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Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Transfusiology & Haematology Today / Transfuze a Hematologie Dnes is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Studies on human telomeres have established that telomeres exert a significant influence on lifespan and health of organisms. However, recent research has indicated that the original idea that telomeres affect lifespan in a universal and central manner across all eukaryotic species is an oversimplification. Indeed, findings from a variety of animal species revealed that the role of telomere biology in aging is more subtle and intricate than previously recognized. Here, we show how telomere biology varies depending on the taxon. We also show how telomere biology corresponds to basic life history traits and affects the life table of a species and investments in growth, body size, reproduction, and lifespan; telomeres are hypothesized to shape evolutionary perspectives for species in an active but complex manner. Our evaluation is based on telomere biology data from many examples from throughout the animal kingdom that vary according to the degree of organismal complexity and life history strategies., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Idelalisib (idela), a phosphatidylinositol 3-kinase inhibitor, and ibrutinib, a Bruton tyrosine kinase inhibitor, were the first oral targeted agents approved for relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). However, no randomised trials of idelalisib plus rituximab (R-idela) versus ibrutinib have been conducted. Therefore, we performed a real-world retrospective analysis of patients with R/R CLL treated with R-idela (n = 171) or ibrutinib (n = 244). The median age was 70 versus 69 years, with a median of two previous lines. There was a trend towards higher tumour protein p53 (TP53) aberrations and complex karyotype in the R-idela group (53% vs. 44%, p = 0.093; 57% vs. 46%, p = 0.083). The median progression-free survival (PFS) was significantly longer with ibrutinib (40.5 vs. 22.0 months; p < 0.001); similarly to overall survival (OS; median 54.4 vs. 37.7 months, p = 0.04). In multivariate analysis, only PFS but not OS remained significantly different between the two agents. The most common reasons for treatment discontinuation included toxicity (R-idela, 39.8%; ibrutinib, 22.5%) and CLL progression (27.5% vs. 11.1%). In conclusion, our data show significantly better efficacy and tolerability of ibrutinib over R-idela in patients with R/R CLL treated in routine practice. The R-idela regimen may still be considered a reasonable option in highly selected patients without a suitable treatment alternative., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

The anatomical, physiological, and behavioral characteristics of honey bees are affected by the season as well as division of labor. In this study, we examined the structure, ultrastructure, and gene expression of fat body cells in both long-lived winter and short-lived summer worker bees (the youngest stage of hive bees and forager bees). In contrast to hive bees, foragers and winter bees have a higher metabolism due to intensive muscle activity during their flight (foragers) or endothermic heat production (winter bees). These workers differ from hive bees in the biology of their mitochondria, peroxisomes, and lysosomes as well as in the expression of the genes involved in lipid, carbohydrate, amino acid metabolism, insulin, and TGF- β signaling. Additionally, the expression of genes related to phospholipid metabolism was higher in the hive bees. However, we found no differences between workers in the expression of genes controlling cell organelles, such as the Golgi apparatus, endoplasmic reticulum, ribosomes, nucleus, and vacuoles, as well as genes for DNA replication, cell cycle control, and autophagy. Furthermore, lysosomes, autophagic processes and lipofuscin particles were more frequently observed in winter bees using electron microscopy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Therapeutic options used to be very limited for treatment-naïve elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) before the introduction of chemo-immunotherapy. Because dose-reduced fludarabine-based regimens yielded promising results, the Czech CLL Study Group initiated a prospective observational study to assess safety and efficacy of low-dose fludarabine and cyclophosphamide combined with rituximab (FCR) in elderly/comorbid patients. Between March 2009 and July 2012, we enrolled 107 patients considered ineligible for full-dose FCR (median age, 70 years; median Cumulative Illness Rating Scale score, 5; median creatinine clearance, 69 ml/min). Notably, 77% patients had unfavourable biological prognosis [unmutated immunoglobulin heavy-chain variable-region gene (IGHV), 74%; deletion 17p, 9%). Fludarabine was reduced to 12 mg/m 2 intravenously (iv) or 20 mg/m 2 orally on days 1-3 and cyclophosphamide to 150 mg/m 2 iv/orally on days 1-3. Grade 3-4 neutropenia occurred in 56% of the patients, but there were serious infections in only 15%. The median progression-free survival was 29 months, but was markedly longer in patients with mutated IGHV (median 53 months), especially in absence of del 11q or 17p (median 74 months). Low-dose FCR is a well-tolerated and effective first-line regimen for selected elderly/comorbid patients with CLL/SLL with favourable biology. The study was registered at clinicaltrials.gov (NCT02156726)., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Most patients with chronic lymphocytic leukaemia (CLL) are nowadays diagnosed without any symptoms and do not require therapy. A prognostic score identifying patients within this large group who are at high risk of disease progression would be highly beneficial. The recently published International Prognostic Score for Early asymptomatic patients (IPS-E) uses combination of absolute lymphocyte count (ALC) >15 × 10 9 /l, palpable lymphadenopathy, and unmutated immunoglobulin heavy-chain variable-region (IGHV) gene to predict the time to first-line therapy (TTFT). Patients at low, intermediate, and high risk had estimated 5-year TTFT of 8%, 28%, and 61%. We performed an external validation of the IPS-E score using an unselected, consecutive group of 130 Binet A patients. The 5-year TTFT was 11%, 36%, and 78% (C-statistic 0·74). Furthermore, we propose an alternative system (AIPS-E) using cytogenetic aberrations instead of palpable lymphadenopathy. This system yielded 5-year TTFT of 14%, 40%, and 72%. These results were externally validated in 388 Binet A patients from five Czech centres; the 5-year TTFT was 16%, 37%, and 80% (C-statistic 0·74). In conclusion, we have successfully validated the IPS-E score for patients with early stage CLL. In addition, we propose a modified scoring system, the AIPS-E, combining IGHV, fluorescence in situ hybridisation, and ALC., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)

In honeybees (Apis mellifera), the rate of aging is modulated through social interactions and according to caste differentiation and the seasonal (winter/summer) generation of workers. Winter generation workers, which hatch at the end of summer, have remarkably extended lifespans as an adaptation to the cold season when the resources required for the growth and reproduction of colonies are limited and the bees need to maintain the colony until the next spring. In contrast, the summer bees only live for several weeks. To better understand the lifespan differences between summer and winter bees, we studied the fat bodies of honeybee workers and identified several parameters that fluctuate in a season-dependent manner. In agreement with the assumption that winter workers possess greater fat body mass, our data showed gradual increases in fat body mass, the size of the fat body cells, and Vg production as the winter season proceeded, as well as contrasting gradual decreases in these parameters in the summer season. The differences in the fat bodies between winter and summer bees are accompanied by respective increases and decreases in telomerase activity and DNA replication in the fat bodies. These data show that although the fat bodies of winter bees differ significantly from those of summer bees, these differences are not a priori set when bees hatch at the end of summer or in early autumn but instead gradually evolve over the course of the season, depending on environmental factors.

Until recently, a combination of anti-CD20 antibody plus less intensive chemotherapy was a standard of care in elderly population with previously untreated chronic lymphocytic leukemia (CLL). The aim of this observational study was to retrospectively assess efficacy and safety of obinutuzumab + chlorambucil (G-Clb), rituximab + chlorambucil (R-Clb), and bendamustine + rituximab (BR) given as the frontline therapy within routine practice. The final analyzed dataset included 398 consecutive CLL patients from 10 hematology centers cooperating within the Czech CLL Study Group: 63 treated with G-Clb, 78 with R-Clb, and 257 with BR. There were no significant differences in prognostic and predictive markers among the groups. On the contrary, median age at the start of therapy and cumulative illness rating scale (CIRS) score was significantly higher in R-Clb group. Obinutuzumab plus chlorambucil regimen was preferably offered to elderly patients (compared to BR) with less severe comorbidities and lower CIRS score (compared to R-Clb). A time period when a treatment was indicated had also a strong impact on the choice of the regimen. The overall response rate reached 76% (30% complete remissions, CRs) in G-Clb, 75% (22% CRs) in R-Clb, and 85% (47% CRs) in BR group. Median event-free survival was 49.0 months for G-Clb, 20.3 months for R-Clb, and 37.0 months for BR group. Neutropenia grade ≥ 3 developed in 43% of G-Clb, 31% of R-Clb and in 49% of BR patients, grade ≥ 3 infections were recorded in 17% of G-Clb, 6.4% of R-Clb, and 17% of BR patients. In conclusion, real-world therapeutic activity of G-Clb appears to be at least comparable to prospective clinical trial data. R-Clb yields relatively good results in very old and severely comorbid patients., (© 2020 John Wiley & Sons Ltd.)

Patients with chronic lymphocytic leukemia have disrupted cellular and humoral immunity with quantitative and qualitative impairment of the cells of the immune system. Immunity disbalance leads to increased incidence of infections and autoimmune cytopenias. Supportive care for chronic lymphocytic leukemia focuses on prevention and treatment of these complications and consists of antimicrobial prophylaxis, substitution of immunoglobulins, immunosuppressive therapy, growth factors and blood transfusions.

The significance of chromosomal translocations (CTRAs) and karyotype complexity (KC) in chronic lymphocytic leukemia (CLL) remains uncertain. To gain insight into these issues, we evaluated a series of 1001 CLL cases with reliable classic cytogenetic data obtained within 6 months from diagnosis before any treatment. Overall, 320 cases were found to carry ≥ 1 CTRAs. The most frequent chromosome breakpoints were 13q, followed by 14q, 18q, 17q, and 17p; notably, CTRAs involving chromosome 13q showed a wide spectrum of translocation partners. KC (≥ 3 aberrations) was detected in 157 cases and significantly (P < 0.005) associated with unmutated IGHV genes and aberrations of chromosome 17p. Furthermore, it was identified as an independent prognostic factor for shorter time-to-first-treatment. CTRAs were assigned to two categories (i) CTRAs present in the context of KC, often with involvement of chromosome 17p aberrations, occurring mostly in CLL with unmutated IGHV genes; in such cases, we found that KC rather than the presence of CTRAs per se negatively impacts on survival; (ii) CTRAs in cases without KC, having limited if any impact on survival. On this evidence, we propose that all CTRAs in CLL are not equivalent but rather develop by different processes and are associated with distinct clonal behavior., (Copyright © 2013 Wiley Periodicals, Inc.)

Chronic lymphocytic leukemia (CLL) patients may acquire new chromosome abnormalities during the course of their disease. Clonal evolution (CE) has been detected by conventional chromosome banding (CBA), several groups also confirmed CE with fluorescence in situ hybridization (FISH). At present, there are minimal prospective data on CE frequency determined using a combination of both methods. Therefore, the aim of our study was to prospectively assess CE frequency using a combination of FISH and CBA after stimulation with CpG oligonucleotides and interleukin-2. Between 2008 and 2012, we enrolled 140 patients with previously untreated CLL in a prospective trial evaluating CE using FISH and CBA after stimulation. Patients provided baseline and regular follow-up peripheral blood samples for testing. There was a median of 3 cytogenetic examinations (using both methods) per patient. CE was detected in 15.7% (22/140) of patients using FISH, in 28.6% (40/140) using CBA, and in 34.3% (48/140) of patients by combining both methods. Poor-prognosis CE (new deletion 17p, new deletion 11q or new complex karyotype) was detected in 15% (21/140) of patients and was significantly associated with previous CLL treatment (p=0.013). CBA provides more complex information about cytogenetic abnormalities in CLL patients than FISH and confirms that many patients can acquire new abnormalities during the course of their disease in a relatively short time period., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: The impact of modern prognostic markers on clinical course of chronic lymphocytic leukaemia (CLL) in everyday practice has been not yet well defined, especially in large series of patients. Therefore, the goal of this study was to assess the influence of conventional as well as modern prognostic factors on overall survival (OS) and time to therapy (TTT) of patients with CLL., Methods: We retrospectively analysed data of all patients consecutively entered into the databases of five large academic centres in the Czech Republic. The total of 1300 patients was included in the analysis., Results and Conclusion: Through the use of uniparametric analysis, it was determined that gender, clinical stage Rai II-IV, unmutated IgVH status, deletion 17p (for both 5% and 20% cut-off), deletion 11q, ZAP-70 positivity and high expression of CD38 had significant negative influence on OS. TTT was significantly influenced by gender, Rai stage, IgVH status, deletion 11q, deletion 17p, deletion 13q and CD38 expression. Multiparametric analysis revealed that OS was significantly influenced by gender, age, IgVH status and deletion 17p. If only patients who died of CLL were included, gender, age, Rai stage, IgVH status and deletion 17p had significant influence on OS. Based on our results, the examination of biological prognostic markers can give an insight into the possible disease evolution in daily clinical practice. Biological prognostic markers are, however, not ready (maybe except deletion 17p in younger patients) to be used for guidance of therapy at least outside of clinical trials., (© 2011 John Wiley & Sons A/S.)

Backgrounds: Patients with multiple myeloma have a high risk of venous thromboembolism (VTE), especially during the induction chemotherapy. The aim of our observational study was to determine the impact of prophylaxis with low molecular weight heparin (LMWH) on the incidence of thromboembolic complications., Patients and Methods: We analyzed the incidence of thromboembolic events in 258 patients treated with induction chemotherapy containing vincristin, doxorubicin or idarubicin, and dexamethasone, followed by stimulation chemotherapy with cyclophosphamide and G-CSF, and high-dose chemotherapy with melphalan. Two groups of these patients were compared based on the practice of thromboprophylaxis. Patients in the first group (Control, n = 140) were either not treated or treated with a short duration of anticoagulation therapy while the patients in the second group (Prophylactic, n = 118) underwent standard prophylaxis with LMWH throughout the entire period of induction chemotherapy. A total of 102 patients were selected for a close monitoring of the prophylactic effect of different LMWH doses and to be compared to patients without treatment., Results: Standard prophylaxis with LMWH significantly (p < 0.007) lowered a risk of VTE when compared to patients without such prophylaxis (3.4% versus 12.9%, respectively). Furthermore, analysis of the subgroup of 102 patients revealed that higher LMWH doses (> 70 IU/kg per day) achieved full prophylaxis in 28 patients while lower doses were less effective leading to DVT in 3 (7.7%) out of 39 patients. In contrast, VTE was diagnosed in 5 (14.3%) out of 35 patients without any LMWH prophylaxis., Conclusion: Prophylaxis with LMWH leads to a significant reduction of the risk of thromboembolic complications during the induction chemotherapy in patients suffering from MM. The prophylactic effect of LMWH is dose-dependent.

Backgrounds: The Ann Arbor system is typically used for the staging of Non-Hodgkin's lymphomas. This classification was nevertheless originally developed in the 1970s for Hodgkin's lymphoma, a disease usually confined to the lymph nodes with less frequent dissemination to extralymphatic organs/tissues and extremely rare primary extranodal involvement. Non-Hodgkin's lymphomas, however, are more often associated with extralymphatic involvement and primary extranodal lymphomas are relatively common (approximately 1/3 of cases). Therefore, the value of the Ann Arbor staging system appears to be limited in these cases. An analysis of data from centres participating within the Czech Lymphoma Study Group showed that staging of Non-Hodgkin's lymphomas with extranodal involvement is not uniform., Design: At the end of 2009, a draft for a Non-Hodgkin's lymphomas staging system was put forward for use by the lymphoma register of the Czech Lymphoma Study Group with special regard paid to the involvement of extralymphatic organs/tissues. This draft was further refined following comments from members of the Czech Lymphoma Study Group committee and the final form was accepted at the meeting of the Czech Lymphoma Study Group committee in January 2010., Results: A consensus was reached at the meeting of the Czech Lymphoma Study Group committee regarding the staging of various combinations of nodal and extranodal involvement. For the purpose of suitable staging and appropriate treatment intensity, extranodal organs were divided into "major"--liver, lungs, bones, mesothelium (pleura, peritoneum, pericardium) and soft tissues. All other organs were defined as "minor"., Conclusion: The Ann Arbor staging system is suitable for the staging of Non-Hodgkin's lymphomas with lymph node/lymphatic tissue involvement. As regards the extralymphatic spread of the disease or primary extranodal lymphomas, this classification should rather be adapted to practical needs. The validity of the updated classification system will be assessed in both prospective and retrospective Czech Lymphoma Study Group studies.

Deletion of TP53 gene, under routine assessment by fluorescence in situ hybridization analysis, connects with the worst prognosis in chronic lymphocytic leukemia (CLL). The presence of isolated TP53 mutation (without deletion) is associated with reduced survival in CLL patients. It is unclear how these abnormalities are selected and what their mutual proportion is. We used methodologies with similar sensitivity for the detection of deletions (interphase fluorescence in situ hybridization) and mutations (yeast functional analysis) and analyzed a large consecutive series of 400 CLL patients; a subset of p53-wild-type cases (n = 132) was screened repeatedly during disease course. The most common type of TP53 inactivation, ie, mutation accompanied by deletion of the remaining allele, occurred in 42 patients (10.5%). Among additional defects, the frequency of the isolated TP53 mutation (n = 20; 5%) and the combination of 2 or more mutations on separate alleles (n = 5; 1.3%) greatly exceeded the sole deletion (n = 3; 0.8%). Twelve patients manifested defects during repeated investigation; in all circumstances the defects involved mutation and occurred after therapy. Monoallelic defects had a negative impact on survival and impaired in vitro response to fludarabine. Mutation analysis of the TP53 should be performed before each treatment initiation because novel defects may be selected by previous therapies.

Unlabelled: Alemtuzumab in chronic lymphocytic leukemia treatment: retrospective analysis of outcome according to cytogenetics, Summary: Alemtuzumab is effective in B-cell chronic lymphocytic leukemia (CLL) with 17p deletion, which responds poorly to chemotherapeutic agents. Our retrospective study evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced CLL, categorized by cytogenetic profile. Data were collected from 74 consecutive who had received alemtuzumab. Median of previous therapies was 2. The incidence of cytogenetic abnormalities was: trisomy 12, 10%; 13q deletion, 13%; 11q deletion 25%; 17p deletion, 26%; none of these, 26%. The overall response rate was 65% (11% complete remission, 54% partial remission) in the whole cohort. From start of alemtuzumab therapy, median progression-free survival was 217 days, median time to alternative treatment was 287 days, and median overall survival was 999 days in the total cohort, respectively. Alemtuzumab was effective across all cytogenetic categories evaluated. There were no statistically significant differences between subgroups in the level of efficacy.

Anticoagulant therapy is one of the most common forms of medical intervention. It is the mainstay of prevention and treatment of thrombotic events. Omission of adequate anticoagulant prophylaxis at least for moderate-risk and high-risk patients is a widely recognized medical error. Bleeding is one of the most feared complications of anticoagulant therapy, and is a risk of all anticoagulants. Whereas unfractionated heparin and warfarin, the oldest and most widely used anticoagulants, have specific antidotes for their anticoagulant effect, many of the newer agents (direct and indirect inhibitors of coagulation factors Xa and/or IIa) do not have specific antidotes to reverse their actions. The use of novel anticoagulants is further complicated by a lack of easily available laboratory tests to measure their levels and thereby optimize their benefit and safety in clinical practice. In this review, we evaluate the risk of bleeding associated with current anticoagulants, review the data available on current and experimental agents used for the reversal of anticoagulation, and provide recommendations for the management of major bleeding associated with anticoagulant therapy and for the management of asymptomatic overdosing of the anticoagulants.