Clinical Features of Patients With Philadelphia-Negative Myeloproliferative Neoplasms Complicated by Portal Hypertension

Yan, Matthew; Geyer, Holly; Mesa, Ruben A.; Atallah, Ehab; Callum, Jeannie; Bartoszko, Justyna; Yee, Karen; Maganti, Manjula; Gupta, Vikas

doi:10.1016/j.clml.2014.04.004

Cited by 25 publications

(24 citation statements)

References 18 publications

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“…A case report described the improvement of esophageal varices secondary to portal hypertension in a patient with MF who had received ruxolitinib . On the opposite, none of three patients with MPN and portal hypertension due to SVT, who were treated with ruxolitinib in another study, showed meaningful change in the grade of esophageal varices …”

Section: Discussionmentioning

confidence: 53%

Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms

et al. 2017

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Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms.

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Section: Discussionmentioning

confidence: 53%

Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms

et al. 2017

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“…The JAK2V617F mutation occurs in 95% of PV and 50–60% of ET and PMF patients, and acquired mutations within CALR and MPL genes account for majority of JAK2 ‐negative ET and PMF . Intriguingly, multiple studies have consistently demonstrated a prominent role of JAK2 V617F in vascular risk generally and MPN‐associated portal hypertension specifically, although the underlying pathobiologic basis is not well understood …”

Section: Introductionmentioning

confidence: 99%

“…Portal hypertension (pHTN) occurs in 7–18% of MPN patients and portends a poor prognosis . The etiologies of pHTN in MPN involve both thrombotic and nonthrombotic mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…The most common cause of MPN‐associated pHTN is splanchnic vein thrombosis (SVT), which includes Budd‐Chiari syndrome (BCS), portal vein thrombosis (PVT), mesenteric vein thrombosis, and splenic vein thrombosis. Extramedullary hematopoiesis (EMH) within the liver and spleen, a common feature of MPN, results in increased sinusoidal resistance and pressure within the portal circulation . Lastly, nodular regenerative hyperplasia (NRH), an under‐recognized entity characterized by regenerative nodules in the absence of fibrosis, has been described in MPN patients with pHTN …”

Section: Introductionmentioning

confidence: 99%

“…MPN‐associated pHTN commonly presents with ascites, gastrointestinal varices, and, rarely, acute liver failure . In contrast to cirrhotic pHTN, hepatic synthetic function is typically preserved in MPN‐associated pHTN; however, this population similarly is at risk for refractory ascites and gastrointestinal bleeding . Standard treatment of MPN‐associated pHTN parallels treatment of cirrhotic pHTN, including diuretics, large‐volume paracentesis, endoscopic variceal surveillance and ligation, and, rarely, orthotopic liver transplant.…”

Section: Introductionmentioning

confidence: 99%

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Multicenter analysis of the use of transjugular intrahepatic portosystemic shunt for management of MPN‐associated portal hypertension

et al. 2017

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BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are clonal stem cell disorders defined by proliferation of one or more myeloid lineages, and carry an increased risk of vascular events and progression to myelofibrosis and leukemia. Portal hypertension (pHTN) occurs in 7–18% of MPN patients via both thrombotic and nonthrombotic mechanisms and portends a poor prognosis. Transjugular intrahepatic portosystemic shunt (TIPS) has been used in the management of MPN-associated pHTN; however, data on long-term outcomes of TIPS in this setting is limited and the optimal management of medically refractory MPN-associated pHTN is not known. In order to assess the efficacy and long-term outcomes of TIPS in MPN-associated pHTN, we performed a retrospective analysis of 29 MPN patients who underwent TIPS at three academic medical centers between 1997 and 2016. The majority of patients experienced complete clinical resolution of pHTN and its clinical sequelae following TIPS. One, two, three, and four-year overall survival post-TIPS was 96.4%, 92.3%, 84.6%, and 71.4%, respectively. However, despite therapeutic anticoagulation, in-stent thrombosis occurred in 31.0% of patients after TIPS, necessitating additional interventions. In conclusion, TIPS can be an effective intervention for MPN-associated pHTN regardless of etiology. However, TIPS thrombosis is a frequent complication in the MPN population and indefinite anticoagulation post-TIPS should be considered.

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Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis

et al. 2022

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Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by inflammation, marrow fibrosis, and an inherent risk of blastic transformation. Hematopoietic allogeneic stem cell transplant is the only potentially curative therapy for this disease, however, survival gains observed for other transplant indications over the past two decades have not been realized for MF. The role of transplantation may also evolve with the use of novel targeted agents. The chronic inflammatory state associated with MF necessitates pretransplantation assessment of end-organ function. Applying the transplant methodology employed for other myeloid disorders to patients with MF fails to acknowledge differences in the underlying disease pathophysiology. Limited understanding of the causes of poor transplant outcomes in this cohort has prevented refinement of transplant eligibility criteria in MF. There is increasing evidence of heterogeneity in molecular disease grade, beyond the clinical manifestations which have traditionally guided transplant timing. Exploring the physiological consequences of disease chronicity unique to MF, acknowledging the heterogeneity in disease grade, and using advanced prognostic models, molecular diagnostics and other organ function diagnostic tools, we present an innovative review of strategies with the potential to improve transplant outcomes in this disease. Larger, prospective studies which consider the impact of molecular-based disease grade are needed for MF transplantation.

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Clinical Features of Patients With Philadelphia-Negative Myeloproliferative Neoplasms Complicated by Portal Hypertension

Cited by 25 publications

References 18 publications

Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms

Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms

Multicenter analysis of the use of transjugular intrahepatic portosystemic shunt for management of MPN‐associated portal hypertension

Innovative strategies to improve hematopoietic stem cell transplant outcomes in myelofibrosis

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