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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]

Mesenchymal stem cells (MSCs) have been reported to improve survival of cardiomyocytes (CMCs) and overall regeneration of cardiac tissue. Despite promising preclinical results, interactions of MSCs and CMCs, both direct and indirect, remain unclear. In this study, porcine bone marrow MSCs and freshly isolated porcine primary adult CMCs were used for non-contact co-culture experiments. Morphology, viability and functional parameters of CMCs were measured over time and compared between CMCs cultured alone and CMCs co-cultured with MSCs. In non-contact co-culture, MSCs improved survival of CMCs. CMCs co-cultured with MSCs maintained CMCs morphology and viability in significantly higher percentage than CMCs cultured alone. In viable CMCs, mitochondrial respiration was preserved in both CMCs cultured alone and in CMCs co-cultured with MSCs. Comparison of cellular contractility and calcium handling, measured in single CMCs, revealed no significant differences between viable CMCs from co-culture and CMCs cultured alone. In conclusion, non-contact co-culture of porcine MSCs and CMCs improved survival of CMCs with a sufficient preservation of functional and mitochondrial parameters. [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.)

Background: Patients with internal tandem duplication in fms-related tyrosine kinase receptor gene 3 (FLT3-ITD)-mutated acute myeloid leukemia (AML) have a dismal prognosis and the only curative option seems to be allogeneic stem cell transplantation (alloSCT). However, its timing is still matter of debate., Patients and Methods: We retrospectively analyzed 73 consecutive AML patients with FLT3-ITD (median age 53, range 20-68 years) allografted with consistent policy to try to refer them all for upfront alloSCT in first complete remission (CR1)., Results: With a median follow-up of 44 (range, 5-135) months the 5-year overall survival (OS)/disease-free survival (DFS) probabilities were 49%/47%. The cumulative incidence of relapse and nonrelapse mortality (NRM) were 37% and 14%, respectively. The estimated 5-year OS for patients who received transplantation in CR1 was 62% versus 0% for patients who received transplantation beyond CR1. Multivariable analysis identified stem cell transplantation beyond CR1 as the key factor for poor OS (hazard ratio [HR], 5.41; P < .0001), DFS (HR, 4.41; P = .0002), and high relapse incidence (HR, 8.08; P < .0001). Acute graft versus host disease Grade ≥3 predicted higher NRM (HR, 3.80; P = .059) as well as inferior OS (HR, 2.04; P = .0079). No association of patient age, nucleophosmin status, donor type, conditioning, and other variables on the survival was detected., Conclusion: AlloSCT should be regarded with urgency as soon as CR1 is achieved in this subset of AML patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Future liver remnant volume (FLRV) is a crucial factor impacting resectability of colorectal liver metastases (CLM). In case of low FLRV, augmentation can be done by performing portal vein embolization (PVE). However, there is a risk of progression of CLM between PVE and resection. Intraportal application of autologous hematopoietic stem cells (HSC) is a possibility to accelerate the growth of FLRV. The effect of thus applied SC on CLM progression still remains unclear, though., Methods: 63 patients underwent PVE between 2003 and 2015. In 20 patients a product with HSC was applied intraportally on the first day after PVE (PVE HSC group). HSC were gained from peripheral blood (10 patients) or bone marrow (10 patients). FLRV and volume of liver metastases (VLM) were evaluated by CT volumetry. The gained data were statistically evaluated in relation to the disease free interval (DFI), overall survival (OS), achievement of CLM resectability and progression of extrahepatic metastases. We compared the PVE HSC group with the group of patient undergoing simple PVE., Results: No significant difference in FLRV and VLM growth was observed between the study groups. The percentage of exploratory laparotomies was smaller in the group with PVE and HSC application. Patients with simple PVE had a significantly higher incidence of extrahepatic metastases during follow up. We did not observe any significant differences in DFI and OS between the groups., Conclusion: HSC application did not accelerate CLM growth in comparison with PVE alone. PVE and HSC application had a higher percentage of patients undergoing liver resection and a lower incidence of extrahepatic metastases.

Background: Allogeneic hematopoietic stem cell transplantation is one of the therapeutic options for patients with relapsed or refractory classic Hodgkins lymphoma (cHL). In the case of dis-ease relapse after transplant, other treatment options are still limited (for example donor lymphocyte infusion, and chemother-apy with brentuximab, bendamustine, or other agents) with uncertain outcomes in terms of patient tolerance and long-term dis-ease remission. One way to achieve remission is administration of the PD-1 inhibitor nivolumab, a PD-1 checkpoint inhibitor. Nivolumab is also indicated for the treatment of cHL relapses after autologous hematopoietic stem cell transplantation. Since September 2018, nivolumab has been approved by the State Institute for Drug Control in the Czech Republic for treatment of cHL autologous hematopoietic stem cell transplantation relapse; however, treatment with nivolumab is accompanied by an increased risk of develop-ing fatal, acute graft-versus-host dis-ease., Case: The article describes the development of resistant acute graft-versus-host disease in a patient who had received allogeneic-unrelated transplantation and nivolumab treatment for Hodgkins lymphoma relapse., Conclusion: Our case study, as well as the literature review, demonstrates the excellent efficacy of PD-1 inhibitors, but also cautions against the administration of these agents in patients follow-ing allogeneic hematopoietic stem cell transplantation. Administration of nivolumab to these patients should be done on a strictly individual basis in the context of known risks, and consideration should be given to other treatment options. Key words Hodgkins lymphoma -&#8202; PD-1 inhibitor -&#8202; nivolumab -&#8202; GvHD -&#8202; transplantation.

Hemophagocytic lymfohistiocytosis (HLH) is rare, life-threatening condition, characterized by excessive activation of immune system with subsequent proinflammatory state resulting in multiorgan failure. Most frequently, it appears in infancy as a primary disorder caused by mutation of immune-regulatory genes. Increasingly, HLH is being diagnosed as a secondary - adult - form, which occurs as a result of aberrant immune response. Viral or bacterial systemic infections, malignancy with a predominance of lymphoproliferative disorders and autoimmune diseases are the most common triggers. Early diagnosis and initiation of therapy is crucial and increase the chance for recovery. HLH is usually presented as multisystem febrile illness, where an extensive differential diagnosis is needed. Diagnosis of HLH is defined by a combination of clinical and laboratory findings, eventually by a proof of specific mutation. The basic mechanism of therapy is an interruption of aberrant immune response by destruction and suppression of T-lymphocytes function. This is mostly achieved by corticosteroid and etoposide therapy. This review summarizes pathophysiology, diagnostics and therapy of HLH. Furthermore, a case-report of 22-years old patient with secondary HLH being manifested predominantly with acute respiratory failure is presented.Key words: acute respiratory failure - hemophagocytic lymphohistiocytosis - HLH-94 - macrophage activation syndrome - MODS.

Objectives: This study aimed to evaluate the progress of future liver remnant volume (FLRV) in patients with liver metastases after portal vein embolization (PVE) with the application of hematopoietic stem cells (HSCs) and compare it with a patients control group after PVE only., Methods: Twenty patients (group 1) underwent PVE with contralateral HSC application. Subsequently, CT volumetry with the determination of FLRV was performed at weekly intervals, in total three weeks. A sample of twenty patients (group 2) who underwent PVE without HSC application was used as a control group., Results: The mean of FLRV increased by 173.2 mL during three weeks after the PVE/HSC procedure, whereas by 98.9 mL after PVE only (p = 0.015). Furthermore, the mean daily growth of FLRV by 7.6 mL in group 1 was significantly higher in comparison with 4.1 mL in group 2 (p = 0.007)., Conclusions: PVE with the application of HSC significantly facilitates growth of FLRV in comparison with PVE only. This method could be one of the new suitable approaches to increase the resectability of liver tumours.

Icodextrin peritoneal dialysis (PD) solution has been shown to increase interleukin-6 (IL-6) levels in PD effluent as well as leukocyte and mesothelial cell count. Mesothelial cells release cancer antigen 125 (CA125), which is used as a marker of mesothelial cell mass. This 1-year prospective study was designed to compare peritoneal effluent cell population, its inflammatory phenotype and biocompatibility biomarkers IL-6 and CA125 between icodextrin (E) and glucose bicarbonate/lactate (P) based PD solutions. Using baseline peritoneal ultrafiltration capacity, 19 stable incident PD patients were allocated either to P only (N = 8) or to P plus E for the overnight dwell (N = 11). Flow cytometry was used to measure white blood cell count and differential and the expression of inflammatory molecules on peritoneal cells isolated from timed overnight peritoneal effluents. Compared to P, E effluent showed higher leukocyte (10.9 vs. 7.9), macrophages (6.1 vs. 2.5) and mesothelial cells (0.3 vs. 0.1)×10(6) /L count, as well as expression of HLA DR on mesothelial cells and IL-6 (320.5 vs. 141.2 pg/min) on mesothelial cells and CA125 appearance rate (159.6 vs. 84.3 IU/min), all P < 0.05. In the E group, correlation between IL-6 and CA125 effluent levels (r = 0.503, P < 0.05) as well as appearance rates (r = 0.774, P < 0.001) was demonstrated. No effect on systemic inflammatory markers or peritoneal permeability was found. Icodextrin PD solution activates local inflammation without systemic consequences so the clinical relevance of this observation remains obscure. Correlation between effluent IL-6 and CA125 suggests that CA125 might be upregulated due to inflammation and thus is not a reliable marker of mesothelial cell mass and/or biocompatibility., (© 2016 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Cell therapy products represent a new trend of treatment in the field of immunotherapy and regenerative medicine. Their biological nature and multistep preparation procedure require the application of complex release criteria and quality control. Microbial contamination of cell therapy products is a potential source of morbidity in recipients. The automated blood culture systems are widely used for the detection of microorganisms in cell therapy products. However the standard 2-week cultivation period is too long for some cell-based treatments and alternative methods have to be devised. We tried to verify whether a shortened cultivation of the supernatant from the mesenchymal stem cell (MSC) culture obtained 2 days before the cell harvest could sufficiently detect microbial growth and allow the release of MSC for clinical application. We compared the standard Ph. Eur. cultivation method and the automated blood culture system BACTEC (Becton Dickinson). The time to detection (TTD) and the detection limit were analyzed for three bacterial and two fungal strains. The Staphylococcus aureus and Pseudomonas aeruginosa were recognized within 24 h with both methods (detection limit ~10 CFU). The time required for the detection of Bacillus subtilis was shorter with the automated method (TTD 10.3 vs. 60 h for 10-100 CFU). The BACTEC system reached significantly shorter times to the detection of Candida albicans and Aspergillus brasiliensis growth compared to the classical method (15.5 vs. 48 and 31.5 vs. 48 h, respectively; 10-100 CFU). The positivity was demonstrated within 48 h in all bottles, regardless of the size of the inoculum. This study validated the automated cultivation system as a method able to detect all tested microorganisms within a 48-h period with a detection limit of ~10 CFU. Only in case of B. subtilis, the lowest inoculum (~10 CFU) was not recognized. The 2-day cultivation technique is then capable of confirming the microbiological safety of MSC and allows their timely release for clinical application.

Mesenchymal stromal cells (MSC) represent a promising treatment of graft-versus-host disease (GVHD) in patients after allogeneic haematopoietic stem cell transplantation. We performed co-cultivation experiments with non-specifically stimulated lymphocytes to characterize the immunosuppressive activity of MSC. MSC influenced expression of some activation antigens. CD25 expression was lower with MSC and reached 55.2 % vs. 84.9 % (CD4+, P = 0.0006) and 38.8 % vs. 86.6 % (CD8+, P = 0.0003) on day +4. Conversely, CD69 antigen expression remained higher with MSC (73.3 % vs. 56.8 %, P = 0.0009; 59.5 % vs. 49.7 %, ns) and its down-regulation along with the culture time was less pronounced. MSC reduced proliferation of the stimulated lymphocytes. The cell percentages detected in daughter generations were decreased (32.82 % vs. 10.68 % in generation 4, P = 0.0004 and 29.85 % vs. 10.09 % in generation 5, P = 0.0008), resulting in a lower proliferation index with MSC (1.84 vs. 3.65, P < 0.0001). The addition of MSC affected expression of some cytokines. Production of pro-inflammatory cytokines was decreased: IL-6 (19.5 vs. 16.3 MFI; P < 0.0001 in CD3+/CD4+ and 14.5 vs. 13.2 MFI; P = 0.0128 in CD3+/CD8+), IFN-γ (13.5 vs. 12.0 MFI; P = 0.0096 in CD3+/CD4+). Expression of anti-inflammatory IL-10 was only slightly increased after the addition of MSC (ns). The analysis confirmed the immunomodulatory activity of MSC. The functional tests have proved to be an important part of the quality control of the advanced therapy cellular product intended for GVHD treatment. Future research should focus on the interaction between MSC and the patient immune environment more closely.

Patients with chronic lymphocytic leukemia with deletion of the short arm of chromosome 17 (17p -) or mutation of the TP53 gene have significantly worse prognosis with a higher risk of progression to symptomatic disease, worse and shorter responses to chemo immunotherapy, and more frequent occurrence of Richters syndrome. TP53 deletion/ mutation is currently the only genetic abnormality that independently predicts response to treatment and also affects the choice of therapeutic approach in chronic lymphocytic leukemia. This work summarizes treatment options available for this poor prognosis variant of chronic lymphocytic leukemia. Traditional chemo immunotherapy (e. g. FCR) does not offer longterm disease control, and patients with TP53 deletion/ mutation were usually considered to undergo allogeneic bone marrow transplantation. New molecules from the group of BCR inhibitors or BCL2 antagonists achieve excellent efficacy in chronic lymphocytic leukemia with del17p even in relapsed/ refractory (R/ R) cases, with a higher percentage of responses and prolonged survival without progression. Clinical trials are ongoing to determine optimal therapeutic approach and to induce longterm remission of the disease. The new molecules change algorithms for treatment of patients with TP53 aberration, including indication for allogeneic transplantation. Especially younger patients should be consulted in centers of intensive hematological care to consider their inclusion into clinical trials testing new molecules or to indicate allogeneic transplantation at the optimal time.

Peripheral blood stem cells (PBSCs) are preferred source of hematopoietic stem cells for autologous transplantation. Mobilization of PBSCs using chemotherapy and/or granulocyte colony-stimulating factor (G-CSF) however fails in around 20%. Combining G-CSF with plerixafor increases the mobilizations success. We compared cost-effectiveness of following schemes: the use of plerixafor "on demand" (POD) during the first mobilization in all patients with inadequate response, the remobilization with plerixafor following failure of the first standard mobilization (SSP), and the standard (re)mobilization scheme without plerixafor (SSNP). Decision tree models populated with data from a first-of-a-kind patient registry in six Czech centers (n = 93) were built to compare clinical benefits and direct costs from the payer's perspective. The success rates and costs for POD, SSP and SSNP mobilizations were; 94.9%, $7,197; 94.7%, $8,049; 84.7%, $5,991, respectively. The direct cost per successfully treated patient was $7,586, $8,501, and $7,077, respectively. The cost of re-mobilization of a poor mobilizer was $5,808 with G-CSF only and $16,755 if plerixafor was added. The total cost of plerixafor "on-demand" in the sub-cohort of poor mobilizers was $17,120. Generally, plerixafor improves the mobilization success by 10% and allows an additional patient to be successfully mobilized for incremental $11,803. Plerixafor is better and cheaper if used "on demand" than within a subsequent remobilization., (Copyright © 2013 Wiley Periodicals, Inc.)