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Chimeric antigen receptor (CAR) T cell therapy has been gradually building its position in the treatment of hematological malignancies. Currently, there are three types of autologous anti-CD19 CAR-T cells approved for the treatment of selected relapsed B cell non-Hodgkins lymphomas and acute B-lymphoblastic leukemia in the Czech Republic. Additional clinical trials are ongoing to evaluate CAR-T cell therapy that targets other tumor-specific antigens. It is expected that some of these CAR-T cells will be approved for the treatment of other hemato-oncological dia-gnoses in the near future. Manufacturing and management of CAR-T cell therapy have been optimized. European Society for Blood and Marrow Transplantation and American Society for Transplantation and Cellular Therapy have updated their recommendations for the management and treatment of early CAR-T cell toxicity based on valuable experience gained during several years. Nevertheless, late toxicity remains an issue. It is crucial for patients undergoing this highly specific therapy to stay in follow-up for several decades. Intensive research and development have been devoted to manufacturing new CAR constructs with higher efficacy and lesser toxicity. A significant improvement in the availability of this, otherwise very expensive treatment, is expected from universal allogeneic T cells that will express CAR binding to tumor-specific antigen.This review is focused on the preparation and administration of autologous CAR-T lymphocytes.

Introduction: One of the hallmarks of cancerogenesis is the ability of tumor cells to evade the immune system. They can achieve it by abusing inhibitory immune checkpoint pathways, which, under normal circumstances, maintain peripheral tolerance during infection. Immune checkpoint inhibitors, especially anti-PD-1/PD-L1 monoclonal antibodies, currently represent a widely discussed treatment option not only in solid oncology, but in hematology-oncology as well.Areas covered: The manuscript is focused on clinical research concerning PD-1/PD-L1 blockade in lymphoma and multiple myeloma in order to identify the patients who would profit the most from this treatment modality. The authors reviewed articles on the topic on PubMed and relevant clinical trials on clinicaltrials.gov before October 2019.Expert opinion: So far, nivolumab and pembrolizumab have been approved for treating patients with relapsed/refractory classical Hodgkin lymphoma and primary mediastinal B cell lymphoma. Nevertheless, monotherapy alone is not curative and a combinational approach is needed. Modern treatment strategies and combinations are comprehensively summarized in this manuscript. There is no approved immune checkpoint inhibitor for the multiple myeloma indication. Although the combination of PD-1/PD-L1 inhibitors with immunomodulatory agents initially seemed promising, unexpected immune related toxicities have stopped any further development. Novel strategies and more potent combinations in myeloma and lymphoma are further discussed in the manuscript.

The diagnosis of Waldenström’s macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, can be challenging due to the different forms of disease presentation. Furthermore, in recent years, WM has witnessed remarkable progress on the diagnostic front, as well as a deeper understanding of the disease biology, which has affected clinical practice. This, together with the increasing variety of tools and techniques available, makes it necessary to have a practical guidance for clinicians to perform the initial evaluation of patients with WM. In this paper, we present the consensus recommendations and laboratory requirements for the diagnosis of WM developed by the European Consortium of Waldenström’s Macroglobulinemia (ECWM), for both clinical practice as well as the research/academical setting. We provide the procedures for multiparametric flow cytometry, fluorescence in situ hybridization and molecular tests and with this offer guidance for a standardized diagnostic work-up and methodological workflow of patients with IgM monoclonal gammopathy of uncertain significance, asymptomatic and symptomatic WM.

For patients with indolent non-Hodgkin lymphoma who fail initial anti-CD20–based immunochemotherapy or develop relapsed or refractory disease, there remains a significant unmet clinical need for new therapeutic approaches to improve outcomes and quality of life. 177Lu-lilotomab satetraxetan is a next-generation single-dose CD37-directed radioimmunotherapy (RIT) which was investigated in a phase 1/2a study in 74 patients with relapsed/refractory indolent non-Hodgkin B-cell lymphoma, including 57 patients with follicular lymphoma (FL). To improve targeting of 177Lu-lilotomab satetraxetan to tumor tissue and decrease hematologic toxicity, its administration was preceded by the anti-CD20 monoclonal antibody rituximab and the “cold” anti-CD37 antibody lilotomab. The most common adverse events (AEs) were reversible grade 3/4 neutropenia (31.6%) and thrombocytopenia (26.3%) with neutrophil and platelet count nadirs 5 to 7 weeks after RIT. The most frequent nonhematologic AE was grade 1/2 nausea (15.8%). With a single administration, the overall response rate was 61% (65% in patients with FL), including 30% complete responses. For FL with ≥2 prior therapies (n = 37), the overall response rate was 70%, including 32% complete responses. For patients with rituximab-refractory FL ≥2 prior therapies (n = 21), the overall response rate was 67%, and the complete response rate was 24%. The overall median duration of response was 13.6 months (32.0 months for patients with a complete response). 177Lu-lilotomab satetraxetan may provide a valuable alternative treatment approach in relapsed/refractory non-Hodgkin lymphoma, particularly in patients with comorbidities unsuitable for more intensive approaches. This trial was registered at www.clinicaltrials.gov as #NCT01796171.

Poznani funkce B-buněcneho receptoru a jeho signalizacni kaskady umožnilo vývoj molekul, ktere inhibuji jednotlive enzymy teto drahy. Ibrutinib je inhibitor Brutonovy tyrozinkinazy, ktera ma klicove postaveni v přenosu signalu tohoto receptoru. V soucasne době je preparat registrovaný pro lecbu relabujici a refrakterni B-chronicke lymfocytarni leukemie, primoterapii B-chronicke lymfocytarni leukemie s průkazem delece kratkeho ramenka chromozomu 17 nebo mutace genu TP53, lecbu relapsu lymfomu z plasťových buněk a dale pro lecbu nově lecene a relabujici Waldenstromovy makroglobulinemie. V praci je bliže popsan mechanizmus ucinku a výsledky klinických studii hodnotici efektivitu a bezpecnost tohoto preparatu.

Cyclophosphamide (Cy) plus granulocyte-colony stimulating factor (G-CSF) is currently a standard regimen for hematopoietic stem cell (HSC) mobilization in patients with multiple myeloma (MM). However, cytarabine (AraC) in intermediate doses plus G-CSF seems to have a higher mobilization efficacy. The aim of this study was to retrospectively compare mobilization using AraC and Cy. Thirty consecutive MM patients were mobilized by Cy + G-CSF, and the subsequent 40 patients by AraC + G-CSF. Both groups were comparable. The target yield of 10 × 106 CD34+ cells/kg (for tandem and 2 additional transplantations) was achieved in 98% (AraC) and 57% (Cy) of patients (p

Waldenstrom's macroglobulinemia (WM) is a complex disease characterized by apparent morphological heterogeneity within the malignant clonal cells representing a continuum of small lymphocytes, plasmacytoid lymphocytes, and plasma cells. At the molecular level, the neoplastic B cell-derived clone has undergone somatic hypermutation, but not isotype switching, and retains the capability of plasmacytic differentiation. Although by classical definition, WM is formed by monoclonal expansion, long-lived clonal B lymphocytes are of heterogeneous origin. Even more, according to current opinion, plasma cells also conform certain population with pathogenic and clinical significance. In this article, we review the recent advances in the WM clonal architecture, briefly describe B-cell development during which the molecular changes lead to the malignant transformation and mainly focus on differences between two principal B-lineage clones, including analysis of their genome and transcriptome profiles, as well as immunophenotype features. We assume that the correct identification of a number of specific immunophenotypic molecular and expression alterations leading to proper aberrant clone detection can help to guide patient monitoring throughout treatment and successfully implement therapy strategies directed against both B- and plasma cell tumor WM clones.

The introduction of PD-1/PD-L1 pathway inhibitors is an important landmark in solid oncology with unprecedented practice-changing activity in various types of solid tumours. Among haematological malignancies, PD-1/PD-L1 inhibitors have been successful, so far, only in the treatment of classical Hodgkin lymphoma, which typically exhibits an over-expression of PD-1 ligands (PD-L1, PD-L2) due to alterations in chromosome 9p24.1. Such positive outcomes led to the US Food and Drug Administration approval of nivolumab use in relapsed Hodgkin lymphoma in 2016 as the first haematological indication. Although the results in other lymphoid malignancies have not been so striking, blockade of the PD-1/PD-L1 axis has led to meaningful responses in other lymphoma types such as diffuse large B-cell lymphoma, follicular lymphoma or several T-cell lymphomas. Monotherapy with PD-1/PD-L1 inhibitors in chronic lymphocytic leukaemia and multiple myeloma has been unsatisfactory, suggesting that a combinational approach with other synergistic drugs is needed. In the case of multiple myeloma, immunomodulatory agents together with corticosteroids represent the most promising combinations. Among myeloid malignancies, the anti-PD-1 monoclonal antibodies are examined dominantly in acute myeloid leukaemia and myelodysplastic syndromes in combination with potentially synergistic hypomethylating drugs such as 5-azacitidine, resulting in promising outcomes that warrant further investigation. We have described all available clinical results of PD-1/PD-L1 inhibitors in haematological malignancies and discussed related toxicities, as well as highlighted crucial preclinical studies in this review.

Waldenströms macroglobulinemia (WM) is a B-cell malignancy characterized by high level of monoclonal immunoglobulin M (IgM) paraprotein in blood serum and associated with the bone marrow infiltration by malignant cells with lymphoplasmacytic differentiation. WM remains incurable advances in therapy. Most of WM cases are associated with a somatic point mutation L265P in MYD88. Significantly higher risk of progression from the IgM monoclonal gammopathy of undetermined significance (IgM MGUS) to WM for patients with mutated MYD88 gene suggests that this mutation is an early oncogenic event and plays a central role in development of malignant clones. The second, most prevalent mutation in WM is found in the CXCR4 gene and is often associated with drug resistance and aggressive disease presentation. Therefore, detection of these mutations (MYD88L265P and CXCR4S338X) could be useful diagnostic and prognostic tool for the patients with WM. While detection of these mutations in bone marrow sample is common, the aim of our study was to compare sensitivity of detection of mutation from different cell fraction from peripheral blood and bone marrow. The results show possibility to describe MYD88 and CXCR4 mutation status even from peripheral blood sample (sensitivity for MYD88L265P was 100%, for CXCR4S338X 91%), which significantly facilitate material collection. Moreover, comparable detection sensitivity of these mutations in bone marrow and peripheral blood samples examined before and during the therapy offers a promising tool for more routine diagnostic and monitoring of disease progression.Key words: Waldenström macroglobulinemia - hematology - neoplasms - lymphoma - mutation - MYD88 - CXCR4.

Clanok vysvetľuje význam pojmu „bibliomantia“, ktorý oznacuje historicku praktiku využivania knih na „vestecke“ ucely. Uvedený postup pozostava spravidla zo zamerne nahodneho výberu casti textu a jeho zamerne subjektivnej interpretacie vo vzťahu k aktualnej potrebe použivateľa. U použivateľa tak dochadza k objaveniu osobne relevantneho významu aj v obsahovo nerelevantných informaciach ci informacných zdrojoch. V nadvaznosti na bibliomantiu je navrhnutý nový pojem „infomantia“, ktorý možnosť iracionalneho pristupu k verbalnym posolstvam už neviaže len na „knihy“ ale otvara ju vo vzťahu k informaciam ako takým, a ktorý zaroveň ako výstup nepredpoklada len predpovedanie buducnosti, ale akukoľvek osobne zmysluplnu subjektivnu interpertaciu. V clanku sa uvadzaju priklady infomantie z dejin i z beletrie. Okrem uplnej infomantie sa rozlisuje i viacero druhov parcialnej infomantie, pri ktorej urcite casti infomantickeho procesu nemusia byť zamerne alebo sa nemusia vobec realizovať, cim sa už ukazuje možnosť prostrednictvom tohto pojmu vysvetliť i bežnejsie skusenosti použivateľov s informaciami. Pojem infomantie sa vďaka svojej komplexnosti može stať užitocným nastrojom na popis jednoduchsich informacných fenomenov a na znazornenie vzťahov medzi nimi. "Paranormal" use of information resources - its variations and perspectives in information society The article explains the concept of "bibliomancy" which denotes ancient practice of using books for divination. This practice usually consists of intentional random selection of text and its intentional subjective interpretation with regards to particular users need. It can be seen as a way of deriving personally relevant meaning even from irrelevant information content. With regards to bibliomancy the article suggests more universal concept of "infomancy" where the possibility of irrational perception and interpretation is not limited to just books (but can be applied to any confronted information) and where the outcome of such interpretation is not limited to just "fortune-telling" (but it can be any kind of personally meaningful "content"). Various cases of infomancy both from history and fiction are mentioned, while the distinction between infomancy and better known information phenomena is made clear. Besides "full" infomancy various "partial" kinds of infomancy can be distinguished, where certain parts of infomantic practice are either unintentional or they are entirely missing, which also shows the possibility of using the concept of infomancy to describe more common information experience. Concept of infomancy is potentially useful tool for description, analysys and comparision of more simple information phenomenons. Michal Kascak Knihovna Waltera Hoopera V Bratislavě