Imelda Marton

Stroke in essential thrombocythemia

BACKGROUND Our aim was to assess the incidence and the special characteristics of stroke, as a severe complication of patients diagnosed with essential thrombocythemia (ET). METHODS A retrospective analysis was carried out on 102 patients with ET enrolled and analyzed from the period between 1999 and 2012. Patients with one or more strokes were selected. The characteristics of stroke events, the medication, and the median platelet counts were revised. RESULTS One or more stroke events were revealed in 11 cases (4 males and 7 females) with a median age of 67 years [range: 45-82 years]. The median platelet count at hematological diagnosis was 658×10(9)/L [range: 514-1157×10(9)/L], while during the time of stroke it was 450×10(9)/L [range: 320-885×10(9)/L]. The median follow-up of the patients with stroke was 60 months [range: 19-127 months]. At the time of the stroke, almost all the patients (8/11 cases, 73%) were already on anti-platelet therapy, alone or in combination with cytoreductive therapy (e.g. hydroxyurea). Brain imaging modalities in most cases demonstrated periventricular and/or subcortical and/or basal ganglia lacunes or confluent chronic white matter ischemic lesions in all cerebral arterial regions. Most patients (9/11; 82%) presented at least two serious conventional vascular risk factors, which may have influenced both the clinical course and the morphologic alterations. No correlation was found between the platelet count and the occurrence of stroke. CONCLUSION Our findings lead us to suppose that ET may be regarded as a risk factor for stroke (mainly of ischemic, small-vessel type), and the early diagnosis and the personalized management of the patients global vascular risk in the treatment of ET may promote the prevention of further cerebrovascular events.

Characterization of left atrial dysfunction in hypereosinophilic syndrome – Insights from the Motion analysis of the heart and great vessels by three-dimensional speckle tracking echocardiography in pathological cases (MAGYAR-Path) Study

INTRODUCTION The present study was designed to compare three-dimensional speckle tracking echocardiography (3DSTE)-derived left atrial (LA) volumetric, volume-based functional and strain parameters between patients with hypereosinophilic syndrome (HES) and matched controls. METHODS A total of 10 HES patients and 19 age- and gender-matched healthy controls were included in the study. Complete two-dimensional Doppler echocardiography and 3DSTE were performed in all HES cases and controls. RESULTS Significantly increased maximum (72.9±38.8 ml vs. 45.6±15.5 ml, p=0.01) and minimum (46.3±33.3 ml vs. 26.0±15.0 ml, p=0.03) LA volumes and LA volume before atrial contraction (62.0±36.0 ml vs. 36.5±16.6 ml, p=0.01) were found in HES patients compared to controls. Both peak global (18.3±6.7% vs. 25.6±9.0%, p=0.03) and mean segmental (22.2±6.0% vs. 31.0±12.1%, p=0.04) circumferential strains were significantly reduced in HES patients, suggesting decreased LA reservoir function. CONCLUSION Increased LA volumes can be demonstrated in HES patients, accompanied by reduced LA peak circumferential strain as assessed by 3DSTE, suggesting LA remodeling.

Myocardial infarction as a thrombotic complication of essential thrombocythemia and polycythemia vera

Objective: Detailed analyses of clinical characteristics of myocardial infarction (MI) as an essential thrombocythemia (ET)- and polycythemia vera (PV)-related complication have been so far presented mostly as case reports. Therefore, the aim of this retrospective analysis was to evaluate the main cardiological and hematological characteristics for better understanding myocardial complications in ET/PV. Methods: A retrospective analysis was carried out involving 263 patients diagnosed with ET or PV (155/108) between 1998 and 2014. Fourteen patients suffered MI during the hematological follow-up. Their clinical characteristics were compared to 162 patients (97 ET and 65 PV patients) who did not exhibit any major thrombotic complications (MI, stroke/transient ischemic attack, and venous events) before or after hematological diagnosis of ET/PV. Results: Fourteen MI events occurred among the 263 patients (5.3%). Vascular risk factors were found in 92.9% (13/14) of analyzed cases. In all, 71.4% of the MI complications developed within 12 months after the diagnosis of ET/PV. The coronary angiography findings revealed ST-elevation MI in four cases and non-ST-elevation MI in 10. Significant stenosis of coronary arteries requiring percutaneous coronary intervention with a stent implantation was present in seven cases, while three had complex stenoses or previous grafts/stents. All of them had undergone coronary artery bypass graft operations. Conclusion: The results of the present study suggest that early detection and consideration of individual management of vascular risk factors in ET/PV patients are also important. Furthermore, a better theoretic understanding of platelet activation and role of leukocytes in myeloproliferative neoplasm-related thrombosis could open new perspectives in thrombosis prediction and prevention.

Thrombotic events and importance of IPSET thrombosis risk evaluation score in essential thrombocythaemia

INTRODUCTION Thrombo-haemorrhagic complications contribute to both morbidity and mortality in patients with essential thrombocythaemia. AIM The aim of the authors was to estimate the incidence of thrombotic events and to examine the clinical utility of IPSET thrombosis risk evaluation score against conventional two-categorical (low and high) risk assessment. METHOD A retrospective analysis was carried out on 155 patients with essential thrombocythaemia (106 females; median age, 61 years) in a period between 1999 and 2014. RESULTS The analysis revealed 55 (35.5%) major thrombotic events before and 25 (16.1%) major thrombotic complications after establishment of the haematologic diagnosis. Significant differences were observed in thrombosis-free survival between the different IPSET groups (p = 0.002). CONCLUSIONS The IPSET model was first examined in this cohort of patients with essential thrombocythaemia diagnosed in a single Hungarian haematologic centre. The results suggest that this score may provide more information than the conventional thrombosis risk assessment.

Quantitative assessment of JAK2 V617F and CALR mutations in Philadelphia negative myeloproliferative neoplasms

BACKGROUND Philadelphia negative myeloproliferative neoplasms (MPNs) are characterized by frequent mutations of driver genes including JAK2, CALR and MPL. While the influence of JAK2 V617F mutant allele burden on the clinical phenotype of MPN patients is well-described, the impact of CALR mutant allele burden on clinical features needs further investigation. PATIENTS AND METHODS Quantitative assessment of JAK2 and CALR mutations was performed on diagnostic DNA samples from 425 essential thrombocythemia (ET) and 227 primary myelofibrosis patients using real-time quantitative PCR and fragment length analysis. Characterization of CALR mutations and detection of MPL mutations were performed by Sanger sequencing. RESULTS Twelve novel CALR mutations have been identified. ET patients with CALRmut load exceeding the median value exhibited lower hemoglobin values (12.0 vs. 13.6 g/dL), higher LDH levels (510 vs. 351 IU/L) and higher rate of myelofibrotic transformation (19% vs. 5%). The CALRmut load was higher among ET patients presenting with splenomegaly compared to those without splenomegaly (50.0% vs. 43.5%). CONCLUSION Our study confirms the clinical significance of driver mutational status and JAK2mut load in MPNs; in addition, unravels a novel clinical association between high CALRmut load and a more proliferative phenotype in ET.

Új kezelési lehetőség – új probléma? Miért interferál a daratumumab a vércsoport-szerológiai vizsgálatokkal?

Absztrakt: A szerzők harom, daratumumabkezelt, myeloma multiplexben szenvedő beteg eseten keresztul mutatjak be a daratumumab okozta interferenciat a vercsoport-szerologiai vizsgalatokban, melynek ...

Aortic stiffness is increased in patients with hypereosinophilic syndrome being in early necrotic phase

Background Persistent eosinophilia and eosinophil-mediated single- or multiple-organ damage are typical features of hypereosinophilic syndrome (HES). Theoretically, eosinophilic infiltration of the ascending aortic wall could not be excluded in HES, therefore the present study aimed to test whether HES is associated with abnormalities in aortic elastic properties. Methods The present study comprised 10 HES patients (mean age: 57.6±10.1 years, 5 males) without known cardiovascular disease, their results were compared to 19 age-, gender- and risk factor-matched controls (59.2±4.2 years, 15 males). Complete two-dimensional Doppler echocardiography with measurement of echocardiographic aortic elastic properties was performed in all HES cases and controls. Results Although neither systolic (30.6±3.4 vs. 30.1±3.6 mm, P=ns), nor diastolic (28.7±3.6 vs. 27.8±3.2 mm, P=ns) aortic diameter differed significantly between HES patients and matched controls, significantly increased aortic stiffness index (11.19±5.65 vs. 7.04±2.97, P<0.05) could be demonstrated in HES patients. Conclusions Increased aortic stiffness could be demonstrated in HES patients in their early necrotic phase.

Cerebrovascular Complications and Polycythaemia Vera

Polycythaemia vera (PV) is a stem cell-derived myeloid haematologic malignancy. It is characterized by an expansion of one or more haematopoietic cell lineages, resulting in increased mature blood components in the peripheral blood. The disease features include erythrocytosis, leukocytosis and/or thrombocytosis, as a consequence of which PV may exhibit a unique prothrombic state [1, 2]. There is a possibility of progression into acute myeloid leukaemia or myelofibrosis, the 10-year risk ranging between 3% and 10%, but the life expectancy of patients with PV is commonly affected by thrombo-haemorrhagic events, with a reported incidence of 12–39% [1, 3]. The clinical manifestations of the thrombotic events in PV patients may vary from mild microvascular circulatory disturbances (e.g. erythromelalgia, tinnitus or vertigo) to more severe complications, such as migraine-like cerebral transient ischaemic attacks, transient ischaemic attacks, ischaemic stroke, myocardial infarction or venous thrombosis (e.g. cerebral sinus and venous thrombosis or deep venous thrombosis). Information relating to the association of PV and cerebrovascular complications such as stroke and transient ischaemic attacks from detailed clinical aspects are limited in the relevant literature [4–7]. The aim of our retrospective analysis was to assess the frequency and the main characteristics of the cerebrovascular complications of patients diagnosed with PV, with a view to describing typical neuroradiological lesions characteristic of PV.

Nasalis típusú extranodalis natural killer T-sejtes lymphoma hazai előfordulása és kezelésével szerzett tapasztalatok

INTRODUCTION Extranodal natural killer/T (NK/T) cell lymphoma, nasal type (ENKTL) represents a rare subtype of T-cell lymphomas with aggressive clinical behavior according to WHO 2016 classification. AIM ENKTL has distinctive geographic distribution with higher incidence in Asia and Latin America (10% of all non-Hodgkin lymphoma cases), than in Europe and North America (<1%). ENKTL tipically origins from nasopharynx and upper aerodigestive tract. Anthracycline-based chemotherapy regimens are largely ineffective in the treatment of ENKTL. METHOD Our aims were to evaluate the incidence and treatment strategies of ENKTL patients in Hungarian Haematological Centres between 2003 and 2015. Altogether 20 patients with ENKTL were treated in the 4 haematological hospitals (male:female ratio 12:8, with median 49.5 years of age). RESULTS Ten patients had localized (stage I-II) disease at the time of the diagnosis. Seventeen patients were treated with chemotherapy (11/CHOP, CHOP-like, 2/HyperCVAD, 1/ProMACECytaBom, 1/SMILE, 2/others), which was completed with involved-field radiation therapy (IFRT) (40-46 Gy) in 6 cases were used. After first-line therapy 9 patients achieved complete remission (CR), 3 patients had partial remission (PR), 3 patients had progressive disease (PD), and 2 patients had stable disease (SD). Median follow-up was 32 (3-113) months. Five patients received second-line therapy for progressive or recurrent disease [2/DHAP, 1/VIM, 1/HyperCVAD, 1/ProMACECytaBom]. None of the patients achieved CR after second-line therapy. Two patients have undergone autologous hematopoietic stem cell transplantation (HSCT) after the first CR. CONCLUSION ENKTL treatment is more effective with nonanthracycline-containing regimens. L-asparaginase containing chemotherapy and concurrent or sequential chemo-radiotherapy improves survival and CR rates. Orv Hetil. 2017; 158(41): 1635-1641.Absztrakt: Bevezetes: Az extranodalis nasalis tipusu natural killer/T (NK/T) sejtes lymphoma (ENKTL) a T-sejtes lymphomak egyik ritka agressziv megjelenesű formaja, amely elsősorban sinonasalis es nasopharynx kiindulasu. Bar előfordulasa ritka a fejlett nyugati orszagokban, kezelese a hagyomanyos, agressziv lymphomakban alkalmazott antraciklintartalmu kemoterapiaval csekely hatekonysagu. Celkitűzes: ENKTL-esetek előfordulasa hazai hematologiai centrumok altal gondozott non-Hodgkin-lymphomas betegek kozott. Modszer: A szerzők negy magyarorszagi hematologiai centrumban 2003–2015 kozott kezelt 20 ENKTL-beteg klinikai adatait elemeztek. A betegek kozott 12 ferfi es 8 nő volt, median eletkor 49,5 ev (22–84 ev). Eredmenyek: Tiz esetben a betegseg lokalizalt (I–II. stadiumban) volt a diagnozis idejen. Kemoterapias kezelesben reszesult 17 beteg (11 CHOP, CHOP-szerű, kettő hyper-CVAD, egy ProMACECytaBom, egy SMILE, kettő egyeb), amelyet hat esetben erintett mezős besugarzassal (IFRT) egeszitettek ki (40–46 Gy). Az...

Original ArticleCharacterization of left atrial dysfunction in hypereosinophilic syndrome – Insights from the Motion analysis of the heart and great vessels by three-dimensional speckle tracking echocardiography in pathological cases (MAGYAR-Path) StudyCaracterização da disfunção auricular esquerda na síndrome hipereosinofílica – visão da análise de movimentos do coração e dos grandes vasos por ecocardiografia tridimensional speckle tracking em casos patológicos – estudo MAGYAR-Path

Introduction The present study was designed to compare three-dimensional speckle tracking echocardiography (3DSTE)-derived left atrial (LA) volumetric, volume-based functional and strain parameters between patients with hypereosinophilic syndrome (HES) and matched controls.