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Despite the availability of many novel therapies for multiple myeloma, it remains an incurable disease with relapse fated in almost all patients. In the era of modern agents, second autologous stem cell transplantation still holds its role in patients relapsing after first-line autologous transplant. The authors reviewed a single-center experience with a second auto-SCT for relapsed multiple myeloma. Thirty patients had received a salvage auto-SCT at the institution. The median follow-up after diagnosis was 86 months, and the median time between transplants was 59.1 months. Response before second ASCT was the following: CR - 11 cases, VGPR - 9 cases, PR - 10 cases. Most patients received reduced dose (140 mg/m2) of melphalan as a conditioning regimen for the second auto-SCT. Treatment-related mortality was 3%. With a median follow-up time of 34 months after the second transplant, median progression-free survival was 24 months. The median PFS in the patients achieving CR or VGPR at day 100 after the second transplantation was 32 months. By 15 months, all patients achieved only partial remission progressed, with a median PFS of 8.5 months. During the follow-up period, no MDS or AML developed, and the frequency of second malignancy was also low, 3%. In conclusion, second autologous stem cell transplantation is a well-tolerated and effective treatment option for relapsed multiple myeloma in selected patients, though with a shorter PFS than in first remission.
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Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Terapia Recuperativa , Trasplante Autólogo , Humanos , Mieloma Múltiple/terapia , Mieloma Múltiple/patología , Masculino , Femenino , Persona de Mediana Edad , Terapia Recuperativa/métodos , Anciano , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Estudios de Seguimiento , Estudios Retrospectivos , Acondicionamiento Pretrasplante/métodos , Recurrencia Local de Neoplasia/patología , Tasa de SupervivenciaRESUMEN
Signaling pathways of Retinoblastoma (Rb) protein, Akt-kinase, and Erk-kinase (extracellular signal-regulated kinase) have an important role in the pathogenesis of acute myeloid leukemia. Constitutive activation of these proteins by phosphorylation contributes to cell survival by regulation of cell cycle, proliferation and proapoptotic signaling processes. According to previous data phosphorylated forms of these proteins represent a worse outcome for cancer patients. We investigated the presence of phosphorylated Rb (P-Rb), Akt (P-Akt) and Erk (P-Erk) proteins by Western blot technique using phospho-specific antibodies in bone marrow or peripheral blood samples of 69 AML patients, 36 patients with myelodysplastic syndrome (MDS) and 10 healthy volunteers. Expression level of PTEN (Phosphatase and tensin homolog) and PHLPP (PH domain and leucine-rich repeat Protein Phosphatase) phosphatases, the negative regulators of Akt kinase pathway were also examined. We tested the effect of these proteins on survival and on the correlation with known prognostic features in AML. We found 46.3% of AML patients had detectable P-Rb, 34.7% had P-Akt and 28.9% had P-Erk protein. 66.1% of patients expressing PTEN, 38.9% PHLPP, 37.2% both PTEN and PHLPP and 32.2% neither PTEN nor PHLPP phosphatases. Compared to nucleophosmin mutation (NPMc) negative samples P-Erk was significantly less in nucleophosmin mutated patients, P-Rb was significantly less in patients' group with more than 30 G/L peripheral leukocyte count by diagnosis. PHLPP was significantly present in FAB type M5. The expression of P-Rb represented significant better overall survival (OS), while P-Akt represented significantly worse event-free survival (EFS) in unfavorable cytogenetics patients. The presence of both PHLPP and PTEN phosphatases contributes to better OS and EFS, although the differences were not statistically significant. We confirmed significant positive correlation between P-Akt and PHLPP. Assessing the phosphorylation of Rb, Akt and Erk may define a subgroup of AML patients who would benefit especially from new targeted treatment options complemented the standard chemotherapy, and it may contribute to monitoring remission, relapse or progression of AML.
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Leucemia Mieloide Aguda , Nucleofosmina , Fosfohidrolasa PTEN , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patología , Pronóstico , Femenino , Masculino , Fosforilación , Persona de Mediana Edad , Anciano , Adulto , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Biomarcadores de Tumor/metabolismo , Anciano de 80 o más Años , Fosfoproteínas Fosfatasas/metabolismo , Fosfoproteínas Fosfatasas/genética , Adulto Joven , Tasa de Supervivencia , Síndromes Mielodisplásicos/metabolismo , Síndromes Mielodisplásicos/patología , Adolescente , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas NuclearesRESUMEN
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.
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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.
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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.
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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.
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Trastornos Mieloproliferativos , Policitemia Vera , Tromboembolia , Humanos , Policitemia Vera/complicaciones , Policitemia Vera/diagnóstico , Policitemia Vera/epidemiología , Hungría/epidemiología , Trastornos Mieloproliferativos/complicaciones , Trastornos Mieloproliferativos/diagnóstico , Trastornos Mieloproliferativos/epidemiología , Tromboembolia/diagnóstico , Tromboembolia/epidemiología , Tromboembolia/etiología , Hemorragia , Janus Quinasa 2/genéticaRESUMEN
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.
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Púrpura Trombocitopénica Idiopática , Trombopoyetina , Adulto , Agammaglobulinemia Tirosina Quinasa , Humanos , Inmunoglobulina G , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Quinasa Syk , Trombopoyetina/uso terapéuticoRESUMEN
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.
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Trasplante de Células Madre Hematopoyéticas , Trombosis , Humanos , Factor de von Willebrand/metabolismo , Médula Ósea/metabolismo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante Autólogo , Acondicionamiento Pretrasplante/métodos , Trombosis/patología , BiomarcadoresRESUMEN
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.
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Predisposición Genética a la Enfermedad/genética , Policitemia/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Adolescente , Adulto , Anciano , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
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.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Mieloma Múltiple/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adulto , Humanos , Leucemia Mieloide Aguda/patología , Mieloma Múltiple/patología , Recurrencia Local de Neoplasia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
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.
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Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/mortalidad , Trombosis/etiología , Trombosis/mortalidad , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Quimioterapia Combinada , Encuestas de Atención de la Salud , Humanos , Hungría , Hidroxiurea/administración & dosificación , Hidroxiurea/uso terapéutico , Quinazolinas/administración & dosificación , Quinazolinas/uso terapéutico , Sistema de Registros , Trombocitemia Esencial/epidemiología , Trombosis/epidemiología , Trombosis/prevención & control , Resultado del TratamientoRESUMEN
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.
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Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos Inmunológicos/administración & dosificación , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/psicología , Calidad de Vida/psicología , Rituximab/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Linfoma Folicular/diagnóstico , MasculinoRESUMEN
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.
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Plaquetas/microbiología , Transmisión de Enfermedad Infecciosa/prevención & control , Hemorragia/terapia , Transfusión de Plaquetas/métodos , Humanos , Transfusión de Plaquetas/efectos adversosRESUMEN
BACKGROUND: There is an unstable balance between pro- and anti-haemostatic processes in patients with cirrhosis. We hypothesized, that in patients with acute decompensation (AD) the major alterations of von Willebrand factor (VWF) could contribute to the pro-thrombotic situation as compared to patients with stable (ST) cirrhosis. PATIENTS AND METHODS: We analysed different parameters of VWF, including detailed multimer distribution by densitometry and platelet adhesion, together with adisintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) activity and antigen and C-reactive protein (CRP) levels in patients with ST cirrhosis (n = 99), with AD (n = 54) and controls (n = 92). RESULTS: VWF antigen, ristocetin co-factor as well as collagen-binding activities were elevated in both cirrhotic groups in a stepwise manner. There was a decrease in high and an increase in low molecular weight multimer ratios in the majority of ST cirrhosis. However, in 24 out of 54 AD patients, ultra-large VWF multimers (ultra-large molecular weight multimers [ULMWM]) were found. ADAMTS13 activity in ST and AD patients without ULMWM was similar to controls (median [interquartile range; IQR]%: 98 [67-132] and 91 [60-110] vs. 106 [88-117], respectively). The presence of ULMWM in AD patients was associated with low ADAMTS13 activity [33 (24-49)%] and high CRP level [23 (7.1-83.6) mg/L]. Adhesion of normal platelets showed a stepwise increase in the presence of cirrhotic plasmas, reaching the highest level in AD patients with ULMWM. CONCLUSION: Characteristic changes of VWF parameters are seen in ST cirrhosis. In AD patients, highly increased VWF and reduced ADAMTS13 activity could be found, along with the presence of ULMWM, which are possible markers and contributors of the disease progression.
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Coagulación Sanguínea , Cirrosis Hepática/sangre , Fallo Hepático Agudo/sangre , Trombosis/sangre , Factor de von Willebrand/metabolismo , Proteína ADAMTS13/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Mediadores de Inflamación/sangre , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/etiología , Masculino , Persona de Mediana Edad , Peso Molecular , Trombosis/diagnóstico , Trombosis/etiología , Adulto JovenRESUMEN
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).
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Trasplante de Células Madre Hematopoyéticas/mortalidad , Mieloma Múltiple/patología , Músculo Esquelético/fisiopatología , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/terapia , Recurrencia Local de Neoplasia/terapia , Pronóstico , Tasa de Supervivencia , Trasplante AutólogoRESUMEN
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.
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Antineoplásicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Inmunoconjugados/uso terapéutico , Brentuximab Vedotina , Quimioterapia de Consolidación/métodos , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/inmunología , Humanos , Inducción de Remisión , Terapia Recuperativa/métodos , Análisis de Supervivencia , Trasplante AutólogoRESUMEN
The author provides an overview of the use of recombinant activated FVII (rFVIIa, Novoseven), which is used over 30 years, based upon international publications and also on some modest own experience. Standard, approved indications (inhibitory cases, Glanzmann thrombasthenia, prophylaxis experience) are in the focus of this paper, emphasizing the specially rapid and efficacious way of Novoseven therapy, drawing attention to excellent safety issues regarding very low immunogenicity along with low number of thrombogenic complications. A careful, cautious and critical evaluation of Novoseven therapy is also provided in rather special forms of critical bleeding conditions considering international recommendations and institutional registry data. Orv Hetil. 2017; 158(24): 923-928.
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Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Coagulantes/uso terapéutico , Factor VIIa/uso terapéutico , Humanos , Proteínas Recombinantes/uso terapéutico , Trombastenia/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Policitemia Vera/epidemiología , Mielofibrosis Primaria/epidemiología , Sistema de Registros , Distribución por Edad , Anciano , Femenino , Humanos , Hungría , Masculino , Persona de Mediana Edad , Cromosoma Filadelfia , Medición de Riesgo , Factores de Riesgo , Distribución por SexoRESUMEN
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.
Asunto(s)
Trastornos Mieloproliferativos/tratamiento farmacológico , Trastornos Mieloproliferativos/epidemiología , Cromosoma Filadelfia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Quinazolinas/uso terapéutico , Sistema de Registros , Femenino , Humanos , Hungría , MasculinoRESUMEN
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.