mutational burden in the range of 0-25% as low, 26-74% as intermediate and >75% as high (AM Vannucchi et al). In our cohort, the median JAK2 mutational burden was in the lower range with a median allele burden of 17% (range 0.6-81%). The median JAK2 mutational burden in the patients diagnosed with SVT without developing MPN at their last follow up had a median allele burden of 14% (range 9.9-22 %), which is lower than the mutational burden found in PV and PMF (26-50%) and similar to ET (0-22%) 

Conclusion
JAK2 V617+ SVT constitute an early but distinct MPN subtype presenting with young age, unremarkable haematolgical parameters and low JAK2 V617F allele burden. 

Session topic: Myeloproliferative neoplasms - Clinical 2 (Poster)
Abstract: P673

Type: Poster Presentation

Presentation during EHA21: On Saturday, June 11, 2016 from 17:30 - 19:00

Location: Poster area (Hall H)

Background
Splanchnic vein thrombosis (SVT) is strongly associated with myeloproliferative neoplasms (MPN) such as Polycythemia Vera (PV), Essential Thrombocythemia (ET), Myelofibrosis (MF). This association was established when routine molecular analysis of JAK2 V6176F mutation was introduced as a diagnostic assessment for MPN. Up to 50 % of Budd-Chiari syndrome and 30% of extraepathic thrombosis are associated with the presence of JAK2 V617F mutation. However, 30% of these patients do not meet the WHO criteria for the diagnosis of PV, ET or MF. 

Aims
The study aims to compare and contrast the pathophysiological and genotypic features of JAK2 V617F positive SVT patients with those meeting the standard diagnostic criteria for MPN. 

Methods
We conducted a retrospective single centre study of 43 patients with JAK2 V617F positive SVT at the Queen Elizabeth Hospital NHS Trust to document the clinical and haematological features of these patients at presentation, their long-term outcome and their JAK2 mutational status and allele burden by quantitative digital droplet PCR. 

Results
SVT occurred before MPN was diagnosed according to WHO criteria in 28 out of 43 patients, and in 3 patients a thrombotic event at a different site occurred before onset of MPN. Within this cohort 18 patients were females and 13 were males. The mean age at diagnosis of SVT/ thrombotic event was 35 years (range 22-67). During follow-up 10 patients developed PV (3 female, 7 males), 7 patients developed ET (3 females, 4 males), 9 patients developed U-MPN (7 females, 2 males), 5 patients did not develop a recognisable MPN at their last follow-up.The median hemoglobin at SVT diagnosis was 14.05 g/dL in females and 14.85 g/dL in males, the median WBC was 9.1x10^9/L, the median platelet count at SVT diagnosis was 266x10^9/L. These values would not have met the WHO diagnostic criteria for ET, PV or MF at diagnosis. In this study we considered JAK2 mutational burden in the range of 0-25% as low, 26-74% as intermediate and >75% as high (AM Vannucchi et al). In our cohort, the median JAK2 mutational burden was in the lower range with a median allele burden of 17% (range 0.6-81%). The median JAK2 mutational burden in the patients diagnosed with SVT without developing MPN at their last follow up had a median allele burden of 14% (range 9.9-22 %), which is lower than the mutational burden found in PV and PMF (26-50%) and similar to ET (0-22%) 

Conclusion
JAK2 V617+ SVT constitute an early but distinct MPN subtype presenting with young age, unremarkable haematolgical parameters and low JAK2 V617F allele burden. 

Session topic: Myeloproliferative neoplasms - Clinical 2 (Poster)

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