Impact of comorbidities and body mass index on the outcome of polycythemia vera patients

Benevolo, Giulia; Elli, Elena Maria; Bartoletti, Daniela; Latagliata, Roberto; Tiribelli, Mario; Heidel, Florian H.; Cavazzini, Francesco; Bonifacio, Massimiliano; Crugnola, Monica; Binotto, Gianni; D'Addio, Alessandra; Tieghi, Alessia; Bergamaschi, Micaela; Caocci, Giovanni; Polverelli, Nicola; Bossi, Elisa; Auteri, Giuseppe; Carmosino, Ida; Catani, Lucia; Cuneo, Antonio; Krampera, Mauro; Lanza, Francesco; Lemoli, Roberto M.; Vianelli, Nicola; Breccia, Massimo; Palumbo, Giuseppe; Cavo, Michèle; Palandri, Francesca

doi:10.1002/hon.2843

Cited by 12 publications

(11 citation statements)

References 37 publications

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“…Conventional stroke risk factors, such as hypertension and carotid atherosclerosis, were similarly distributed among patients with and without CBIs. The prevalence of arterial hypertension was ≈20% in both groups, which is lower than in several previous studies (64% in patients with PV and ET in [ 16 ]; 52.3% in PV patients in a study by Bevevolo et al [ 17 ]), which in part may be attributed to a younger age. The latter study [ 17 ] also found hypertension to be associated with increased thrombotic risk (hazard ratio (HR)—1.77 (95% CI: 1.03–3.06; p = 0.04).…”

Section: Discussioncontrasting

confidence: 67%

“…The prevalence of arterial hypertension was ≈20% in both groups, which is lower than in several previous studies (64% in patients with PV and ET in [ 16 ]; 52.3% in PV patients in a study by Bevevolo et al [ 17 ]), which in part may be attributed to a younger age. The latter study [ 17 ] also found hypertension to be associated with increased thrombotic risk (hazard ratio (HR)—1.77 (95% CI: 1.03–3.06; p = 0.04). Carotid atherosclerosis was non-significantly more prevalent in patients with CBIs, and according to limited data on ET patients [ 18 ], no significant differences were found in carotid artery atherosclerosis vs. the control group.…”

Section: Discussioncontrasting

confidence: 67%

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Covert Brain Infarcts in Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders

Кузнецова

Raskurazhev

Konovalov

et al. 2021

JCM

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Backgrounds and Purpose. Philadelphia chromosome-negative myeloproliferative disorders (Ph-negative MPD) are a rare group of hematological diseases, including three distinct pathologies: essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). They most often manifest with thrombotic complications, including cerebrovascular events. Covert brain infarcts (CBIs) are defin ed as predominantly small ischemic cerebral lesions that are detected using magnetic resonance imaging (MRI) in the absence of clinical stroke events. The relationship between MPD and CBIs remains unclear. Methods. Included in the study were 103 patients with the diagnosis of Ph-MPD (according to WHO 2016 criteria) (median age—47 (35; 54) years; 67% female). In total, 38 patients had ET, 42 had PV, and 23 had PMF. They underwent clinical examination, routine laboratory analyses (complete blood count), brain MRI, ultrasound carotid artery, flow-mediated dilatation (as a measure of endothelial dysfunction—FMD). Results. Overall, 23 patients experienced an ischemic stroke (as per MRI and/or clinical history), of which 16 (15.5%) could be classified as CBIs. The rate of CBIs per MPD subtype was statistically non-significant between groups (p = 0.35): ET–13.2%, PV–21.4%, and PMF–8.7%. The major vascular risk factors, including arterial hypertension, carotid atherosclerosis, and prior venous thrombosis, were not associated with CBIs (p > 0.05). Age was significantly higher in patients with CBIs compared to patients without MRI ischemic lesions: 50 (43; 57) years vs. 36 (29; 48) (p = 0.002). The frequency of headaches was comparable between the two groups. CBIs were associated with endothelial dysfunction (OR - 0.71 (95% CI: 0.49–0.90; p = 0.02)) and higher hemoglobin levels (OR—1.21 (95% CI: 1.06–1.55); p =0.03). Conclusions. CBIs are common in patients with Ph-negative MPD. Arterial hypertension and carotid atherosclerosis were not associated with CBIs in this group of patients. The most significant factors in the development of CBIs were endothelial dysfunction (as measured by FMD) and high hemoglobin levels. Patients with Ph-negative MPD and CBIs were older and had more prevalent endothelial dysfunction.

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Section: Discussioncontrasting

confidence: 67%

Section: Discussioncontrasting

confidence: 67%

Covert Brain Infarcts in Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders

Кузнецова

Raskurazhev

Konovalov

et al. 2021

JCM

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“…While age was the main factor accounting for high-risk status followed by thromboembolic complications, the vast majority of patients (> 85%) could be categorized as high risk. Unexpectedly and in contrast to published datasets (Benevolo et al 2021 ) the indication and use of pharmacologic cytoreduction was highly variable in this chart review. While at least 85% of patients had a clear indication for pharmacologic cytoreduction at the time of analysis, only 60.7% received cytoreductive medication, with a high inter-center variability (10.1–100%).…”

Section: Discussioncontrasting

confidence: 56%

“…1 A, B). This aspect is of major importance as recent studies have highlighted the impact of comorbidities on the outcome of polycythemia vera patients (Benevolo et al 2021 ). Taken together, this data indicates a patient population with a high-risk profile (more than 90% of individuals) regarding thromboembolic complications according to conventional risk stratifications.…”

Section: Resultsmentioning

confidence: 99%

Cytoreductive treatment in real life: a chart review analysis on 1440 patients with polycythemia vera

Crodel

Jentsch-Ullrich

Reiser³

et al. 2021

J Cancer Res Clin Oncol

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Purpose Patients with polycythemia vera (PV) show an elevated incidence of thromboembolic complications and decreased survival when compared to age-matched healthy individuals. Hypercellularity as indicated by elevated hematocrit, pathophysiological changes induced by the JAK2 driver mutation and cardiovascular risk factors contribute to the increased incidence of thromboembolic events. Higher age and a history of thromboembolic events define a high-risk population of PV patients. Depending on the individual risk profile, phlebotomy or pharmacologic cytoreduction is recommended in combination with low-dose acetylsalicylic acid. Stringent cytoreduction is required for effective risk reduction. However, in recent reports, the rate of thromboembolic complications in PV patients under cytoreductive therapy appears still elevated compared to healthy individuals. This study reports on a chart review to assess for cytoreductive therapy of 1440 PV patients in real life. Methods Forty-two eligible hematologists/oncologists in private practice treating patients with MPN were recruited to participate in a paper–pencil-based survey conducted between January 2019 and March 2020 in Germany. Physicians were asked to report primary documented data obtained from patient charts. Descriptive analyses were conducted to assess for patient characteristics, treatment modalities, risk factors and thromboembolic complications. Results Data were collected from the patient charts of 1440 individuals diagnosed with PV. The patient population was older than those reported in multicenter trials with a median age of 72.2 years at the time of reporting and 63.5 years at diagnosis. Age was the main factor accounting for high-risk status with 84.7% of patients being above the age of 60 followed by thromboembolic complications reported in 21.3% of patients. The use of pharmacologic cytoreduction was highly variable between participating centers with an average of 60.7% and a range of 10.1–100%. Hydroxyurea was the most frequently used drug followed by ruxolitinib, while interferons were reported for a minority of patients. For 35.4% of patients a persistent need for phlebotomy in addition to cytoreductive treatment was reported. Although presence of high-risk criteria and insufficient disease control were reported as main triggers to initiate pharmacologic cytoreduction, 28.1% had elevated hematocrit values (> 45%) and 38.6% showed persistence of elevated leukocyte count (> 109/l) while on cytoreductive treatment. In contrast, physician-reported symptom burden was lower than published in clinical trials and patient-reported outcomes. The rate of patients experiencing thromboembolic complications was 32.2% at any time and 14.3% after diagnosis with most patients receiving acetylsalicylic acid and 10.8% remaining on oral anticoagulants or heparin. Conclusions Cytoreductive treatment of high-risk PV in real life is highly variable regarding indication for cytoreduction and definition of therapy resistance. This study highlights the need for (i) improved risk stratification for thromboembolic events, (ii) consequent indication of pharmacologic cytoreduction in high-risk PV and (iii) attention to signs of therapy resistance that can trigger an earlier and stringent switch to second line agents.

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“…However, whether comorbidities also affect the rate of progression in MPN patients is largely unknown. Interestingly, one study found that a higher body mass index (BMI ≥ 25) was associated with a lower probability of progression to pPV-MF and improved survival [ 59 ]. The authors speculate that normal weight or underweight may be due to a hypercatabolic state that can be associated with disease progression [ 60 ].…”

Section: Etiology Of Mpn Progressionmentioning

confidence: 99%

Progression of Myeloproliferative Neoplasms (MPN): Diagnostic and Therapeutic Perspectives

Baumeister

Chatain

Sofias

et al. 2021

Cells

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Classical BCR-ABL-negative myeloproliferative neoplasms (MPN) are a heterogeneous group of hematologic malignancies, including essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), as well as post-PV-MF and post-ET-MF. Progression to more symptomatic disease, such as overt MF or acute leukemia, represents one of the major causes of morbidity and mortality. There are clinically evident but also subclinical types of MPN progression. Clinically evident progression includes evolution from ET to PV, ET to post-ET-MF, PV to post-PV-MF, or pre-PMF to overt PMF, and transformation of any of these subtypes to myelodysplastic neoplasms or acute leukemia. Thrombosis, major hemorrhage, severe infections, or increasing symptom burden (e.g., pruritus, night sweats) may herald progression. Subclinical types of progression may include increases in the extent of bone marrow fibrosis, increases of driver gene mutational allele burden, and clonal evolution. The underlying causes of MPN progression are diverse and can be attributed to genetic alterations and chronic inflammation. Particularly, bystander mutations in genes encoding epigenetic regulators or splicing factors were associated with progression. Finally, comorbidities such as systemic inflammation, cardiovascular diseases, and organ fibrosis may augment the risk of progression. The aim of this review was to discuss types and mechanisms of MPN progression and how their knowledge might improve risk stratification and therapeutic intervention. In view of these aspects, we discuss the potential benefits of early diagnosis using molecular and functional imaging and exploitable therapeutic strategies that may prevent progression, but also highlight current challenges and methodological pitfalls.

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Impact of comorbidities and body mass index on the outcome of polycythemia vera patients

Cited by 12 publications

References 37 publications

Covert Brain Infarcts in Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders

Covert Brain Infarcts in Patients with Philadelphia Chromosome-Negative Myeloproliferative Disorders

Cytoreductive treatment in real life: a chart review analysis on 1440 patients with polycythemia vera

Progression of Myeloproliferative Neoplasms (MPN): Diagnostic and Therapeutic Perspectives

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