Péter Dombi

Efficacy of Romiplostim in the Treatment of Chemotherapy Induced Thrombocytopenia (CIT) in a Patient with Mantle Cell Lymphoma

Chemotherapy induced thrombopenia (CIT) is difficult to treat, as previous treatment options, including recombinant human thrombopoietin proved to be of limited efficacy. Here we report a case of a mantle cell lymphoma patient treated with intensive chemotherapy, who belongs to Yehova’s witnesses and therefore did not accept platelet transfusions. At the time of severe thrombocytopenia (zero thrombocytes/ per mikroliter) and gastrointestinal bleeding, on day 13 following the start of hyperCVAD B chemotherapy, romiplostim treatment was given resulting in quick normalisation of the platelet count followed by thrombocytosis. Based on our observation in further studies modification of the dose and timing of romiplostim injection in CIT should be considered.

Increased incidence of monoclonal B-cell infiltrate in chronic myeloproliferative disorders

A total of 106 trephine biopsy specimens with clinical, laboratory and pathology findings corresponding to chronic myeloproliferative disorders (CMPD) were analyzed to reveal the nature of the lymphoid infiltrate in the bone marrow. Histological investigation in 31 chronic myeloid leukemia (CML), 29 CMPDs not otherwise specified (CMPD-NOS), 28 essential thrombocytosis (ET), 15 polycythemia vera (PV) and three chronic eosinophilic leukemia/hypereosinophilic syndrome (CEL/HES) exhibited in 32% various amounts of lymphocytic infiltrate of sparsely to moderately diffuse or nodular types in the bone marrow, but the reactive or coinciding lymphomatous nature could not be revealed by histology alone in the majority of cases. PCR analysis of the immunoglobulin heavy chain (IgH) gene rearrangement was successfully performed in 81 out of the 106 DNA specimens extracted from formol–paraffin blocks. Out of the 81 samples with good-quality DNA, 18 gave a single or double discrete amplification band(s), which was reproducible only in four specimens. Sequencing finally proved monoclonal B-cell population of both pre- and postfollicular origin in all four samples (5%), one CML and three CMPD-NOS. Detailed clinical and pathological investigations indicated overt B-cell malignant lymphoma with clonal relationship to the CMPD in two out of these four patients. We conclude that detailed molecular analysis of IgH gene rearrangement in bone marrow samples of CMPD patients is needed to identify the true monoclonal B-cell infiltration, which—even without overt malignant lymphoma—may occur in this group of disorders.

Thromboembolic Events in Polycythaemia Vera Patients:An Audit of the Hungarian Philadelphia Negative Chronic Myeloproliferative Neoplasia Register

Objective: The Hungarian National Registry for Philadelphia chromosome negative myeloproliferative neoplasms was used to assess the clinical characteristics of Hungarian patients with polycythemia vera. Methods: Data from 351 JAK2 V617F-positive patients diagnosed with PV were collected online from 15 haematology centres reporting clinical characteristics, therapeutic interventions, venous and arterial thromboembolic events, and myelofibrotic or leukaemic transformations. Vascular events (thromboembolic and haemorrhagic) were evaluated before and after diagnosis based upon the Landolfi risk assessment scale. Results: TE were reported on 116 occasions (106 patients) before diagnosis and 152 occasions (102 cases) during follow-up. Compared to before diagnosis, after diagnosis frequency of major arterial events decreased from 11.7% to 2.6% (p<0.0001), and minor venous events increased from 2.0% to 14.2% (p<0.0001); there was no significant change in number of major venous events (from 6.3% to 8.8%; p=0.25) or minor arterial events (from 13.1% to 17.7%; p=0.12). Bleeding events were recorded in 6.4% of patients. Despite treatment, 42.2% of patients with prior thromboembolic events had recurrent thromboembolic complications. After diagnosis age and prior history of thromboembolic events were independent risk factors for arterial events, and white blood cells and diabetes for venous events. Hydroxyurea use in the low+moderate risk Landolfi group slightly, but not significantly, increased thromboembolic event risk (p=0.74). Conclusions: This registry enables characterisation of patients with polycythemia vera. Data suggest the need for accuracy of diagnostic criteria and compliance with risk-adapted therapeutic guidelines.

Anagrelide reduces thrombotic risk in essential thrombocythaemia vs. hydroxyurea plus aspirin

To evaluate the reduction in thrombotic events (TE) in patients with essential thrombocythaemia (ET) treated with anagrelide versus hydroxyurea + aspirin (HU + ASA).

Az alacsony átlagos vörösvértest-hemoglobin alkalmas a vashiány szűrésére

Absztrakt Bevezetes: A vashiany szeles nepreteget erintő problema, szűrővizsgalata fontos egeszsegugyi kerdes. Celkitűzes: A szerzők arra a kerdesre kerestek valaszt, hogy a laboratoriumi automatak altal meghatarozott verkepparameterek kozul az alacsony MCH alkalmas-e a vashiany szűresere. Modszer: A Somogy Megyei Kaposi Mor Oktato Korhaz kozponti laboratoriumaban a 2013. januar 1. es 2015. junius 30. kozotti 30 honapos időszakban 247 705 verkepvizsgalat es 10 840 vasanyagcsere-vizsgalat tortent. A verkepvizsgalat alacsony atlagos vorosvertest-hemoglobinerteket hasonlitottak ossze az egyidejűleg elvegzett vashianyt igazolo parameterekkel. Eredmenyek: 830 betegben talaltak alacsony (28 pg alatti) atlagos vorosvertest-hemoglobinerteket es szimultan elvegzett vasanyagcsere laboratoriumi parametereket. Kozuluk 679 beteg eseteben (82%) az alacsony atlagos vorosvertest-hemoglobinertek vashiannyal jart egyutt. 126 hemodializalt (15%), 6 thalassaemias (minor), 8 myelofibrosisos, 5 rheumatoid arthritises beteg ese...

Philadelphia-negatív krónikus myeloproliferativ neoplasia regiszter magyarországi létrehozása

Absztrakt Bevezetes: A betegsegregiszterek kialakitasa es műkodese az epidemiologiai adatok gyűjtesen tul a korszerű betegellatas es a hosszu tavra is tervező egeszsegpolitikai dontesek meghozatalat segiti. Celkitűzes: A szerzők a magyarorszagi Philadelphia-negativ myeloproliferativ neoplasiaban szenvedő betegek es a betegseg hazai jellemzőinek osszegyűjteset tűztek ki celul. Modszer: A Tudomanyos es Kutatasetikai Bizottsag 2013. aprilis 8-an kelt engedelyenek birtokaban online elektronikus adatgyűjtes indult a magyarorszagi hematologiai ellatohelyeken. Az epidemiologiai adatok rogzitesen tul felmertek a betegsegek jellemzőit a diagnozis idejen (verkep- es csontvelőelteresek), valamint a kiserő cardiovascularis kockazati tenyezőket, amely alapjan kockazatstratifikacio is tortent. Vizsgaltak tovabba a hazai kezelesi szokasokat. Eredmenyek: 2015. junius 30-ig 901 beteg adatat rogzitettek 15 hazai centrumbol, tisztitas utan 858 beteg (426 polycythaemia veras, 350 essentialis thrombocythaemias es 82 myelofibr...INTRODUCTION The establishment and operation of disease registry can be used to collect data on epidemiology cases. In addition, the registry can help to work out medical and health economical and political decisions for longer term. AIM The aim of the authors was to collect and analyse data of patients with Philadelphia negative neoplasia in Hungary and draw conclusions about the basic types and features of the relevant disease. METHOD An online electronic data collection system has been established, based on the permission of the Regional and Institutional Committee of Science and Research Ethics obtained in April 8, 2013. Data collection has been initiated by hematology centres in Hungary. In addition to collection of the epidemiologic data, blood and bone marrow analysis data have been collected, as well. Also, based on cardiovascular factors, risk stratification has been established. Finally, the authors have investigated the method and practice of patient treatment in Hungary. RESULTS Data of 901 patients from 15 Hungarian haematology centres have been recorded up to the date of June 30, 2015. After clarification of the data, 426 polycythaemia vera, 350 essential thrombocythaemia and 82 myelofibrosis cases were used for analysis. CONCLUSIONS An online registry has been established which helps to clarify and analyse the basic features of certain medical cases and their treatment in Hungary. Including additional medical centres could help to improve the accuracy of medical analysis.

Low Mean Cell Haemoglobin is a Valuable Parameter of Thrombotic Risk Stratification in Patients with Polycythemia Vera

Objectives: Thrombosis is a leading cause of morbidity and mortality in patients with Philadelphia negative chronic myeloproliferative neoplasms (MPNs). There are many thrombosis risk stratifications used in this patient group taking into consideration the age, thrombosis history and cardiovascular factors (hypertension, hypercholesterinaemia, hyper-trigliceridaemia, thrombocytosis, smoking and diabetes mellitus). In this work we evaluated the possible role of iron deficiency in thrombotic events (TE) of the polycythaemia vera (PV) patients. Methods: We considered the low mean cell haemoglobin (MCH <28 pg) value as a parameter to assess the iron deficiency in the multicentre database (15 Hungarian haematology centres) of our HUMYPRON GROUP (Hungarian MPN Working Group). The MCH values, recorded at the time of diagnosis of 296 patients with polycythemia vera, were retrospectively analysed.Results: The low MCH, at the diagnosis, was found to be a risk factor for thrombotic events occurring after diagnosis (OR: 1.966). It was also shown as an additive and independent parameter in the Tefferi high-risk patient groups, and combining it with Tefferi risk stratification an extremely high thrombotic risk group could be determined (Nagelkerke R square: 0.084). We have supposed that low MCH in PV reveals a disease form featured with a high proliferation activity. Our hypothesis was confirmed with a sub-study (n=52) showing that the high JAK2V617F allele burden was significantly correlated with the low MCH (p=0.005) and the high white blood cell count (WBC) (p<0.001).Conclusions: Iron deficiency, existing at the time of diagnosis of PV, was proven to be a risk factor for imminent thrombotic events. The low MCH was found to be a strong additive factor when it was combined with the known thrombotic risk stratification systems. The low MCH showed significant correlation with the high JAK2V617F allele burden.

Philadelphia-negatív krónikus Myeloproliferativ Neoplasia Magyarországi Regiszter. Polycythaemia verás betegeink adatainak elemzése

Intruduction and aim: The Hungarian National Registry for Philadelphia chromosome negative myeloproliferative neoplasms has been developed. The aim of the recent study is to assess the clinical characteristics of Hungarian patients with polycythemia vera. METHOD Data of 351 JAK2V617F and exon 12 mutation positive polycythemia vera patients were collected online from 15 haematology centres reporting epidemiologic, clinical characteristics, diagnostic tools, therapeutic interventions, thromboembolic complications, disease transformations. Vascular events prior to and after diagnosis were evaluated upon the Landolfi risk assessment scale. RESULTS 116 thromboembolic events were reported in 106 PV patients prior to diagnosis and 152 occasions in 102 patients during follow-up. The frequency of major arterial events were significantly reduced (p<0.0001) and the minor venous events were significantly elevated (p<0.0001) after the diagnosis. Major hemorrhagic complications were found in 25 and transformation in 26 cases. CONCLUSIONS Our registry allows to collect and evaluate the features of patients with polycythemia vera. The Landolfi risk stratification was proven to be useful. Based on evaluated data, accuracy of diagnostic criteria and compliance to risk-adapted therapeutic guidelines are needed. Orv Hetil. 2017; 158(23): 901-909.Absztrakt: Bevezetes es celkitűzes: A HUMYPRON munkacsoport altal 2013-ban letrehozott Philadelphia-negativ myeloproliferativ neoplasias betegek magyar regisztereből a polycythaemia veras betegek adatait elemezzuk. Modszer: A 15 hematologiai centrumbol regisztralt 351 JAK2V617F- es exon-12-mutaciopozitiv polycythaemia veras beteg epidemiologiai, klinikai, diagnosztikus es kezelesi jellemzőit, vascularis es transzformacios esemenyeit dolgoztuk fel. A diagnozist megelőző es azt kovető thromboembolias esemenyeket a Landolfi szerinti rizikofelmeres alapjan ertelmeztuk. Eredmenyek: A diagnozist megelőzően 106 betegben 116, a diagnozist kovető időszakban 106 betegben 152 thromboembolias esemenyt regisztraltunk. A major arterias esemenyek szignifikansan csokkentek (p<0,0001), a minor venas esemenyek szignifikansan fokozodtak (p<0,0001) a diagnozist kovetően. A betegseg transzformaciojat 26 esetben, a major verzest 25 esetben eszleltuk. Kovetkeztetesek: Online regiszterunk konnyen kezelhető, lehetőve teszi a haza...

Philadelphia-negatív krónikus Myeloproliferativ Neoplasia Magyarországi Regiszter. Essentialis thrombocythaemiás betegeink adatainak elemzése

Absztrakt: Bevezetes: Myeloproliferativ neoplasia regisztert alkalmaztunk a magyarorszagi betegek adatainak gyűjtesere. Celkitűzes: A regisztralt essentialis thrombocythaemias betegek adatait kivantuk bemutatni. Modszer: A WHO 2008-as diagnosztikus kriteriumaira epulő online regisztert, a thrombosisriziko-becslesre a Landolfi-stratifikaciot alkalmaztuk. Eredmenyek: 15 magyar hematologiai centrum 2015. juniusig regisztralt 350 essentialis thrombocythaemias betegenek adatait elemezzuk. Az atlag kovetesi idő hat ev. Az epidemiologiai parameterek, a diagnozist megelőző es azt kovető thromboembolias esemenyek hasonlo eredmenyt mutattak az irodalombol mar ismertekkel. 139, anagreliddel es 141, hidroxiurea + aszpirin kezelt beteg adatait hasonlitottuk ossze. A major arterias es venas esemenyek tekinteteben nem talaltunk elterest a ket csoport kozott, de otodannyi minor esemenyt eszleltunk az anagrelidkezelteknel (p<0,001). A diagnozist kovető esemenyek csak a kezelessel es a diagnozist megelőző thromboticus esem...