scholarly journals Bone Marrow Soluble Mediator Signatures of Patients With Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

2021 ◽  
Vol 11 ◽  
Author(s):  
Juçara Gastaldi Cominal ◽  
Maira da Costa Cacemiro ◽  
Maria Gabriela Berzoti-Coelho ◽  
Illy Enne Gomes Pereira ◽  
Fabiani Gai Frantz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Driver Mutations ◽  
Vascular Events ◽  
Laboratory Parameters ◽  
Inflammatory Status ◽  
Bm Niche ◽  
Soluble Mediator

BackgroundEssential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are clonal hematological diseases classified as Philadelphia chromosome-negative myeloproliferative neoplasms (MPN). MPN pathogenesis is associated with the presence of somatic driver mutations, bone marrow (BM) niche alterations, and tumor inflammatory status. The relevance of soluble mediators in the pathogenesis of MPN led us to analyze the levels of cytokines, chemokines, and growth factors related to inflammation, angiogenesis and hematopoiesis regulation in the BM niche of MPN patients.MethodsSoluble mediator levels in BM plasma samples from 17 healthy subjects, 28 ET, 19 PV, and 16 PMF patients were determined using a multiplex assay. Soluble mediator signatures were created from categorical analyses of high mediator producers. Soluble mediator connections and the correlation between plasma levels and clinic-laboratory parameters were also analyzed.ResultsThe soluble mediator signatures of the BM niche of PV patients revealed a highly inflammatory and pro-angiogenic milieu, with increased levels of chemokines (CCL2, CCL5, CXCL8, CXCL12, CXCL10), and growth factors (GM-CSF M-CSF, HGF, IFN-γ, IL-1β, IL-6Ra, IL-12, IL-17, IL-18, TNF-α, VEGF, and VEGF-R2). ET and PMF patients presented intermediate inflammatory and pro-angiogenic profiles. Deregulation of soluble mediators was associated with some clinic-laboratory parameters of MPN patients, including vascular events, treatment status, risk stratification of disease, hemoglobin concentration, hematocrit, and red blood cell count.ConclusionsEach MPN subtype exhibits a distinct soluble mediator signature. Deregulated production of BM soluble mediators may contribute to MPN pathogenesis and BM niche modification, provides pro-tumor stimuli, and is a potential target for future therapies.

scholarly journals Cytokine Consistency Between Bone Marrow and Peripheral Blood in Patients With Philadelphia-Negative Myeloproliferative Neoplasms

2021 ◽  
Vol 8 ◽  
Author(s):  
Pu Chen ◽  
Boting Wu ◽  
Lili Ji ◽  
Yanxia Zhan ◽  
Feng Li ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Inflammatory Cytokines ◽  
Peripheral Blood ◽  
Myeloproliferative Neoplasms ◽  
Critical Role ◽  
Primary Myelofibrosis ◽  
Diagnostic Value ◽  
Inflammatory Status ◽  
Bm Niche ◽  
Cytokine Levels

Background: Inflammation might play a critical role in the pathogenesis and progression of Philadelphia-negative myeloproliferative neoplasms (Ph−MPNs) with elevated inflammatory cytokines in peripheral blood (PB). However, the inflammatory status inside the bone marrow (BM), which is the place of malignancy origin and important microenvironment of neoplasm evolution, has not yet been elucidated.Methods: Inflammatory cytokine profiles in PB and BM of 24 Ph-MPNs patients were measured by a multiplex quantitative inflammation array. Cytokines that correlated between PB and BM were selected and then validated by ELISA in a separate cohort of 52 MPN patients. Furthermore, a panel of cytokines was identified and examined for potential application as non-invasive markers for the diagnosis and prediction of fibrosis progress of MPN subtypes.Results: The levels of G-CSF, I-309, IL-1β, IL-1ra, IL-12p40, IL-15, IL-16, M-CSF, MIG, PDGF-BB, and TIMP-1 in BM supernatants were significantly higher than those in PB (all p < 0.05). Linear correlations between BM and PB levels were found in 13 cytokines, including BLC, Eotaxin-2, I-309, sICAM-1, IL-15, M-CSF, MIP-1α, MIP-1δ, RANTES, TIMP-1, TIMP-2, sTNFRI, and sTNFRII (all R > 0.4 and p < 0.05). Levels of BLC, Eotaxin-2, M-CSF, and TIMP-1 in PB were significantly different from those in health controls (all p < 0.05). In PB, levels of TIMP-1 and Eotaxin-2 in essential thrombocythemia (ET) group were significantly lower than those in groups of prefibrotic primary myelofibrosis (pre-PMF) [TIMP-1: 685.2 (322.2–1,229) ng/ml vs. 1,369 (1,175–1,497) ng/ml, p = 0.0221; Eotaxin-2: 531.4 (317.9–756.6) pg/ml vs. 942.4 (699.3–1,474) pg/ml, p = 0.0393] and primary myelofibrosis (PMF) [TIMP-1: 685.2 (322.2–1229) ng/ml vs. 1,365 (1,115–1,681) ng/ml, p = 0.0043; Eotaxin-2: 531.4 (317.9–756.6) pg/ml vs. 1,010 (818–1,556) pg/ml, p = 0.0030]. The level of TIMP-1 in myelofibrosis (MF) >1 group was significantly higher than that in MF ≤ 1 group.Conclusion: Abnormal inflammatory status is present in MPN, especially in its BM microenvironment. Consistency between PB and BM levels was found in multiple inflammatory cytokines. Circulating cytokine levels of BLC, M-CSF, Eotaxin-2, and TIMP-1 reflected inflammation inside BM niche, suggesting potential diagnostic value for MPN subtypes and prognostic value for fibrosis progression.

Current Concepts of Pathogenesis and Treatment of Philadelphia Chromosome-Negative Myeloproliferative Neoplasms

2021 ◽  
Vol 41 (03) ◽  
pp. 197-205
Author(s):  
Franziska C. Zeeh ◽  
Sara C. Meyer
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Mutational Analysis ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Standard Of Care ◽  
Driver Mutations ◽  
Hematopoietic Stem ◽  
Therapeutic Decisions ◽  
Jak2 Inhibitors

AbstractPhiladelphia chromosome-negative myeloproliferative neoplasms are hematopoietic stem cell disorders characterized by dysregulated proliferation of mature myeloid blood cells. They can present as polycythemia vera, essential thrombocythemia, or myelofibrosis and are characterized by constitutive activation of JAK2 signaling. They share a propensity for thrombo-hemorrhagic complications and the risk of progression to acute myeloid leukemia. Attention has also been drawn to JAK2 mutant clonal hematopoiesis of indeterminate potential as a possible precursor state of MPN. Insight into the pathogenesis as well as options for the treatment of MPN has increased in the last years thanks to modern sequencing technologies and functional studies. Mutational analysis provides information on the oncogenic driver mutations in JAK2, CALR, or MPL in the majority of MPN patients. In addition, molecular markers enable more detailed prognostication and provide guidance for therapeutic decisions. While JAK2 inhibitors represent a standard of care for MF and resistant/refractory PV, allogeneic hematopoietic stem cell transplantation remains the only therapy with a curative potential in MPN so far but is reserved to a subset of patients. Thus, novel concepts for therapy are an important need, particularly in MF. Novel JAK2 inhibitors, combination therapy approaches with ruxolitinib, as well as therapeutic approaches addressing new molecular targets are in development. Current standards and recent advantages are discussed in this review.

scholarly journals Clonal Hematopoiesis and Mutations of Myeloproliferative Neoplasms

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2100
Author(s):  
Lasse Kjær
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Clinical Intervention ◽  
Driver Mutation ◽  
Response Monitoring ◽  
Driver Mutations ◽  
Clonal Hematopoiesis ◽  
Disease Biology ◽  
Background Population ◽  
The Impact

Myeloproliferative neoplasms (MPNs) are associated with the fewest number of mutations among known cancers. The mutations propelling these malignancies are phenotypic drivers providing an important implement for diagnosis, treatment response monitoring, and gaining insight into the disease biology. The phenotypic drivers of Philadelphia chromosome negative MPN include mutations in JAK2, CALR, and MPL. The most prevalent driver mutation JAK2V617F can cause disease entities such as essential thrombocythemia (ET) and polycythemia vera (PV). The divergent development is considered to be influenced by the acquisition order of the phenotypic driver mutation relative to other MPN-related mutations such as TET2 and DNMT3A. Advances in molecular biology revealed emergence of clonal hematopoiesis (CH) to be inevitable with aging and associated with risk factors beyond the development of blood cancers. In addition to its well-established role in thrombosis, the JAK2V617F mutation is particularly connected to the risk of developing cardiovascular disease (CVD), a pertinent issue, as deep molecular screening has revealed the prevalence of the mutation to be much higher in the background population than previously anticipated. Recent findings suggest a profound under-diagnosis of MPNs, and considering the impact of CVD on society, this calls for early detection of phenotypic driver mutations and clinical intervention.

Increased expression of vascular endothelial growth factor receptor 1 correlates with VEGF and microvessel density in Philadelphia chromosome-negative myeloproliferative neoplasms

2011 ◽  
Vol 64 (3) ◽  
pp. 226-231 ◽  
Author(s):  
Leonardo Boiocchi ◽  
Claudia Vener ◽  
Federica Savi ◽  
Emanuela Bonoldi ◽  
Alessia Moro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Microvessel Density ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Endothelial Growth Factor

AimsThe authors investigated vascular endothelial growth factor receptor 1 (VEGFR-1) protein expression in a series of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPNs) and its correlations with microvessel density (MVD) and vascular endothelial growth factor (VEGF).Methods83 bone marrow biopsies of Ph- MPNs patients, including 27 essential thrombocythaemia (ET), 21 polycythaemia vera (PV) and 35 primary myelofibrosis (PMF), and 10 normal controls (NCs) were investigated by immunohistochemistry.ResultsPatients with PV and PMF showed an increased MVD (PV: 20.1±10.6; PMF: 25.8±6.5) compared with those with ET or NCs (ET: 10.4±4.6; NCs: 7±3.4). VEGFR-1 expression was increased in Ph- MPNs, particularly in PV and PMF (NCs: 0.07±0.03; ET: 0.15±0.09; PV: 0.31±0.2; PMF: 0.31±0.04). VEGF expression parallelled VEGFR-1 and resulted increased in Ph- MPNs (NCs: 0.08±0.04; ET: 0.13±0.06; PV: 0.29±0.2; PMF: 0.31±0.15) and higher in post-polycythaemic myelofibrosis and in the fibrotic stage of PMF than in the non-fibrotic phases of both diseases. VEGFR-1 protein expression correlated with MVD and VEGF expression in Ph- MPNs. VEGFR-1 and VEGF were expressed by the same bone marrow populations: megakaryocytes, macrophages and immature myeloid precursors showed a moderate to strong immunostaining intensity in both Ph- MPNs and NCs. The erythroid precursors were not immunoreactive.ConclusionsVEGFR-1 and VEGF were increased and co-localised in megakaryocytes, macrophages and myeloid precursors of Ph- MPNs. This finding supports the hypothesis of a VEGF/VEGFR-1 autocrine loop in the neoplastic cells of Ph- MPNs.

Chronic Myeloid Leukemia: Clinical and Laboratory Features At Presentation To a Referral Hospital In Southern Nigeria

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5174-5174 ◽  
Author(s):  
Kaladada I. Korubo ◽  
Hannah Emmanuel Omunakwe ◽  
Chijioke A. Nwauche
Keyword(s):  
Bone Marrow ◽  
Retrospective Study ◽  
Clinical Features ◽  
Blood Count ◽  
Bone Marrow Aspirate ◽  
Philadelphia Chromosome ◽  
Molecular Techniques ◽  
Full Blood Count ◽  
Laboratory Parameters ◽  
Wbc Count

Abstract Background Chronic Myeloid Leukaemia (CML) is one of the commonly diagnosed leukaemias and has been extensively studied, making it the first malignancy to have a constant identified mutation present which is relevant for diagnosis. CML is also a model for targeted therapy in the treatment of cancer. Before the development of molecular techniques in diagnosis of CML, the clinical and laboratory parameters which included spleen size, total white blood cell (WBC) count, peripheral and bone marrow smears were essential in making a diagnosis of CML. In a developing country with less availability of molecular techniques of diagnosis, these parameters are still invaluable. Here we present an eight year retrospective study of patients who were diagnosed with CML in our center, which is a tertiary referral center in the Niger-Delta zone of Nigeria. Methods We carried out a retrospective study of all CML cases who presented to the department of hematology at the University of Port Harcourt Teaching Hospital, Nigeria, from the year July 2004 – June 2012. Data were extracted from patients' records and included age, sex, absence/presence & duration of symptoms, full blood count and presence of Philadelphia chromosome. Other investigations done were erythrocyte sedimentation rate, uric acid, renal and liver function tests. Diagnosis of CML was made based on clinical features, full blood count, bone marrow aspirate and karyotyping for Philadelphia chromosome where available. The data generated from the above information were analyzed with SPSS statistical package software with results expressed in statistical tables. Results A total of 105 haematological malignancies were seen between July 2004 and June 2012 of which 34 (32.4%) were CML. The mean age of presentation was 32.4 ± 16.2 years (range 19 - 75 years, median 36.5 years). There were 18 males and 16 females. The males had a lower mean age than the females (37.3 vs. 40.4 years) but this was not statistically significant (p=0.59), however the median age of males and females were the same (36 vs. 36.5 years). Males were only slightly more affected than females (male, female ratio 1.1 : 1). No patient was asymptomatic at presentation. The commonest presenting clinical features were splenomegaly (91.2%), anemia (61.8%), fever (50%) and weight loss (50%). One patient had undergone a splenectomy. Seven (20.6%) presented as incidental findings while being investigated for other reasons due to development of complications such as renal failure, hearing loss, priapism, and had a higher mean WBC of 535.7 X 109/L. All the patients presented with leucocytosis (mean 287 X 109/L, range 72-1343 X 109/L). There was no case of thrombocytopenia, but nine (26.5%) had thrombocytosis with a mean platelet count of 639.1 X 109/L. Nineteen (55.9%) had a raised ESR. Bone marrow aspirate findings of all patients typically showed increased cellularity and marked myeloid hyperplasia. Of the total 34 CML patients, 3(8.8%) presented in the accelerated phase and only 1(2.9%) in the blastic phase, majority presented in the chronic phase. Karyotyping for Philadelphia chromosome was done for 12(35.3%) and was positive in all cases. Conclusion CML represented about a third of the haematological cancers seen at our center. Our median age of presentation is lower than Caucasian values (32.4 vs ∼60 years) as reported by other African literature. The males presented at an earlier age than the women although this was not statistically significant. The clinical and laboratory parameters are comparable to international studies, though our patients had very high WBC count at presentation. We did not have any asymptomatic patient. This may be attributed to lack of awareness on the importance of routine medical checkup and evaluation in low resource countries. However, a larger multi-center study is required to corroborate these findings. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Complex molecular genetic diagnostic algorithm in the diagnosis of myeloproliferative neoplasms

2014 ◽  
Vol 155 (52) ◽  
pp. 2074-2081 ◽  
Author(s):  
Tünde Krähling ◽  
Katalin Balassa ◽  
Nóra Meggyesi ◽  
András Bors ◽  
Judit Csomor ◽  
...  
Keyword(s):  
Triple Negative ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Molecular Techniques ◽  
Janus Kinase ◽  
Driver Mutations ◽  
Similar Distribution ◽  
Janus Kinase 2 ◽  
Chain Reactions ◽  
Thrombopoietin Receptor

Introduction: Mutations in Janus kinase 2, calreticulin and thrombopoietin receptor genes have been identified in the genetic background of Philadelphia chromosome negative, “classic” myeloproliferative neoplasms. Aim: The aim of the authors was to identify driver mutations in a large myeloproliferative cohort of 949 patients. Method: A complex array of molecular techniques (qualitative and quantitative allele-specific polymerase chain reactions, fragment analyzes, high resolution melting and Sanger sequencing) was applied. Results: All 354 patients with polycythemia vera carried Janus kinase 2 mutations (V617F 98.6%, exon 12: 1.4%). In essential thrombocythemia (n = 468), the frequency of V617F was 61.3% (n = 287), that of calreticulin 25.2% (n = 118), and that of thrombopoietin receptor mutations 2.1% (n = 10), while 11.3% (n = 53) were triple-negative. Similar distribution was observed in primary myelofibrosis (n = 127): 58.3% (n = 74) V617F, 23.6% (n = 30) calreticulin, 6.3% (n = 8) thrombopoietin receptor mutation positive and 11.8% (n = 15) triple-negative. Conclusions: The recent discovery of calreticulin gene mutations led to definite molecular diagnostics in around 90% of clonal myeloproliferative cases. Orv. Hetil., 2014, 155(52), 2074–2081.

scholarly journals The possible role of mutated endothelial cells in myeloproliferative neoplasms

Haematologica ◽  
2021 ◽  
Author(s):  
Mirko Farina ◽  
Domenico Russo ◽  
Ronald Hoffman
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Hematopoietic Cells ◽  
Clinical Manifestations ◽  
Vascular Complications ◽  
Hematologic Malignancies ◽  
Driver Mutations ◽  
Vascular Events ◽  
Hematopoietic Stem ◽  
High Incidence

Myeloproliferative neoplasms (MPN) are chronic, clonal hematologic malignancies characterized by myeloproliferation and a high incidence of vascular complications (thrombotic and bleeding). Although MPN-specific driver mutations have been identified, the underlying events that culminate in these clinical manifestations require further clarification. We reviewed the numerous studies performed during the last decade identifying endothelial cell (EC) dysregulation as a factor contributing to MPN disease development. The JAK2V617F MPN mutation and other myeloid-associated mutations have been detected not only in hematopoietic cells but also in EC and their precursors in MPN patients, suggesting a link between mutated EC and the high incidence of vascular events. To date, however, the role of EC in MPN continues to be questioned by some investigators. In order to further clarify the role of EC in MPN, we first describe the experimental strategies used to study EC biology and then analyze the available evidence generated using these assays which implicate mutated EC in MPN-associated abnormalities. Mutated EC have been reported to possess a pro-adhesive phenotype as a result of increased endothelial Pselectin exposure, secondary to degranulation of Weibel-Palade bodies, which is further accentuated by exposure to pro-inflammatory cytokines. Additional evidence indicates that MPN myeloproliferation requires JAK2V617F expression by both hematopoietic stem cells and EC. Furthermore, the reports of JAK2V617F and other myeloid malignancy- associated mutations in both hematopoietic cells and EC in MPN patients support the hypothesis that MPN driver mutations may first appear in a common precursor cell for both EC and hematopoietic cells.

scholarly journals Prefibrotic Myelofibrosis Presenting with Multiple Cerebral Embolic Infarcts and the Rare MPL W515S Mutation

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Stephen E. Langabeer ◽  
Lisa Lee Tokar ◽  
Laura Kearney ◽  
Cathal O’Brien ◽  
Kowshika Thavarajah ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloproliferative Neoplasms ◽  
Primary Myelofibrosis ◽  
Driver Mutations ◽  
Common Mutation ◽  
Limited Information ◽  
Phenotypic Data ◽  
Activating Mutations ◽  
Cerebral Event

Acquired, activating mutations of MPL W515 are recognised driver mutations of the myeloproliferative neoplasms (MPN), namely, essential thrombocythemia and primary myelofibrosis. The most common mutation at this codon is W515L with several other mutations also described at a lower frequency. Of these less common mutations, MPL W515S has only been reported sporadically with limited information on clinicopathological associations. We describe the case of an elderly man with persistent thrombocytosis presenting with an ischemic cerebral event. Bone marrow biopsy showed evidence of prefibrotic myelofibrosis with targeted sequencing demonstrating the presence of the rare MPL W515S mutation. Thrombolytic and cytoreductive therapies resulted in a favorable outcome and follow-up. This case provides additional, necessary, and phenotypic data for the rare MPN-associated MPL W515S mutation.

Patients with myeloproliferative neoplasms (MPN) who later develop ph+ chronic myelogenous leukemia (CML): A case series.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18563-e18563
Author(s):  
Shahina Patel ◽  
Seo-Hyun Kim ◽  
Jamile M. Shammo ◽  
Jerald P. Radich ◽  
Howard R. Terebelo
Keyword(s):  
Lead Time ◽  
Chart Review ◽  
Myeloproliferative Neoplasms ◽  
Clonal Evolution ◽  
Philadelphia Chromosome ◽  
Case Series ◽  
Myelogenous Leukemia ◽  
Driver Mutations ◽  
Hematopoietic Stem ◽  
True Incidence

e18563 Background: Myeloproliferative Neoplasms are divided by the presence or absence of the Philadelphia Chromosome. Ph- MPN, typically possess driver mutations of JAK-2, MPL and CALR. CALR is involved with apoptosis and cell proliferation . MPL leads to TPO receptor stimulation and mutations are reported as a known cause of AA. JAK-2 mutations render hematopoietic stem cells more sensitive to growth. Though the true incidence is unknown, there are infrequent reports of pts with ET who later develop CML. CALR, MPL and JAK-2 mutations may have some further role in determining whether these are two separate events or clonally derived. We report three pts with MPN who later developed CML. Methods: Chart Review Results: Pt 1 had ET, diagnosed 21 yrs earlier treated with hydroxyurea. He then developed a rising WBC and platelets which necessitated a marrow which detected Ph+ CML. He was CALR positive. NGS was negative for nondriver mutations. Platelets initially declined from 3 million to 975K with TKI and he achieved a MMR. However, the inability to control his thrombocytosis required the addition of ruxolitinib. Pt 2 was diagnosed with ET and was treated with P32. Nine yrs later CML was diagnosed and TKI administration achieved a MMR. Subsequently, a profound anemia evaluation diagnosed PNH requiring eculizumab without benefit and repeat marrow with NGS revealed a MPLmutation and post-ET myelofibrosis. Pt 3 presented with a JAK-2 positive mutation and Polycythemia Vera. After four yrs of hydroxyurea extreme leukocytosis led to a marrow revealing a diagnosis of Ph+ CML. Dasatinib achieved a prompt MMR. NGS revealed KIT D618 V , coinciding with a diagnosis of systemic mastoytosis (SM). Conclusions: The rare observation of patients with both ET and CML have been reported by others with some recent implications of CALR as a common clone with double-mutant properties of CML. Our patients had a lead time of 21, 9, and 4 yrs, all having different mutations. Pts with MPN who develop unexplained leuko or thrombocytosis should be evaluated for CML.We plan to retrieve archival tissue to perform serial genetic analyses. Further work is required to determine whether these events are stochastic or represents clonal evolution.

Role of ethnicity in thrombotic and hemorrhagic complications of myeloproliferative neoplasms.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18555-e18555
Author(s):  
Andrew Peseski ◽  
Antoine Saliba ◽  
Hamid Sayar
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Previous History ◽  
Multivariate Logistic Regression Analysis ◽  
Vascular Complications ◽  
Bleeding Complications ◽  
Vascular Events ◽  
Hemorrhagic Complications ◽  
History Of ◽  
Caucasian Patients

e18555 Background: Philadelphia-chromosome negative myeloproliferative neoplasms (MPN) are a group of hematologic malignancies with known complications of hemorrhage and thrombosis. Age and a previous history of thrombosis are well-documented risk factors for future vascular events. Variations in the rates of these complications among ethnicities and sexes have not been extensively explored. Methods: Our retrospective analysis included 301 adult patients with a diagnosis of MPN without a history of thrombosis or hemorrhagic event seen at the Indiana University Simon Cancer Center between 1992 and 2019. Relationships between ethno-racial backgrounds and vascular complications and disease outcomes were evaluated using multivariate logistic regression analysis and Cox regression models. Results: Two hundred seventy-one patients (90.0%) were Caucasian and 30 patients (10.0%) were non-Caucasian. Non-Caucasian patients were comprised of African America, Asian, and Middle Eastern ethnicities. Median age at diagnosis was 56 years, and 43.9% were male. No association was found between the incidence of thrombotic complications and ethnicity using the log-rank test ( p 0.68). The incidence of hemorrhagic events was significantly increased in non-Caucasian patients (OR = 4.33; 95% CI [1.15 – 16.36], p 0.03). Patients with higher hemoglobin concentration at diagnosis were at a significantly lower risk of bleeding complications (OR = 0.79; 95% CI [0.65 – 0.95], p 0.01). Non-Caucasian patients were at 2.98 times (95% CI [1.19 – 7.44], p 0.02) higher risk when vascular complications were pooled together. Our models also showed that male sex (OR = 0.14; 95% CI [.02 – .98], p 0.048) and a higher platelet count at the time of diagnosis (OR = 0.99; 95% CI [.993 –.999], p 0.03) had a marginally significant association with decreased rate of progression to acute myeloid leukemia. Conclusions: This study suggests that in patients without a history of thrombosis or bleeding, non-Caucasian ethnicity was associated with an increased adjusted risk of hemorrhagic complications in patients with MPN. This observation may inform future studies to further characterize those disparities in outcomes at the genetic or socioeconomic level.

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