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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.)

Bone marrow (BM) is one of the sources of hematopoietic stem cells used for allogeneic transplantation. In this retrospective study, we analysed bone marrow harvests in 216 healthy donors over a ten-year period (2007–2017). Larger volumes of bone marrow were obtained from male compared to female donors (1300 ml vs. 1100 ml) due to their higher body weight, resulting in a higher number of nucleated cells (156 vs. 124 x 106 TNC, ns). The total yield was dependent on the volume of marrow (p < 0.0001) and donor weight (p = 0.01). Suboptimal grafts containing ≤ 2.0 x 108 TNC/kg (recipient) were collected in 6 % of cases, always with significant differences of weight between donor and recipient (median 20 kg). All donors underwent preoperative autologous blood donation (PAD). The initial haemoglobin level of 153 g/L (male donors) and 135 g/L (female donors) decreased by about 8 g/L after preoperative blood donation and by 23 g/L after bone marrow harvest. Auto-transfusion was administered to 70 % of donors, 30 % of the units remained unused. Evaluation of the risk of reaching transfusion threshold (<115 g/L males, < 105 g/L females) revealed that donors with initial haemoglobin level above 145 g/L and those weighing more than 75 kg have a minimal risk of requiring blood substitution (about 10 %). The incidence of adverse events associated with bone marrow harvests was low (5 %) and none of these were classified as serious. The analysis proved that the amount of nucleated cells harvested and substitution requirements are determined by donor parameters (weight, haemoglobin level) and recipient parameters (weight). Given the changing policy to auto-transfusion during bone marrow collection, the issue of balancing the benefits and risks of administering preoperative autologous transfusion should be addressed. [ABSTRACT FROM AUTHOR]

Determination of CD34+ cells by flow cytometry is a basic method for assessing the quality of hematopoietic stem cell grafts and for planning their collection by leukapheresis. This method is based on multiparameter flow cytometry and is well-standardized internationally. The EQA program for CD34 + quantification has been available in the Czech and the Slovak Republic since 2010 with more than 20 laboratories involved. Evaluation of the 8-year experience has shown an excellent long-term success of participating laboratories ranging between 80–100 %, with sporadic fluctuations. Some of the participants who have been involved in the program from the beginning, achieve even 90% success rates. Reproducibility of measurement results is highly dependent on the amount of CD34+ cells in the sample. CV oscillates around 10 % if the CD34+ count is 10/μL or higher and increases by dozens of percent below this level. The program plays an important role in harmonizing CD34+ determination between transplant centres and increases the likelihood of obtaining accurate and comparable results. [ABSTRACT FROM AUTHOR]

Cryopreservation of haematopoietic stem cells represents a common method used to support autologous transplantation or to process allogeneic collections. Most transplant centres are struggling with an increasing number of unused long-term stored transplants on one hand and the absence of generally accepted rules for their disposal on the other. The goal of the recommendations is to offer a set of measures to ensure the long-term storage and eventual disposal of cryopreserved products and to try and harmonize these at national level. [ABSTRACT FROM AUTHOR]

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.)

An increasing number of cancer patients are being admitted to the intensive care and high dependency units due to the rising incidence of solid and/or haematological malignancies together with an expanding range of therapeutic options and improved survival of these patients. The reasons for admission are the potentially life-threatening cancer-related complications and/or treatment-associated side-effects or eventual co-morbidities. Epidemiology, indication criteria, extension of treatment, prognosis of the acute disease and changes applied to the general prognosis as a consequence of the critical illness are some of the most common and frequently unanswered questions the intensivists need to examine, and they are discussed within this review. [ABSTRACT FROM AUTHOR]

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.)

Multiple myeloma (MM) is a disease which remains incurable. One of the main reasons is a weakened immune system that allows MM cells to survive. Therefore, the current research is focused on the study of immune system imbalance in MM to find the most effective immunotherapy strategies. Aiming to identify the key points of immune failure in MM patients, we analysed peripheral lymphocytes subsets from MM patients (n = 57) at various stages of the disease course and healthy individuals (HI, n = 15) focusing on T, NK, iNKT, B cells and NK-cell cytokines. Our analysis revealed that MM patients exhibited immune alterations in all studied immune subsets. Compared to HI, MM patients had a significantly lower proportion of CD4 + T cells (19.55% vs. 40.85%; p < 0.001) and CD4 + iNKT cells (18.8% vs. 40%; p < 0.001), within B cells an increased proportion of CD21LCD38L subset (4.5% vs. 0.4%; p < 0.01) and decreased level of memory cells (unswitched 6.1% vs. 14.7%; p < 0.001 and switched 7.8% vs. 11.2%; NS), NK cells displaying signs of activation and exhaustion characterised by a more than 2-fold increase in SLAMF7 MFI (p < 0.001), decreased expression of NKG2D (MFI) and NKp46 (%) on CD16 + 56 + and CD16 + 56- subset respectively (p < 0.05), Effective immunotherapy needs to consider these immune defects and monitoring of the immune status of MM patients is essential to define better interventions in the future., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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 standard of care in multiple myeloma (MM) consists of induction chemotherapy followed by autologous stem cell transplant (autoSCT), but this setting doesn't present curative potential. Despite advances in new, efficient, and targeted drugs, allogeneic transplant (aloSCT) remains the modality with curative potential in MM. With the knowledge of high mortality and morbidity related to the treatment in comparison to treatment with novel drugs, there is no consensus in the indication of aloSCT in MM, also the choice of ideal patients profiting from this method is difficult. Therefore, we performed a retrospective unicentric study of 36 unselected consecutive patients transplanted for MM in the University Hospital in Pilsen between the years 2000-2020 in order to define possible variables influencing survival. The median age of the patients was 52 years (38-63) and the distribution of MM subtypes was standard. The majority of the patients were transplanted in the relapse setting, 3 (8.3%) patients in the 1st line setting, and in 7 (19%) patients elective auto-alo tandem transplant was performed. 18 patients (60% of patients with available cytogenetics (CG) had high-risk disease. 12 (33.3%) patients were transplanted with chemoresistant disease (at least PR not reached). With a median follow-up of 85 months, we observed median overall survival (OS) of 30 months (range 10-60) and median progression-free survival (PFS) of 15 months (11-175). 1- and 5-year Kaplan Meier survival probabilities for OS were 55% and 30.5% respectively. During the follow-up, 27 (75%) patients died, 11 (35%) due to treatment-related mortality (TRM), and 16 patients (44%) due to a relapse. 9 (25%) patients were still alive, 3 (8.3%) of them with complete remission (CR), and 6 (16.7%) patients with relapse/progression. Altogether 21 (58%) of the patients relapsed/progressed with a median of 11 months (3-175). Incidence of clinically significant acute graft versus host disease (aGvHD gr. >II) was low (8.3%) and extensive chronic GvHD (cGvHD) developed in 4 patients (11.1%). Univariant analysis proved marginal statistical significance in disease status before aloSCT (chemosensitive × chemoresistant) for OS, favoring patients with the chemosensitive disease (HR 0.43, 95% CI 0.18-1.01, p=0.05), there was no significant impact of high-risk cytogenetics (CG) on survival. No other analyzed parameter was found to be significant. Our findings support the conclusion that aloSCT is able to overcome high-risk CG and that aloSCT still remains a valid treatment choice with acceptable toxicity in well-selected high-risk patients with curative potential, even though often with active disease, but not derogating the quality of life significantly.

Background: Older patients with AML/MDS have a poor prognosis with alloHCT as the only curative option. However alloHCT is challenging given its high TRM. Recently, a composite endpoint of GRFS was proposed to define transplant success. A single centre retrospective analysis was performed to determine the main variables influencing GRFS., Patients and Methodsmethods: 91 consecutive patients≥ 60 years (median 64 years, range 60-74) with AML/MDS who received reduced-intensity alloHCT during 2001-2017 analysed. Disease risk index (DRI) at HCT was low/intermediate in 47pts (52%) and high in 44 pts (48%)., Results: After median follow-up for survivors of 56 months (range 7-144), 37 (40.6%) patients were alive. The OS, LFS and GRFS were 61.4%, 58.1%, 49.1% at 1 year and 35.5%, 32.3% and 23.1% at 5 years, respectively. The 1-year and 5-year incidences of NRM and relapse were 26.9%, 21.3% and 47.9% and 35.4%, respectively. In univariate analysis, high DRI was the strongest factor for worse OS (HR 2.121; p = 0.049), LFS (HR 1.924; p = 0.0123) and GRFS (HR 2.319; p = 0.0005). The donor age ≥ 62 years had a negative impact on OS (HR 2.110; p = 0.0345) and GRFS (HR 2.014; p = 0.0341). High DRI (HR 2.652; p = 0.0003) and donor age (HR 2.304; p = 0.0257) retained its significance in multivariate analysis for GRFS., Conclusion: A significant portion of older patients with myeloid malignancies survive alloHCT without experiencing GRFS event with DRI as the main determinant of outcome. Negative impact of donor age≥ 62 years suggests preference of a young donor, regardless of being related or unrelated., Competing Interests: Declarations of interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Patients with chronic lymphocytic leukemia (CLL) have a high risk of poor outcomes related to coronavirus disease 2019 (COVID-19). This multicenter cohort study evaluated the impact of COVID-19 infection on the population of CLL patients in the Czech Republic. Between March 2020 and May 2021, 341 patients (237 males) with CLL and COVID-19 disease were identified. The median age was 69 years (range 38-91). Out of the 214 (63%) patients with the history of therapy for CLL, 97 (45%) were receiving CLL-directed treatment at diagnosis of COVID-19: 29% Bruton tyrosine kinase inhibitor (BTKi), 16% chemoimmunotherapy (CIT), 11% Bcl-2 inhibitor, and 4% phosphoinositide 3-kinase inhibitor. Regarding the severity of COVID-19, 60% pts required admission to the hospital, 21% pts were admitted to the intensive care unit (ICU), and 12% received invasive mechanical ventilation. The overall case fatality rate was 28%. Major comorbidities, age over 72, male gender, CLL treatment in history, CLL-directed treatment at COVID-19 diagnosis were associated with increased risk of death. Of note, concurrent therapy with BTKi compared to CIT was not associated with better outcome of COVID-19., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Preoperative autologous blood donation (PAD) in bone marrow (BM) donors is performed to meet potential post-harvest transfusion needs and to avoid the risk of allogeneic transfusions. We reviewed retrospectively bone marrow harvests in 216 healthy donors during a ten-year period to determine the use of autologous blood. All donors except four had undergone PAD. The initial hemoglobin level of 153 g/L (male donors) and 135 g/L (female donors), respectively, decreased by about 8 g/L after preoperative blood donation and by 23 g/L after bone marrow harvest (medians). Autologous blood was administered to 70% of donors, 30% of the units remained unused. The evaluation of the risk of reaching transfusion threshold (<115 g/L males, <105 g/L females) revealed that donors with initial hemoglobin above 145 g/L and those weighing above 75 kg have minimal risk of requiring blood substitution (about 10%). A larger volume of bone marrow was obtained from male compared to female donors (1300 vs. 1100 mL) because of their higher body weight, which resulted in a higher number of procured nucleated cells (362 vs. 307 × 10 6 /kg TNC, ns). The donor-recipient weight difference predicted the probability of sufficient collection. Only 1.5% of donors weighing ≥ 20 kg more than recipients failed to reach ≥3 × 10 8 /kg TNC recipient. Our findings affirm previous data that PAD is unnecessary for healthy marrow donors and may be indicated individually after considering the pre-collection hemoglobin level, donor and recipient weight, and expected blood loss. Reasonable substitution cut-offs have to be set together with clinical symptom evaluation. The effective use of PAD also requires an adequate time interval between PAD and BM harvest.

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p < 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-β, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine.

Killer-immunoglobulin-like receptors (KIRs) are critical natural killer (NK) cell regulators. The expression of KIRs is a dynamic process influenced by many factors. Their ligands-HLA(Human Leukocyte Antigen) class I molecules-are expressed on all nucleated cells that keep NK cells under control. In hematopoietic stem cell transplantation (HSCT), NK cells play an essential role in relapse protection. In the presented pilot study, we characterized the dynamic expression of inhibitory KIRS (iKIRs), which protect cells against untoward lysis, in donors and patients during the first three months after HSCT using flow cytometry. The expression of all iKIRs was highly variable and sometimes correlated with patients' clinical presentation and therapy regiment. Cyclophosphamide (Cy) in the graft-versus-host disease (GvHD) prevention protocol downregulated KIR2DL1 to just 25% of the original donor value, and the FEAM (Fludarabine + Etoposid + Ara-C + Melphalan) conditioning protocol reduced KIR2DL3. In lymphoid neoplasms, there was a slightly increased KIR2DL3 expression compared to myeloid malignancies. Additionally, we showed that the ex vivo activation of NK cells did not alter the level of iKIRs. Our study shows the influence of pre- and post-transplantation protocols on iKIR expression on the surface of NK cells and the importance of monitoring their cell surface.

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.)