Visszatérő szomatikus mutáció hajas sejtes leukémiában

A hajas sejtes leukémia olyan érett B-sejtes non-Hodgkin-lymphoma, amelyet egyedi klinikai, morfológiai és immunfenotípusbeli sajátosságok jellemeznek. A betegséget splenomegalia, progresszív pancytopenia és relatív indolens lefolyás kíséri. A diagnózis megszületése után a klinikai stádiumtól függ, hogy a „watchful waiting” stratégiát választjuk, avagy azonnali kezelés szükséges. Az első vonalban javasolt purin-nukleozid analógokkal (cladribin, pentostatin) akár több évtizedig tartó komplett remisszió is elérhető. A hajas sejtes leukémia néha igen komoly differenciáldiagnosztikai kérdéseket felvető betegség. A pontos diagnózis igen nagy horderejű, hiszen a rokon kórképek prognózisa és kezelése nagymértékben különbözik a hajas sejtes leukémiáétól. Ezért volt kiemelkedő fontosságú az a felismerés, hogy létezik olyan genetikai elváltozás, amely e betegségek elkülönítő diagnózisában döntő értékű. A BRAF gén V600E szomatikus mutációja hajas sejtes leukémiában szenvedő betegek csontvelői mintáiból izolált DNS-ben minden esetben jelen van, míg a rokon kórképekre ezen mutáció hiánya a jellemző. A szerzők a mutáció felismerésének és a mutációvizsgálat alkalmazásának jelentőségét foglalják össze. Orv. Hetil., 2013, 154, 123–127. | Hairy cell leukemia is a mature B-cell non-Hogkin lymphoma characterized by unique clinical, morphological and immunhistochemical features. Patients with hairy cell leukemia usually present with splenomegaly, progressive pancytopenia and a relative indolent clinical course. The diagnosis does not always indicate immediate treatment, as treatment depends on the clinical stage of the leukemia. Asymptomatic disease without progression requires a watchful waiting policy, while other categories usually need treatment. The treatment of choice is purin nucleosid analogues (pentostatin, cladribine) which can achieve complete remission even for decades. Interferon and monoclonal CD20 antibodies can also significantly prolong tevent free survival. Unfortunately, only the latter two therapies are easily available in Hungary. Splenectomy, which was suggested as first line treatment before the era of purin nucleosid analogues, is only recommended as ultimum refugium. Although hairy cell leukemia is a well-defined lymphoproliferative disease, sometimes it is difficult to differentiate it from other similar entities such as hairy cell leukema variant, splenic marginal zone lymphoma, small lymphocytic lymphoma etc. Making the correct diagnosis is of utmost importance because of the great difference in treatment modalities. Recently, a somatic mutation was found in all analysed hairy cell leukemia samples, but not in other splenic B-cell lymphomas. This article reviews the significance of this observation and presents the different types of methods for the detection of this mutation. Orv. Hetil., 2013, 154, 123–127

The connection between extracurricular, leisure time activities, religiosity and the reasons for drop-out

The interruption of tertiary education and the reduction in the dropout rate have been a central issue in educational sociology and education research. Exploring the possible reasons for dropping out can significantly contribute to reducing the trend. Our aim is to map the links between students dropping out and individual factors. Consequently, we investigate the connection between extracurricular and leisure-time activities, health behaviour and religiosity in relation to dropout. This is explained by the fact that one of the axioms of the literature on dropout is that belonging to civil networks usually strengthens the commitment to the successful completion of studies. In our analysis, we used the database created during the research carried out in 2018 by the Center for Higher Education Research and Development (CHERD-H) in the framework of project No. 123847 of the National Research, Development and Innovation Fund of Hungary, entitled The Role of Social and Organisational Factors in Student Dropout (DEPART 2018, N=605). Our results show that the neglect of study obligations among those who are disappointed in the course and further education is closely related to the shift in value preferences and an increase in the time spent with entertainment activities and partying. It can also be stated that students take part indifferent types of extracurricular activities only to a limited extent, and the different forms of participation in activities and religiosity are not related to the causes of dropout

A Comprehensive Immunophenotypic Marker Analysis of Hairy Cell Leukemia in Paraffin-Embedded Bone Marrow Trephine Biopsies-A Tissue Microarray Study

Hairy cell leukemia (HCL) is an uncommon B cell lymphoproliferation characterized by a unique immunophenotype. Due to low number of circulating neoplastic cells and 'dry tap' aspiration, the diagnosis is often based on BM trephine biopsy. We have performed a consecutive immunohistochemical analysis to evaluate diagnostic usefulness of various HCL markers (CD11c, CD25, CD68, CD103, CD123, CD200, annexin A1, cyclin D1, DBA.44, HBME-1, phospho-ERK1/2, TRAP, and T-bet) currently available against fixation resistant epitopes. We analyzed tissue microarrays consisting of samples gained from 73 small B-cell lymphoma cases, including hairy cell leukemia (HCL) (n = 32), HCL variant (HCL-v) (n = 4), B-cell chronic lymphocytic leukemia (B-CLL) (n = 11), lymphoplasmacytic lymphoma (LPL) (n = 3), mantle cell lymphoma (MCL) (n = 10), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n = 2), splenic B cell marginal zone lymphoma (SMZL) (n = 8), and splenic B cell lymphoma/leukemia, unclassifiable (SBCL) (n = 3) cases. The HCL cases were 100 % positive for all but 2 (DBA.44 and CD123) of these markers. Annexin A1 showed 100 % specificity and accuracy, which was followed by CD123, pERK, CD103, HBME-1, CD11c, CD25, CD68, cyclin D1, CD200, T-bet, DBA.44, and TRAP, in decreasing order. In conclusion, our results reassured the high specificity of annexin A1 and pERK, as well as the diagnostic value of standard HCL markers of CD11c, CD25, CD103, and CD123 also in paraffin-embedded BM samples. Additional markers, including HBME-1, cyclin D1, CD200, and T-bet also represent valuable tools in the differential diagnosis of HCL and its mimics

Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous surface and can be useful in the diagnosis of hairy cell leukemia and other indolent lymphoproliferations of villous B lymphocytes

The Hector Battifora mesothelial epitope-1 (HBME-1) monoclonal antibody has been generated against human mesothelioma cells and recognizes a biochemically unknown membrane epitope. We have accidentally found that the HBME-1 reacts with scattered lymphocytes showing villous surface in hyperplastic lymphoid tissue. To evaluate its reactivity pattern, we have performed a consecutive immunohistochemical study in nonneoplastic bone marrow and lymphoid samples (n = 40), as well as in malignant lymphoproliferations (n = 427), including hairy cell leukemia (HCL) (n = 72), HCL variant (HCL-v) (n = 13), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n = 8), splenic B cell marginal zone lymphoma (SMZL) (n = 59), and splenic B cell lymphoma/leukemia, not further classifiable on bone marrow morphology (SBCL) (n = 37) cases. The staining pattern of HBME-1 was compared to DBA.44. HBME-1+ villous lymphocytes were constantly detected in low number in nonneoplastic lymphoid tissues. With multicolor immunofluorescence staining, HBME-1+ lymphocytes showed a CD20+/CD79a+/IgM+ B cell phenotype. In B cell lymphoproliferations of villous lymphocytes, HBME-1 reactivity was demonstrated in 96 % of HCL, 39 % of HCL-v, 50 % of SDRPL, 12 % of SMZL, and 19 % of SBCL cases. Nodal and extranodal marginal zone lymphoma cases were positive in 12 % of the cases. A small minority (4 %) of the other B cell lymphomas and no T cell lymphoma revealed tumor cell reactivity with HBME-1. In conclusion, our study has established that HBME-1 reacts with a minor subset of B lymphocytes and a small proportion of B cell lymphomas, which has not been described previously. We suggest that HBME-1 can be a useful marker in the diagnosis of HCL and other indolent lymphoproliferations of villous B lymphocytes

Tapasztalatok az ipar 4.0-val – egy esetalapú elemzés

Mostanában számtalan tanácsadói anyag és szakcikk jelenik meg az ipar 4.0-ról és gazdaságra, illetve társadalomra gyakorolt hatásairól. Közös pontja ezen anyagoknak, hogy részletekbe menő gyakorlati példákat ritkán írnak le. A cikk célja, hogy egy cégnél nyújtson átfogó képet az ipar 4.0 adaptálásának kezdeti lépéseiről egy idehaza működő multinacionális vállalat példáján. A szerzők a vállalat által tett erőfeszítéseket az ipar 4.0 technológiákat rendező keretbe helyezik, számba veszik a kihívásokat és nehézségeket, a tapasztalt előnyöket és hátrányokat. Eredményeik alapján az ipar 4.0 teljes alkalmazása már a kezdeti szakaszban is jelentős eszközberuházásokat követel meg és komoly elvárásokat támaszt a munkaerő irányába is. Az irodalomban hangsúlyozott jelentős pozitív hatásokhoz (pl. profit, minőség, rugalmasság) képest az ipar 4.0 egyelőre olyan gazdag multinacionális vállalatok „drága játékszerének” tűnik, amelyeknek van idejük és erőforrásuk a kísérletezgetésre, elfogadva a nem megtérülés kockázatát is

Adjunctive Volasertib in Patients With Acute Myeloid Leukemia not Eligible for Standard Induction Therapy: A Randomized, Phase 3 Trial

Terapia de inducción estándar; Volasertib adyuvante; Leucemia mieloide agudaStandard Induction Therapy; Adjunctive Volasertib; Acute Myeloid LeukemiaTeràpia d'inducció estàndard; Volasertib adjuvant; Leucèmia mieloide agudaIn this phase 3 trial, older patients with acute myeloid leukemia ineligible for intensive chemotherapy were randomized 2:1 to receive the polo-like kinase inhibitor, volasertib (V; 350 mg intravenous on days 1 and 15 in 4-wk cycles), combined with low-dose cytarabine (LDAC; 20 mg subcutaneous, twice daily, days 1–10; n = 444), or LDAC plus placebo (P; n = 222). Primary endpoint was objective response rate (ORR); key secondary endpoint was overall survival (OS). Primary ORR analysis at recruitment completion included patients randomized ≥5 months beforehand; ORR was 25.2% for V+LDAC and 16.8% for P+LDAC (n = 371; odds ratio 1.66 [95% confidence interval (CI), 0.95–2.89]; P = 0.071). At final analysis (≥574 OS events), median OS was 5.6 months for V+LDAC and 6.5 months for P+LDAC (n = 666; hazard ratio 0.97 [95% CI, 0.8–1.2]; P = 0.757). The most common adverse events (AEs) were infections/infestations (grouped term; V+LDAC, 81.3%; P+LDAC, 63.5%) and febrile neutropenia (V+LDAC, 60.4%; P+LDAC, 29.3%). Fatal AEs occurred in 31.2% with V+LDAC versus 18.0% with P+LDAC, most commonly infections/infestations (V+LDAC, 17.1%; P+LDAC, 6.3%). Lack of OS benefit with V+LDAC versus P+LDAC may reflect increased early mortality with V+LDAC from myelosuppression and infections.This study was funded by Boehringer Ingelheim