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Introduction: Treatment of chronic lymphocytic leukaemia (CLL) continues to develop dramatically. Chemoimmunotherapy that historically represented the golden standard of treatment has been largely replaced by molecular-targeted therapies that are more effective and safer. Objective: A retrospective study to evaluate the efficacy and safety of innovative „chemo-free" therapy (ibrutinib and venetoclax) in patients with CLL. Material and methods: from January 2016 to September 2021, 83 patients with chronic lymphocytic leukaemia treated in our institute were included in the study. A total of 63 patients received ibrutinib (15.9% in front-line setting) and 20 patients received venetoclax +/– rituximab (85% as monotherapy and 5% in front-line setting). The median age was 64 years (range 39–81 years). Each group had a median of two prior lines of therapy (range 1–6). The median follow-up was 31 months for ibrutinib and 23 months for venetoclax. Results: the majority of patients responded to treatment with an overall response rate (ORR) of 92% for ibrutinib and 90% for venetoclax. The rate of complete remission was higher with venetoclax (relative risk – RR = 2.02, 95% CI: 1.16–3.5; P = 0.012). The 3-year progression-free survival (PFS) and overall survival (OS) were 82% and 83% for ibrutinib, 80% and 80% for venetoclax respectively. The majority of side effects reported were relatively mild to moderate. Conclusion: In our study, we demonstrate that novel agents, ibrutinib and venetoclax provide comparable results in patients with CLL treated outside clinical trials. [ABSTRACT FROM AUTHOR]

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Background: Haematopoietic stem cell transplantation (SCT) from HLA-identical sibling/family donors following myeloablative or non-myeloablative chemotherapy is a curative therapeutic method for younger patients with serious haematological disorders. Introduction of allogeneic SCT in our clinic has offered its availability for patients in our country. Due to our centre monopol position in alloSCT in Slovakia, reporting and comparing our results with international data is very important. Patients and methods: Between July 1989 and March 2001. 123 patients with haematological disorders aged 15-59 years (median 35 years) have undergone 133 SCTs from HLA-identical siblings. Their retrospective analysis is reported. The majority of patients (65 pts) suffered from chronic myelogenous leukemia (59 chronic phase, 2 accelerated and 4 blastic phase) or acute leukaemia (37 pts): 29 AML (16 in CR1 and 13 > CR1); 8 ALL (6 in CR1 and 2 > CR1), 12 severe aplastic anaemia, 6 myelodysplastic syndrome, 2 patients non-Hodgkin lymphoma and one myelofibrosis. The conditioning regimen for malignancies consisted of BUCY2, in advanced disease E-BUCY2, for SAA cyclophosphamide ± ATG. Source of stem cells was 101 times bone marrow and 32 times peripheral blood after G-CSF administration for 4 days. GVHD prophylaxis with CsA and short course of MTX was given. Results: As of March 18, 2001, 72 (59%) of 123 patients are alive 1-133 months, median time of observation 52 months. 51 (41%) of 123 patients died 1-30 months from SCT, median 3 months. 10 patients of 123 undervent second SCT (9 times with peripheral stem cells and one with bone marrow): 5 (50%) of 10 patients are alive, median 29 months (6-54 months) from second SCT and median 60 months (29-90 months) from thier first SCT. 5 (50%) patients died after second SCT median 1 months (1-17 months). Engraftment was in 129 SCTs but at 4 SCTs patients died (on day 10 to 21) too early to evaluate engraftment. Median time to reach ANC > 0,5 G/l was 18 days (10-31) after SCT, > 1,0 G/l 22 days (1240), median time to platelet count > 25 G/l 19 days (12 to >140 days) and to platelet count > 100 G/l 31 days (19 to >140 days). 100 day mortality is different in standard versus height risk patients with adveanced disease. 16% and 29% respectively. Acute GVHD occurred in 38% patients (grade I 9%, II 8%, III 17% and IV 4%), chronic GVHD in 29% patients at risk. Conclusions: Our data confirm, that allogeneic BMT from HLA-siblings after appropriate conditioning regimen is an effective treatment modality with acceptable risk for younger patients with serious haematological disorders. Second SCT is associated with higher risk of peritransplant mortality in our hands. [ABSTRACT FROM AUTHOR]

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care. 1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Omalizumab was proven to be effective and safe in patients with moderate-to-severe allergic asthma. However, there is no direct evidence of the benefits of add-on omalizumab in real-life practice in the Slovakian population., Aim: This subgroup analysis assessed the real-life effectiveness and safety of omalizumab in Slovakian patients with severe allergic asthma enrolled in the eXpeRience registry., Material and Methods: Patients who commenced omalizumab 15 weeks prior to inclusion were assessed for the physicians' global evaluation of treatment effectiveness (GETE), exacerbation rate, asthma symptoms, lung function, oral corticosteroid (OCS) use, rescue medication, hospitalizations, and school/work absenteeism at 16 weeks and 12 and 24 months., Results: Of 204 patients, 159 (77.9%) completed 2-year follow-up. As per GETE, 69.5% of patients treated with omalizumab achieved excellent/good response at 16 (±1) weeks. The proportion of patients with no severe clinically significant asthma exacerbations increased from 17.3% at pre-treatment to 82.4% and 92.0% at months 12 and 24, respectively. Maintenance OCS use was reduced to 17.0% and 15.3% of patients at 12 and 24 months, respectively, compared with 34.7% at baseline (BL). From BL until month 24, asthma control test scores improved from 11.6 to 20.3; rescue medication use/week decreased from 5.5 to 1.6 days; mean total number of days of asthma-related medical healthcare use decreased from 7.7 to 0.3 days and missed workdays decreased from 16.8 to 0.3 days. No new safety signals were observed., Conclusions: Add-on omalizumab was effective and well-tolerated in Slovakian patients, complementing the results observed in the overall population of eXpeRience., Competing Interests: This study was funded by Novartis Pharma AG, Basel, Switzerland. S.S. and L.D.T. are employees of Novartis Slovakia s.r.o. Bratislava, Slovakia. M.J. reports other support including honoraria, consultancy and speaker fees from Novartis, ALK, Stallergenes-Greer, MSD, Sanofi-Genzyme, Sanofi-Pasteur, Angelini, GSK, Novartis, Nutricia, Nestle, Mundipharma, Berlin-Chemie, CSL Behring, and Takeda, outside the submitted work., (Copyright: © 2023 Termedia Sp. z o. o.)

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for numerous malignant and nonmalignant diseases. The number of survivors and length of follow-up after successful HSCT is continually increasing. HSCT can induce damage of various organs and tissues - from minimal potentially progressive subclinical changes to life-threatening conditions. The aim of this thesis was to assess the prognostic value of high sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing and early identification of patients at high risk of a cardiac event after allogeneic HSCT., Patients and Methods: Sixty-three patients with the median age of 37 years at the time of allogeneic HSCT for hematologic diseases were studied. Cardiac bio-markers were serially measured before conditioning regimen and at days 1, 14 and 30 after HSCT. Cardiac systolic and diastolic functions were assessed before the conditioning regimen and 1 month after HSCT by echocardiography., Results: The differences in plasma NT-proBNP and hs-cTnT concentrations during the 30 days following HSCT were statistically significant (P < 0.001 vs. P = 0.02). Seven of 63 patients (11.1 %) developed a cardiac event defined as cardiovascular dys-rhythmias, pericarditis with cardiac tamponade and heart failure. By multivariate analysis, the strongest prognostic factor of cardiac event was an increased level of hs-cTnT and NT-proBNP persisted for a period of 14 days after HSCT (P < 0.0001). The area under the curve from hs-cTnT testing plus NT-proBNP testing together (AUC = 0.95) was superior to each dia-gnostic modality alone., Conclusion: Measurements of plasma NT-proBNP and hs-cTnT concentrations might be a useful tool for identification of high-risk patients requiring further cardiological follow up. Measurement of hs-cTnT plus NT-proBNP together was superior to hs-cTnT and NT-proBNP measurements alone.

Aim: Clinical outcomes of women who become pregnant during/after facilitated subcutaneous immunoglobulin (fSCIG) treatment are not well characterized. Materials & methods: This noninterventional, prospective, open-label, post authorization, pregnancy registry study assessed safety outcomes in mothers with primary immunodeficiency diseases who had ever received fSCIG before/during pregnancy and their infants (n = 7). Enrolled women received alternative treatment (arm 1: n = 2) or continued fSCIG (arm 2: n = 7) during pregnancy. Results: No treatment-related adverse events (AEs)/serious AEs (SAEs) were reported. 13 AEs occurred in mothers, including two SAEs (thrombocytopenia, pre-eclampsia; arm 2). A total of 17 AEs occurred in infants, including two SAEs (cleft lip, talipes calcaneovalgus; arm 2) with normal growth/development. Conclusion: Findings provide limited but useful safety data regarding women who received fSCIG before/during pregnancy and the growth/development of their infants. Clinical Trial registration: NCT02556775 (ClinicalTrials.gov); EUPAS5798.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) offers potentially curative therapy for numerous malignant and non-malignant diseases. The number of survivors and length of follow-up after successful HSCT is continually increasing. Hematopoietic stem cell transplantation can induce damage of various organs and tissues - from minimal potentially progressive subclinical changes to life-threatening conditions. The aim of this thesis was the evaluation of the prevalence of metabolic syndrome (MS) among survivors of allogeneic HSCT., Patients and Methods: We analyzed 74 patients with a median age at transplant of 35 years, who had been followed for a median of 5 years (2-23 years) after allogeneic HSCT. MS was defined according to the National Cholesterol Education Programs Adult Treatment Panel III (NCEP ATP III) criteria and by the International Diabetes Federation (IDF) definition., Results: The prevalence of MS among HSCT recipients was 40.5% applying the NCEP ATP III definition and 39.2% the IDF, a 2.02-fold increase compared to the general Slovak population. MS was more common in men. The most common MS features were abdominal obesity, hypertriglyceridemia and hypertension. The lowest prevalence of MS was in the age group of 20-29 years; and the highest prevalence in the age group of 60-69 years. The 10-year cumulative incidence of MS was 32.5%. The most significant risk factor for MS was total body irradiation, positive family history and age > 40 years at HSCT. Seven patients (9.45%) developed cardiovascular complications. The median 10-year general cardiovascular risk scores for males and females were found to be 13.3% and 6.68%, respectively., Conclusions: Detected increased prevalence of metabolic syndrome after allogeneic HSCT in patients surviving more than 2 years after this procedure may provide next stimulus to promote longer follow-up studies and to design of interventions to prevent late effects among survivors of serious hematologic diseases.

Competing Interests: IAgache is an Associate Editor Allergy and CTA. CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith‐Kline, advisory role in scibase. IA reports personal fees from Hikma, Roxall, Astra Zeneca, Menarini, UCB, Faes Farma, Sanofi, Mundipharma, Bial, Amgen, Stallergenes. SBA reports grants from TEVA, personal fees from TEVA, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, Mylan. VC reports personal fees from ALK, Allergy Therapeutics, LETI, Thermofisher, Merck, Astrazeneca, GSK. TC reports grants and personal fees from Stallergenes. PD reports personal fees from ALK‐Abello, Stallergenes‐Greer, Astra Zeneca, GlaxoSmithKline, Mylan, Sanofi. SD reports personal fees and non‐financial support from ALK Abello, personal fees from Adiga, Biomay, Allergopharma, Anergis, Allergy Therapeutics. TH reports personal fees from GSK, Mundipharma, Orion Pharma. SH reports other from ALK‐Abelló, other from ALK‐Abelló. EH reports personal fees from Sanofi, Novartis, GSK, AstraZeneca, Circassia, Nestlè Purina. JCI reports personal fees from Faes Farma, Laboratorios Casasco Argentina, Abbott de Ecuador, EuroFarma Argentina. MJ reports personal fees from ALK‐Abello, Allergopharma, Stallergenes, Anergis, Allergy Therapeutics, Circassia, Leti, Biomay, HAL, during the conduct of the study; personal fees from Astra‐Zeneka, GSK, Novartis, Teva, Vectura, UCB, Takeda, Roche, Janssen, Medimmune, Chiesi,. LK reports grants and personal fees from Allergopharma, MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quintiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. PK reports personal fees from Adamed, Berlin Chemie Menarini, Boehringer Ingelheim, AstraZeneca, Lekam, Novartis, Polpharma, GSK, Polpharma, Sanofi, teva. VK reports other from GSK, non‐financial support from Mylan, AstraZeneca, Dimuna, Norameda. SL reports personal fees from DBV, Sanofi Aventis, Allergopharma, ALK, Nutricia, Bencard. EM reports personal fees from Sanofi, Novartis, AstraZeneca and Chiesi. JM reports personal fees and other from SANOFI‐GENZYME & REGENERON, NOVARTIS, ALLAKOS, MITSUBISHI‐TANABE, MENARINI, UCB, ASTRAZENECA, GSK, MSD, grants and personal fees from MYLAN‐MEDA Pharma, URIACH Group. MO reports personal fees from Hycor Diagnostics, Thermo Fisher Phadia. YO reports personal fees from Torii Pharmaceutical Co., Ltd., Shionogi Pharmaceutical Co.,Ltd. OP received research grants from Inmunotek S.L., Novartis and MINECO and has received fees for giving scientific lectures or participation in Advisory Boards from: Allergy Therapeutics, Amgen, AstraZeneca, Diater, GlaxoSmithKline, S.A, Inmunotek S.L, Novartis, Sanofi‐Genzyme and Stallergenes. NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Pohl‐Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS. DPreports grants and personal fees from GlaxoSmithKline, personal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, personal fees and non‐financial support from Boehringer Ingelheim, non‐financial support from Philips. MR is on the Advisory board‐ A. Menarini ‐ Speaker ‐ Astra Zeneca, Novartis, Sanofi, Mylan. FSRreports speaker and advisory fees from AstraZeneca, Novartis, Sanofi, GSK, Teva and Lusomedicamenta. GR reports payment to his Institution from Allergo Pharma. BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. JS reports grants and personal fees from Sanofi, personal fees from GSK, Novartis, Astra Zeneca, Mundipharma, Faes Farma. GS reports personal fees from ALK, and leds on the BSACI Rhinitis Guidelines and lead for EUFOREA on Allergic Rhinitis. PSG reports personal fees from Allergopharma, ALK, grants from Bencard, grants and personal fees from Stallergenes. JS reports personal fees from Mylan, F2F events. ATB reports grants and personal fees from Teva, AstraZeneca, GSK Sanofi, Mundipharma, personal fees from Bial, Novartis. MJTreports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. MW reports personal fees from ALK‐Abello, Allergopharma, AstraZeneca, Bencard, Genzyme, GlaxoSmithKline, HAL Allergy, LETI, Meda Pharma, Novartis, Sanofi, Stallergenes, Teva. DW reports other from Optinose, ALK, Sanofi; past Co‐Chair of the Joint Task Force on Practice Parameters of the AAAAI and ACAAI. Second author of a recently published practice parameter on Rhinitis. MW reports other from Aralez (Medexus), Pediapharm, Pfizer, Astra Zeneca, GSK, Alk. MZ reports personal fees from Takeda. TZ reports and Organizational affiliations: Commitee member: WHO‐Initiative “Allergic Rhinitis and Its Impact on Asthma” (ARIA). Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI). Head: European Centre for Allergy Research Foundation (ECARF). Secretary General: Global Allergy and Asthma European Network (GA2LEN). Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). FIGURE 1Countries with Pocket Guide membersFIGURE 2Proposed Flow of Precision Medicine approach in allergic diseases. *examples of exceptions: Thunderstorm‐induced asthma, patient with moderate rhinitis and severe asthma during pollen seasonFIGURE 3Treatment algorithm using visual analogue scale (VAS) for adolescents and adults AIT, allergen immunotherapy; VAS, visual analogue scale.FIGURE 4Algorithm for AIT in asthma

No data are available regarding obesity and outcome in Chronic Lymphocytic Leukemia (CLL). We analyzed 263 patients from the AGMT CLL-8a Mabtenance trial for the impact of obesity. The trial included patients after rituximab-containing induction treatment in first or second line that had achieved at least a PR. A randomization to rituximab maintenance treatment (375 mg/m 2 q3 months for 2 years) vs observation was performed. In this cohort 22% of the patients (58/263) were classified as obese. The baseline response to induction treatment was inferior in obese patients with a lower CR rate (43.1% vs 60.5% in obese vs non-obese, P = 0.018) and with a lower rate of patients achieving MRD negativity after chemoimmunotherapy induction treatment (19.6% vs 35.8%, P = 0.02). The PFS outcome of obese patients was significantly worse in the observation group of the trial (24 vs 39 months median PFS, P = 0.03). However, in the rituximab maintenance group the outcome for obese vs non-obese was not different (P = 0.4). In summary, obesity was overall associated with a worse outcome of chemoimmunotherapy induction. However, rituximab maintenance treatment seems to be able to overcome this negative effect., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Candida glabrata is a second most common human opportunistic pathogen which causes superficial but also life-threatening systemic candidosis. According to the localisation of mannans and mannoproteins in the outermost layer of the cell wall, mannan detection could be one of the first steps in the cell recognition of Candida cells by the host innate immune system. Mannans from the cell wall provide important immunomodulatory activities, comprising stimulation of cytokine production, induction of dendritic cells (DCs) maturation and T-cell immunity. The model of DCs represents a promising tool to study immunomodulatory interventions throughout the vaccine development. Activated DCs induce, activate and polarise T-cell responses by expression of distinct maturation markers and cytokines regulating the adaptive immune responses. In addition, they are uniquely adept at decoding the fungus-associated information and translate it in qualitatively different T helper responses. We find out, that C. glabrata mannan is able to induce proliferation of splenocytes and to increase the production of TNF-α and IL-4. Next, increased the expression of co-stimulatory molecules CD80 and CD86 and the proportion of CD4+CD25+ and CD4+CD28+ T cells during in vitro stimulation of splenocytes. Reported results provide C. glabrata mannan capability to modulate cytokine production, DCs activation and antigen presentation activity, influencing T-cell phenotype in response to stimulation., (© FEMS 2019.)

The study is oriented at the in vitro evaluation of the immunobiological activity and efficacy of synthetically prepared isomeric pentasaccharides representing fragments of Aspergillus fumigatus cell-wall galactomannan and containing β-(1→5)-linked tetragalactofuranoside chain attached to O-6 ( GM-1 ) or O-3 ( GM-2 ) of a spacer-armed mannopyranoside residue. These compounds were studied as biotinylated conjugates which both demonstrated immunomodulatory activities on the RAW 264.7 cell line murine macrophages as in vitro innate immunity cell model. Immunobiological studies revealed time- and concentration-dependent efficient immunomodulation. The proliferation of RAW 264.7 macrophages was induced at higher concentration (100 µg/mL) of studied glycoconjugates and longer exposure (48 h), with more pronounced efficacy for GM-1 . The increase of proliferation followed the previous increase of IL-2 production. The cytokine profile of the macrophages treated with the glycoconjugates was predominantly pro-inflammatory Th1 type with significant increase of TNFα, IL-6, and IL-12 release for both glycoconjugates. The RAW 264.7 macrophages production of free radicals was not significantly affected by glycoconjugates stimulation. The phagocytic activity of RAW 264.7 cells was reduced following GM-1 treatment and was significantly increased after 24 h stimulation with GM-2 , contrary to 48 h stimulation. Moreover, the synthetically prepared galactomannoside derivatives have been evaluated as efficient serodiagnostic antigens recognized by specific Ig isotypes, and significant presence of specific IgM antibodies in serum of patients suffering from vulvovaginitis was observed.

Background: In many patients with chronic lymphocytic leukaemia requiring treatment, induction therapy with rituximab plus chemotherapy improves outcomes compared with chemotherapy alone. In this study we aimed to investigate the potential of rituximab maintenance therapy to prolong disease control in patients who respond to rituximab-containing induction regimens., Methods: In this randomised, international, multicentre, open-label, phase 3 clinical trial, we enrolled patients who had achieved a complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) to first-line or second-line rituximab-containing chemoimmunotherapy and randomly assigned them in a 1:1 ratio (central block randomisation in the electronic case report form system) to either intravenous rituximab 375 mg/m(2) every 3 months, or observation alone, for 2 years. Stratification was by country, line of treatment, type of chemotherapy added to the rituximab backbone, and degree of remission following induction. The primary endpoint was progression-free survival. Efficacy analysis was done in the intention-to-treat population. This is the final, event-triggered analysis. Final analysis was triggered by the occurrence of 92 events. This trial is registered with ClinicalTrials.gov, number NCT01118234., Findings: Between April 1, 2010, and Dec 23, 2013, 134 patients were randomised to rituximab and 129 to observation alone. Median observation times were 33·4 months (IQR 25·7-42·8) for the rituximab group and 34·0 months (25·4-41·9) for the observation group. Progression-free survival was significantly longer in the rituximab maintenance group (47·0 months, IQR 28·5-incalculable) than with observation alone (35·5 months, 95% CI 25·7-46·3; hazard ratio [HR] 0·50, 95% CI 0·33-0·75, p=0·00077). The incidence of grade 3-4 haematological toxicities other than neutropenia was similar in the two treatment groups. Grade 3-4 neutropenia occurred in 28 (21%) patients in the rituximab group and 14 (11%) patients in the observation group. Apart from neutropenia, the most common grade 3-4 adverse events were upper (five vs one [1%] patient in the observation group) and lower (three [2%] vs one [1%]) respiratory tract infection, pneumonia (nine [7%] vs two [2%]), thrombopenia (four [3%] vs four [3%]), neoplasms (five [4%] vs four [3%]), and eye disorders (four [3%] vs two [2%]). The overall incidence of infections of all grades was higher among rituximab recipients (88 [66%] vs 65 [50%])., Interpretation: Rituximab maintenance therapy prolongs progression-free survival in patients achieving at least a PR to induction with rituximab plus chemotherapy, and the treatment is well tolerated overall. Although it is associated with an increase in infections, there is no excess in infection mortality, suggesting that remission maintenance with rituximab is an effective and safe option in the management of chronic lymphocytic leukaemia in early treatment phases., Funding: Arbeitsgemeinschaft Medikamentöse Tumortherapie gemeinnützige GmbH (AGMT), Roche., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Specific allergen immunotherapy (AIT) is the only therapeutic method with positive impact on natural course of allergic disease - affecting clinical development (including the progression of rhinitis to asthma) and new sensitisations. The actual problem is the increasing number of patients manifesting poly-sensitivity in allergy skin tests and / or in specific IgE tests. Usually, AIT is not recommended in such individuals. The objective we are facing is that in many patients tested as poly-reactive, we have to distinguish in which cases it is a true polysensitization, and when it is due to cross-reactivity of specific IgE antibodies induced by panallergens. This may really determine when AIT may be an appropriate course of action. The article focuses on this problem in more detail, applying the long time Czech and Slovak experience with allergy testing and allergen immunotherapy.

In vitro evaluation of specific anti-Candida albicans sera antibodies based on synthetically prepared complement receptor 3-related protein (CR3-RP) mimicking the structure of native complement receptor 3 in a cohort of 72 patients with atopy and recurrent Candida vulvovaginitis (RVC) revealed effective humoral response against Candida CR3-RP. The most significant have been IgM and IgA isotype antibodies (33 and 47% positive cases, respectively). The quantitative evaluation of anti-CR3RP isotype antibodies was confronted with results of commercial ELISA anti-C. albicans antibodies diagnostics based on C. albicans cell wall mannan and β-glucan antigens, the most significant correlation being observed with anti-CR3-RP IgM and anti-β-D-glucan IgM (r(2) = 0.624) followed by isotype IgA (r(2) = 0.381). The immunogenicity and immunoreactivity of CR3RP antigen in RVC patients' sera had been evaluated with regard to the results reached by counterimmunoelectrophoresis and heterogeneous enzyme immunoassay. Obviously, synthetically prepared CR3-RP mimicking the Candida cell-wall-derived structure moiety represents a promising immunological tool not only for Candida serodiagnostics, but also prospectively for follow-up of targeted antifungal therapy and as promising Candida vaccine candidate., (© FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Introduction and Objective: The association between airborne pollen counts or duration of pollen season and allergy symptoms is not always distinguished. The purpose of this study was to examine the correlation between pollen exposure (annual total pollen quantity and main pollen season length) of selected allergenic plants in the atmosphere of Bratislava, and concentration of allergen-specific immunoglobulin E (sIgE) in serum of patients with seasonal allergy during 2002-2003., Materials and Methods: The concentration of pollen was monitored by a Burkard volumetric pollen trap. At the same time, 198 pollen allergic patients were testing to determine the values of sIgE antibodies against selected pollen allergens; a panel of 8 purified allergens was used., Results: The highest percentages of sensitization were detected for Poaceae and Ambrosia pollen allergens. The most abundant airborne pollen types were Urticaceae, Betula, Populus, Fraxinus, Pinus and Poaceae. The length of the pollen season varied. The longest pollen season was that of the Plantago - 105 days, and the shortest, Corylus - 20 days. A significant correlation was found between annual total pollen quantity and median sIgE values, especially in 2002., Conclusions: A strong and significant positive correlation was observed between pollen counts, excluding Betula, and sIgE levels in both analysed years. The correlation was weaker and negative in the case of length of pollen season and sIgE values.

A retrospective review of the published literature identified several hundred adverse reactions (e.g. nausea, chills, cardiac arrhythmias, neurological symptoms and respiratory arrest) associated with the transplantation of stem cells cryopreserved with dimethyl sulfoxide. The occurrences of these are generally accepted as commonplace, as the majority of reactions are transient, whilst a few patients may require clinical treatment. This exploratory study is a collation of the historical data and the expectations for the notification of serious adverse reactions. Outline information is presented on the development of related European Directives, some technical aspects of dimethyl sulfoxide and the sequential stages of preservation and administration.