The Possible Role of Pathogens and Chronic Immune Stimulation in the Development of Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. The disease is very heterogeneous, with distinct genetic alterations in subtypes. The WHO 2022 5th edition classification identifies several minor groups of large B-cell lymphoma where the pathogenetic role of viruses (like EBV and HHV-8) is identified. Still, most cases fall into the group of DLBCL not otherwise specified (NOS). No review focuses only on this specific lymphoma type in the literature. The pathogenesis of this entity is still not fully understood, but several viruses and bacteria may have a role in the development of the disease. The authors review critical pathogenetic events in the development of DLBCL (NOS) and summarize the data available on several pathogenetic viruses and bacteria that have a proven or may have a potential role in the development of this lymphoma type. The possible role of B-cell receptor signaling in the microenvironment is also discussed. The causative role of the Epstein-Barr virus (EBV), human herpesvirus-8 (HHV-8), Hepatitis C virus (HCV), human immunodeficiency virus (HIV), Hepatitis B virus (HBV), and other viruses are explored. Bacterial infections, such as Helicobacter pylori, Campylobacter jejuni, Chlamydia psittaci, Borrelia burgdorferi, and other bacteria, are also reviewed.

Transfusion-Transmitted Disorders 2023 with Special Attention to Bone Marrow Transplant Patients.

Transfusion medicine is traditionally a strong/fundamental part of clinical practice, saving hundreds of millions of lives. However, blood-borne or transmitted infections are a well-known and feared possibility, a risk we relentlessly mitigate. Pathogens are continuously and rather quickly changing, so during the last decade, many, sometimes exotic, new pathogens and diseases were recorded and analyzed, and some of them were proved to be transmitted with transfusions. Blood or blood component transfusions are carried out after cautious preparative screening and inactivation maneuvers, but in some instances, newly recognized agents might escape from standard screening and inactivation procedures. Here, we try to focus on some of these proven or potentially pathogenic transfusion-transmitted agents, especially in immunocompromised patients or bone marrow transplantation settings. These pathogens are sometimes new challenges for preparative procedures, and there is a need for more recent, occasionally advanced, screening and inactivation methods to recognize and eliminate the threat a new or well-known pathogen can pose. Pathogen transmission is probably even more critical in hemophiliacs or bone marrow transplant recipients, who receive plasma-derived factor preparations or blood component transfusions regularly and in large quantities, sometimes in severely immunosuppressed conditions. Moreover, it may not be emphasized enough that transfusions and plasma-derived product administrations are essential to medical care. Therefore, blood-borne transmission needs continued alertness and efforts to attain optimal benefits with minimized hazards.

Autologous Transplantation May Still Effectively Treat Relapsed Diffuse Large B-Cell Lymphoma in Selected Patients.

Treating relapsed and refractory diffuse large B-cell lymphoma is still challenging for clinicians, but the available CAR-T and bispecific antibodies have revolutionized therapy. Autologous stem cell transplantation was the most effective treatment modality previously. The authors reported data from a single center over ten years. The retrospective study included 116 patients, with 53 relapsed cases, 39 primary refractory cases, 19 who had CNS involvement, and 5 who had received primary consolidation transplants. The median duration of follow-up was 46 months. The median event-free survival was 75 months, and the median overall survival was 105 months for all cases. Five-year overall survival was 59%, and event-free survival was 54%. Pretreatment prognostic factors at diagnosis had no effect on the outcome of transplantation. The authors found no difference between survival in relapsed or refractory cases, and the number of salvage lines or the germinal center/activated B-cell type also did not influence the results. Complete metabolic response before transplantation confirmed by 18FDG PET/CT strongly affected survival. The pre-transplant creatinine and CRP levels significantly influenced the long-term outcome. The number of stem cells infused did not affect survival, but engraftment within nine days did result in a longer survival. These data support the finding that the response to salvage therapy did facilitate the identification of a better prognostic group who may still benefit from autologous transplantation.

A potentially new thromboembolic event scoring system 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 analyse the thromboembolic events (TE) of Hungarian patients with polycythemia vera (PV). METHODS: Data from 351 JAK2 V617F-positive patients diagnosed with PV were collected online from 15 haematology centres reporting clinical characteristics, therapeutic interventions and thromboembolic events. TE events were evaluated before and after diagnosis based upon the Landolfi and Tefferi risk assessment scales. RESULTS: TE were reported on 102 patients before diagnosis and 100 during the follow-up period. Comparing to the frequency of major arterial events before PV diagnosis, we can notice a decreasing tendency after diagnosis: from 12.3% to 2.6% (p < .00003). There was no significant change in the rate of major venous events (from 5.1% to 8.5%; p = .1134) or minor arterial events (from 11.7% to 17.4%; p = .073). Bleeding events were recorded in 5.7% of patients. Despite treatment with HU + ASA, 44 patients (43.1%) with prior TE had recurrent thromboembolic complications. The particular analysis of our data revealed a new TE scoring system based on: age, gender, previous TE and iron deficiency at the time of diagnosis. CONCLUSIONS: Our registry enables characterisation of patients with PV. The high level of recurrent TE events highlights the need for more effective and risk-adapted therapy.

Von Willebrand Factor and Platelet Levels before Conditioning Chemotherapy Indicate Bone Marrow Regeneration following Autologous Hematopoietic Stem Cell Transplantation.

Autologous hematopoietic stem cell transplantation (HSCT) is often complicated by hemostatic and thrombotic events associated with endothelial cell injury. Thrombotic complications are affected by a disturbed balance between platelets, circulating von Willebrand factor (VWF), and its specific protease, ADAMTS13. HSCT-associated endothelial dysfunction, impaired hemostasis, and inflammation are interrelated processes, and research on the complex interplay of conditioning regimens from engraftment to bone marrow regeneration remains intensive. This prospective observational study comparing lymphoma and multiple myeloma (MM) patients who underwent autologous HSCT explored how platelet count, VWF level, ADAMTS13 activity, and C-reactive protein (CRP) level as potential markers (1) vary in response to therapy, (2) differ between the 2 groups, and (3) correlate with the remission state at 100 days after HSCT. We correlated the quantitative changes in platelet count and levels of VWF, ADAMTS13, and CRP with one another during HSCT and in the remission state in 45 patients with lymphoma and 59 patients with MM who underwent autologous HSCT between 2010 and 2013 at the University of Debrecen. Samples were collected at the start of conditioning chemotherapy, on the day of stem cell transplantation, and at 5, 11, and 100 days following HSCT. CRP levels peaked when platelet counts dropped to a minimum, and these changes were much more pronounced in the lymphoma group. VWF level was the highest, with lower ADAMTS13 activity, at platelet engraftment in both patient groups equally. Diagnostic evidence indicative of thrombotic complications was not found. In the lymphoma group, VWF level prior to conditioning had statistically significant correlations with platelet count, CRP level, and hemoglobin concentration at the time of bone marrow regeneration (P < .001) and during the remission state (P = .034). In the MM group, platelet count before conditioning was correlated with platelet count (P < .001) and white blood cell count (P = .012) at the time of bone marrow regeneration. The statistically significant correlation of the markers at the time of bone marrow regeneration with the preconditioning VWF levels in lymphoma and with the preconditioning platelet counts in MM might indicate the clinical significance of the bone marrow niches of arterioles and megakaryocytes, respectively, where the stem cells are located and regulated. Because preconditioning VWF levels are associated with remission after HSCT in lymphoma patients, VWF should be screened before conditioning, along with the markers used in HSCT protocols, to optimize personalized treatment and reduce therapeutic risks.

Recent changes in paradigms in the management of adulthood chronic idiopathic thrombocytopenic purpura / Megújuló szemlélet és immunmodulációs törekvések a felnottkori idiopathiás immunthrombocytopenia terápiájában

The scenario of immune pathomechanism-based first- and second-line therapies of immune thrombocytopenia (i.e., immunosuppression, splenectomy) substantially changed approximately more than 20 years ago, giving place and important role for thrombopoietin analogs in steroid refractory cases, positioning splenectomy as third-line intervention. Although this approach became dominant and powerful, refractory cases urged the search for further medications. More recently, the traditional immunological approach received more attention again, and new targets were determined: (1) shortening selectively IgG life span and clearance, (2) modifying complement system in an effort to reduce antibody binding to platelet surface, (3) cell signaling pathway modification efforts to reduce antiplatelet phagocytic events, mainly spleen tyrosine kinase and Bruton tyrosine kinase inhibitory compounds. These new agents seem to be capable alone and probably in different combinations and sequence of increasing platelet count even in thrombopoietin analog refractory adult chronic thrombocytopenic purpura cases. These promising approaches probably will bring new treatment schedules in the adult chronic thrombocytopenic purpura field quite soon, and the scenario moves back to the refreshed immunological basis rewriting many elements of the therapeutic algorithm of thrombocytopenic purpura.

rs779805 Von Hippel-Lindau Gene Polymorphism Induced/Related Polycythemia Entity, Clinical Features, Cancer Association, and Familiar Characteristics.

Increased red blood cell count may result from primary erythrocytosis (polycythemia vera), but it is often due to secondary causes with increased erythropoietin levels. Secondary erythrocytosis may also be congenital due to different gene mutations of hemoglobin, hemoglobin stabilization proteins, EPO receptors, or oxygen sensing pathways. Von Hippel- Lindau gene mutation causes altered tissue oxygen sensation in VHL disease, usually with normal hemoglobin. Germline VHL mutations associate with classical VHL disease and represent genetic susceptibility for pheochromocytoma. VHL polymorphisms are mostly considered an innocent phenomenon. Still, some data indicate that these polymorphisms are not always harmless and can occur with prostate, renal, and colon cancer or even with isolated erythrocytosis. Seventy-eight patients referred to our department with elevated hemoglobin were screened for VHL mutations. There were no classical somatic VHL mutations. However, we found heterozygous (GA) or homozygous (AA) rs779805 VHL c.-195G>A polymorphism accompanied by erythrocytosis. These patients are Jak-2 negative, with normal or elevated EPO levels, sometimes with family accumulations and often phlebotomy needs, and in some cases with malignancies in the family. No other cause of erythrocytosis was found. We use phlebotomy regularly, and for those with cardiovascular risk factors, we recommend aspirin.

Maintenance therapy in malignant oncohematology, recent advances, evolving concepts / Fenntartó kezelési módok felnottkori rosszindulatú hematológiai betegségekben.

Maintenance therapy has been the strong and standard element of many acute lymphoblastic leukaemia protocols, used much less frequently and systematically in adult oncohematological disorders. The first adult maintenance efforts appeared in follicular and mantle cell lymphoma (mostly monoclonal antibody based), along with an early maintenance effort to prolong the plateau phase of myeloma. For the time being, after a long debate, the prognosis-dependent type of consolidation and maintenance became - sometimes until relapse - the standard approach in myeloma patients. The so-called small molecules, which turned out to be effective as induction and relapse agents, are continuously moving toward maintenance settings. Moreover, maintenance efforts seem to be more and more considered and used in transplanted or some non-transplanted acute myeloid leukaemia patients as well. Nevertheless, maintenance should be patient-friendly, easy to use (e.g., tablets) by enabling short outpatient office time, done not very frequently, and as much quality-of-life-based as possible. Orv Hetil. 2020; 161(38): 1623-1628.

Anagrelide influences thrombotic risk, and prolongs progression-free and overall survival in essential thrombocythaemia vs hydroxyurea plus aspirin.

OBJECTIVE: We report an extension study of patients with essential thrombocythaemia (ET) in the Hungarian Myeloproliferative Neoplasm (HUMYPRON) Registry, which demonstrated that over 6 years anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous thrombotic events (TEs) vs hydroxyurea+aspirin. METHODS: Data on patients with ET were collected through completion of a questionnaire developed according to 2008 WHO diagnostic criteria and with regard to Landolfi, Tefferi and IPSET criteria for thrombotic risk. Data were entered into the registry from 14 haematological centres. TEs, secondary malignancies, disease progression and survival were compared between patients with ET treated with anagrelide (n = 116) and with hydroxyurea+aspirin (n = 121). RESULTS: Patients were followed for (median) 10 years. A between-group difference in the number of patients with TEs was observed (25.9% anagrelide vs 38.0% hydroxyurea+aspirin; P = .052). Minor arterial events were more frequently reported in the hydroxyurea+aspirin group (P < .001); there were marginally more reports of major arterial events in the anagrelide group (P = .049). TE prior to diagnosis was found to significantly influence TE incidence (P > .001). Progression-free survival (P = .004) and survival (P = .001) were significantly increased for the anagrelide group vs hydroxyurea+aspirin. CONCLUSIONS: Anagrelide reduced TEs, and increased progression-free and overall survival vs hydroxyurea+aspirin over (median) 10 years.

Health-related quality of life in the phase III GALLIUM study of obinutuzumab- or rituximab-based chemotherapy in patients with previously untreated advanced follicular lymphoma.

Health-related quality of life was a secondary endpoint in the phase III GALLIUM study in previously untreated patients with follicular lymphoma who were treated with rituximab- or obinutuzumab-chemotherapy. Patients were randomized 1:1 to receive induction therapy with obinutuzumab- or rituximab-chemotherapy and maintenance in responders. Health-related quality of life was assessed using the Functional Assessment of Cancer Treatment-Lymphoma questionnaire, incorporating well-being and lymphoma-specific subscales. Assessments were performed at baseline, and during induction, maintenance, and follow-up (maximum 84 months). Clinically meaningful responses were defined by minimally important difference values. Of 1202 randomized patients (median follow-up 57.4 months), 557/601 (92.7%; obinutuzumab-chemotherapy) and 548/601 (91.2%; rituximab-chemotherapy) completed all Functional Assessment of Cancer Treatment-Lymphoma scales at baseline. Mean baseline health-related quality of life scores were similar between both arms, with all patients having some functional impairment and lymphoma symptoms. Over the course of treatment, mean health-related quality of life remained similar in both arms. Equal proportions of patients in both arms achieved minimally important difference by the Functional Assessment of Cancer Treatment-Lymphoma lymphoma-specific subscale and summary scales throughout induction, maintenance, and follow-up. On each summary scale, ~ 50% of patients in each arm achieved minimally important difference by maintenance month 2. In GALLIUM, similar improvements in health-related quality of life were seen with obinutuzumab- and rituximab-chemotherapy, suggesting that both treatments reduced lymphoma-related symptoms, and treatment-related side effects did not abrogate these improvements in well-being. ClinicalTrials.gov identifier: NCT01332968.

[A new era of transfusion-transmitted pathogens, infections. Renewed need for updating standards for clinicans along with blood banking]. / Új korszak és új szempontok a transzfúziós kórokozó-átvitel kockázatában, különös tekintettel a rendszeres plazmaeredetu készítményre szoruló haemophiliás betegekre.

Preparative and clinical transfusiology and transfusion, a majestic part of clinical medicine saved the life of hundred millions. However, bloodborne or transmitted infections became a serious issue in France in the 1980s, when many haemophiliacs were infected by HIV or hepatitis C virus by receiving plazma FactorVIII concentrates. This resulted in a quick and powerful development of screening as well as pathogen-inactivating methods, which reduced pathogen contamination and transmission to minimal levels. Times and pathogens are continously and rather quickly changing, so during the last decade many - not only egzotic - new pathogens and diseases were recognised, and some of them (e.g., Zyka virus, Ebola, hepatitis E virus, etc.) can also be transmitted by blood or blood-component transfusions, and in some instances they escape from standard screening and inactivation procedures. Hereby we try to focus and draw attention to some of these potentially pathogenic new bloodborne microbiological agents, and along with this we try to emphasize the significance of application of updated next generation screening and inactivation procedures. Interestingly a recent British trial, based on large population data, showed some evidence of a slight increase of non-Hodgkin lymphoma incidence in patients with multiple previous transfusions. Probably these facts are even more important in haemophiliacs, who receive prophylactic treatment 3 times weekly either by plasma factor concentrates derived from multiple donors or by gene synthetic factor sources. It is important that haemophiliac patient and family should receive the necessary information, and go for a fully informed consent based on the potential advantages and hazards of a particular treatment modality, the same way as in the chronic treatment of other diseases. Orv Hetil. 2018; 159(37): 1495-1500.

Impact of extramedullary disease in patients with newly diagnosed multiple myeloma undergoing autologous stem cell transplantation: a study from the Chronic Malignancies Working Party of the EBMT.

We investigated extramedullary disease in newly diagnosed multiple myeloma patients and its impact on outcome following first-line autologous stem cell transplantation. We identified 3744 adult myeloma patients who received up-front single (n=3391) or tandem transplantation (n=353) between 2005 and 2014 with available data on extramedullary involvement at diagnosis. The overall incidence of extramedullary disease was 18.2% (n=682) and increased per year from 6.5% (2005) to 23.7% (2014). Paraskeletal involvement was found in 543 (14.5%) and extramedullary organ involvement in 139 (3.7%). More patients with extramedullary organ involvement had multiple involved sites (≥2; P<0.001). In a comparison of patients with single sites with patients without the disease, up-front transplantation resulted in at least similar 3-year progression-free survival (paraskeletal: P=0.86, and extramedullary organ: P=0.88). In single paraskeletal involvement, this translated less clearly into worse 3-year overall survival (P=0.07) while single organ involvement was significantly worse (P=0.001). Multiple organ sites were associated with worse outcome (P<0.001 and P=0.01). First-line treatment with tandem compared with single transplantation resulted in similar survival in patients with extramedullary disease at diagnosis (P=0.13 for both).

[Treatment of relapsed Hodgkin lymphoma after autologous stem cell transplantation]. / Így kezeljük az autológ ossejt-transzplantáció után kiújult Hodgkin-lymphomát.

Approximately 10-30% of Hodgkin lymphoma patients relapses or experience refractory disease after first line treatment. Nowadays, autologous stem cell transplantation can successfully salvage half of these patients, median overall survival is only 2-2.5 years. Several prognostic factors determine success of autologous stem cell transplantation. Result of transplantation can be improved considering these factors and using consolidation treatment, if necessary. Patients who relapse after autologous transplantation had worse prognosis, treatment of this patient population is unmet clinical need. Several new treatment options became available in the recent years (brentuximab vedotin and immuncheckpoint inhibitors). These new treatment options offer more chance for cure in relapsed/refractory Hodgkin patients. Outcome of allogenic stem cell transplantation can be improved by using haploidentical donors. New therapeutic options will be discussed in this review. Orv Hetil. 2017; 158(34): 1338-1345.

[Hungarian Philadelphia negative chronic myeloproliferative neoplasia registry. Evaluation of the Polycythemia vera patients]. / 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.

[An audit of the Hungarian Philadelphia negative chronic myeloproliferative neoplasia registry. Evaluation of the essential thrombocythaemic patients]. / Philadelphia-negatív krónikus Myeloproliferativ Neoplasia Magyarországi Regiszter. Essentialis thrombocythaemiás betegeink adatainak elemzése.

INTRODUCTION: In order to establish and use a national registry, several Hungarian hematology centers collected data of myeloproliferative neoplasia patients. AIM: The recent publication is an analysis of the data of registered essential thrombocythaemic patients. METHOD: an online electronic registry has been established, using 2008 World Health Organization's diagnostic criteria and thrombotic risk was evaluated according to Landolfi stratification. RESULTS: Data of 350 essential thrombocythaemic patients from 15 Hungarian hematology centers entered up to the date of June 30, 2015 were used for analysis. Patients were followed up to (median) 6 years. The epidemiologic data (age, gender) and thrombotic events prior and after the diagnosis, were similar to the literature. The thrombotic events of anagrelide treated patient (n = 139) and the hydroxyurea + aspirin treated patients (n = 141) have been compared. The major arterial and venous events were similar between the groups, but there were fivefold less minor arterial and venous events in the anagrelide group (p<0.001). Thrombotic incidence after diagnosis were influenced only by medication and thrombotic events before the diagnosis. CONCLUSIONS: Anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous thrombosis, vs hydroxyurea + aspirin. Despite of the treatment the risk of thrombotic events after diagnosis remained high, and was significantly increased in patients with thrombosis before diagnosis. Orv. Hetil., 2017, 158(3), 111-116.

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

OBJECTIVE: To evaluate the reduction in thrombotic events (TE) in patients with essential thrombocythaemia (ET) treated with anagrelide versus hydroxyurea + aspirin (HU + ASA). METHODS: A questionnaire was developed using 2008 WHO diagnostic criteria, and thrombotic risk factors were stratified according to Landolfi criteria. Through questionnaire completion, clinicians at Hungarian haematological centres entered data into the Hungarian MPN Registry on patients with myeloproliferative neoplasms. Based on ET registry data, TEs in anagrelide-treated patients (n = 139) were compared with HU + ASA-treated patients (n = 141). RESULTS: Patients were followed up for (median) 6 yr. TEs were reported in significantly fewer anagrelide-treated patients versus HU + ASA (15.1% versus 49.6%; P < 0.001). Numbers of major arterial and major venous events were similar between the groups, although there were over fivefold more minor arterial and minor venous events in the HU + ASA group (P < 0.001). While median age at diagnosis was older and length of follow-up shorter in the HU + ASA group (P < 0.05), this did not influence TE incidence; medication and TE before diagnosis only influenced TE incidence. CONCLUSIONS: Anagrelide significantly decreased the number of patients experiencing minor arterial and minor venous TEs versus HU + ASA over 6 yr. Risk of TE after diagnosis was significantly increased if the patient had TE before diagnosis.

[Drug treatment of acute myelogenous leukaemia. Current options and future perspectives]. / Az akut myeloid leukaemia gyógyszeres kezelése. Jelenlegi lehetoségek, jövobeli kilátások.

Acute myelogenous leukemia is a heterogeneous disease. Recent molecular mutational analysis techniques have shed more light on different, genetically well characterised types of the disease. Treatment approach is uniform except for acute promyelocytic leukemia. Application of the "3 + 7" induction treatment has been the gold standard in the past 40 years. While the dose of cytarabine has not been changed, escalating daunorubicine dose in younger (<60 years) patients with good performance status to 90 mg/m(2) had a positive impact on overall survival. High dose chemotherapy is tolerated poorly in patients older than 60 years of age and, as treatment is not curative in the elderly, improvement of overall survival and quality of life remains the main goal of management in these patients. Low intensity treatment is beneficial and can provide additional advantage over supportive care. Innovative and targeted therapy approaches might give promise to better management of patients with acute myelogenous leukemia.

Alternative salvage regimens for relapsed/refractory classical Hodgkin's lymphoma.

OBJECTIVE AND IMPORTANCE: Hodgkin's lymphoma (HL) is a well-curable disease. The treatment usually includes combined multiagent conventional chemotherapy and radiotherapy. One-fifth of the patients need repeated treatments because of relapse or primary progressive disease. Those HL patients, who cannot be cured at least with salvage therapy (including autologous haemopoietic stem cell transplantation (auto-HSCT)), have really unfavourable prognosis. INTERVENTION: For this heavily pretreated subset of HL patients, novel but less toxic treatment strategies should be considered. Brentuximab-vedotin (BV) is a novel targeted treatment option, which was administered after the failure of two different regimens in patients, who were ineligible for auto-HSCT or after the failure of auto-HSCT. Moreover, there are favourable data with chemotherapeutical regimens supplemented with rituximab not only in relapsed but also in newly diagnosed classical HL patients. Bendamustine, an almost forgotten 50-year-old drug, lives its renaissance in the twenty-first century, which can be administered in refractory HL as well. Combination of the 'new' and 'old' drugs might be also helpful. CONCLUSION: Our data suggest that rituximab plus bendamustine (supplemented with or without BV) could be a suitable alternative bridging salvage therapy for heavily pretreated HL patients.

Phase III, randomized study of ofatumumab versus physicians' choice of therapy and standard versus extended-length ofatumumab in patients with bulky fludarabine-refractory chronic lymphocytic leukemia.

We report results of a randomized, phase III study of ofatumumab versus physicians' choice treatment in patients with bulky fludarabine-refractory chronic lymphocytic leukemia and explore extended versus standard-length ofatumumab treatment. Patients (79 ofatumumab, 43 physicians' choice) completed a median 6 (ofatumumab) or 3 (physicians' choice) months' therapy. Ofatumumab-treated patients with stable disease or better were randomized (2:1) to 6 months' extended ofatumumab treatment or observation. Although the study did not meet the primary endpoint of progression-free survival (PFS) by independent review committee (ofatumumab: 5.4 months, physicians' choice: 3.6 months; p = 0.27), median PFS by investigators was significantly longer for ofatumumab versus physicians' choice (7.0 versus 4.5 months; p = 0.003) as was time to next therapy (median 11.5 versus 6.5 months; p = 0.0004). PFS and time to next therapy were significantly longer with ofatumumab extended treatment than observation (p = 0.026 and p = 0.002, respectively; n = 37). The adverse-event profile of long-term ofatumumab administration showed no unexpected findings (Clinicaltrials.gov identifier: NCT01313689).

[Development of the registry for Philadelphia-negative chronic myeloproliferative neoplasia in Hungary]. / Philadelphia-negatív krónikus myeloproliferativ neoplasia regiszter magyarországi létrehozása.

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.