The journal Transfuze a hematologie dnes (Transfusion and Haematology Today) is the official medium of the Society for Transfusion Medicine, the Czech Society of Haematology, and the Czech Society for Thrombosis and Haemostasis of the Czech Medical Society of J. E. Purkyně. Publisher of the journal is the Czech Medical Society of JE Purkyně. Issuer is the company Care Comm. Issues published so far and information about the journal can be found at the following address (after free registration): https://www.prolekare.cz/casopisy/transfuze-hematologie-dnes
Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma and the Real-World Data Perspective
Management of relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) has undergone significant transformation in recent years. Second-line therapy has shifted from conventional salvage regimens toward immunotherapy-based approaches. CAR T-cell therapy is now the preferred option for patients with early relapse or primary refractory disease, while salvage chemoimmunotherapy followed by autologous stem cell transplantation consolidation remains reserved for younger, fit individuals with late relapses. Bispecific antibodies (BiAbs) combined with chemotherapy (i.e., glofitamab plus GemOx) could be effective alternatives for transplant-ineligible patients. Additional novel options include Pola-BR and tafasitamab-lenalidomide, particularly for elderly or frail individuals. In third-line and later settings, treatment is increasingly individualized. CAR T-cell therapy remains the preferred modality if not previously administered; otherwise, BiAbs (glofitamab, epcoritamab, odronextamab), antibody-drug conjugates (loncastuximab tesirine, brentuximab vedotin), and lenalidomide-based regimens are considered. Real-world data from the NiHiL registry support the clinical utility of these novel agents and demonstrate improved survival outcomes following their integration into routine clinical practice.
Copyright (c) 2025 Transfuze a hematologie dnes
Folikulární lymfom: proměna léčebného paradigmatu směrem k chemo-free přístupům
Léčba folikulárního lymfomu (FL) se v posledních letech významně mění směrem k biologicky cíleným, chemo‑free přístupům. U pacientů s nízkou nádorovou náloží zůstává standardem sledování („watch‑and‑wait“) nebo monoterapie rituximabem, zatímco symptomatické onemocnění vyžaduje imunochemoterapii (nejčastěji bendamustin-rituximab, R‑CHOP, obinutuzumab‑bendamustin). U nemocných s relabovaným onemocněním se uplatňují režimy založené na protilátkách (rituximab‑lenalidomid (R²), tafasitamab‑R²), malé molekuly (zanubrutinib‑obinutuzumab) a epigenetická léčba (tazemetostat). Nové na T‑lymfocytech založené terapie – bispecifické protilátky (mosunetuzumab, epcoritamab, odronextamab) a CAR‑T buňky (axi‑cel, tisa‑cel, liso‑cel) – dosahují léčebných úspěchů i u vysoce předléčených nemocných. Moderní monitorovací metody, zejména PET/CT a ctDNA, umožňují přesnější hodnocení léčebné odpovědi a otevírají cestu k individualizované terapii. Trendem je časově omezená, méně toxická léčba s cílem dosažení dlouhodobé remise („funkčního vyléčení“) při zachování kvality života.
folikulární lymfom, imunochemoterapie, bispecifické protilátky, buněčná terapie, funkční vyléčení
Dopis redakci - prosím bez abstraktu.
Early Isolated Central Nervous System Relapse of Mantle Cell Lymphoma Successfully Treated with Ibrutinib and Chimeric Antigen Receptor T-Cell Therapy – A Case Report
Mantle cell lymphoma (MCL) is a relatively rare and clinically distinct subtype of non-Hodgkin lymphoma. Involvement of the central nervous system is an uncommon manifestation at both diagnosis and recurrence. Central nervous system (CNS) relapse more frequently occurs in the context of aggressive disease behavior and portends a poor prognosis. However, advances in therapeutic strategies for MCL have opened the possibility of achieving durable remission, even in this high-risk presentation. We report a case of a patient who developed an early, isolated CNS relapse following autologous stem cell transplantation. The patient was successfully treated with a sequential treatment protocol combining chemoimmunotherapy, ibrutinib and chimeric antigen receptor T-cell therapy.
Treatment of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the Czech Republic in 2025
Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous group of diseases within the category of non-Hodgkin lymphomas, generally associated with a relatively good prognosis. First-line treatment cures approximately 60% of patients. About 40% of patients, however, experience relapse or have primary refractory disease. The prognosis for these patients was historically very poor. In the treatment of relapsed/refractory DLBCL, the timing of first-line treatment failure is currently a key factor. If the failure occurs within 12 months after completion of first-line therapy and the patient is eligible for CAR-T therapy, axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel) should be administered. If the relapse occurs after more than 12 months and the patient is suitable for high-dose therapy, salvage immunochemotherapy followed by autologous stem cell transplantation is indicated. If the patient is not eligible for such high-dose therapy, immunochemotherapy remains the standard second-line treatment. In third and later lines of therapy, more treatment options are now available. These include the bispecific antibody glofitamab. If the patient has not previously received CAR-T therapy, CAR-T treatment is also an option. In cases where these treatment modalities fail, loncastuximab tesirine is available in the Czech Republic for third and later lines of therapy. Other treatment options include the bispecific antibody epcoritamab, the combination of tafasitamab + lenalidomide, or the Pola-BR regimen. However, these treatments are not currently reimbursed, and approval must be requested from the relevant health insurance company under Paragraph 16. A very promising approach is the combination of glofitamab with the GEMOx regimen for second and later lines, based on data from the STARGLO clinical trial. However, this treatment is also not yet reimbursed in the Czech Republic. Looking ahead, it is expected that these new treatment modalities will shift into earlier lines of therapy, but results from ongoing clinical trials must be awaited. Nonetheless, it can be stated that the prognosis for patients with relapsed/refractory DLBCL has significantly improved in recent years.
lymphoma, relapse, DLBCL, CAR-T, axi-cel, liso-cel, bispecific antibodies, glofitamab, prognosis
Guidelines for the management of adverse events following CD19 CAR-T cell therapy in adult patients with lymphomas and acute lymphoblastic leukemia: consensus of expert panel from certified centers in Czechia and Slovakia for 2025
Autologous chimeric antigen receptor T-cells (CAR-T cells) have become a standard of care for hematological malignancies, particularly non-Hodgkin B-cell lymphomas and acute B-lymphoblastic leukemia. An expert panel from all certified centers in Czechia and Slovakia presents these guidelines for the grading, prophylaxis and treatment of common adverse events. These include cytokine release syndrome, neurotoxicity syndrome, hematological toxicity, infections, and other less frequent but specific toxicities. These guidelines are adapted to the local state-of-the-art and are supplemented with concise summary tables designed for use in daily clinical practice.
Generační změna terapie klasického Hodgkinova lymfomu
Klasický Hodgkinův lymfom (cHL) je v moderní hematoonkologii často vnímán jako příběh úspěchu, a to zejména u pacientů mladších 60 let, kde současné léčebné postupy umožňují vyléčení u přibližně 80-90 % nemocných v závislosti na klinickém stadiu. Tento pokrok je výsledkem dlouhodobého výzkumu a zavedení účinných kombinací chemoterapie a radioterapie. Za touto statistikou se však skrývají významné výzvy: akutní i pozdní toxicita standardní léčby a omezené možnosti efektivní terapie pro starší pacienty či nemocné s relabujícím/refrakterním (R/R) průběhem. Klasický HL tak zůstává dynamickým polem vývoje, kde hledání rovnováhy mezi účinností a tolerancí léčby pokračuje. V posledních letech jsme svědky zásadní generační změny v terapeutickém přístupu k léčbě tohoto typu lymfomu, která je poháněna rozvojem cílené léčby a imunoterapie. Nové léky, jako je imunokonjugát (brentuximab vedotin) a inhibitory kontrolních bodů imunity (tzv. immune checkpoint inhibitory - nivolumab, pembrolizumab), změnily léčebné paradigma zejména ve 3. a vyšší linii léčby a postupně v současné době nacházejí nově své místo i v 1. a 2. linii. Tento posun přináší nejen nové možnosti pro zvýšení účinnosti terapie především u starších nemocných a u R/R formy nemoci, ale také potenciál pro snížení toxicity a zlepšení kvality života mladších pacientů. Cílem tohoto sdělení je shrnout současné poznatky o implementaci inovativních přístupů do 1. a 2. linie léčby cHL a diskutovat jejich dopad na klinickou praxi v kontextu měnícího se terapeutického paradigmatu v rámci moderní personalizované medicíny v českých podmínkách.
CAR-T lymphocytes have become an integral part of the treatment arsenal for hematological malignancies, including B-non-Hodgkin's lymphomas (B-NHL). Currently, we have four registered anti-CD19 products available for the treatment of B-NHL. For the treatment of large B-cell lymphomas (LBCL) and follicular lymphoma (FL), axi-cel, liso-cel, and tisa-cel are available, while brexu-cel is registered for the treatment of mantle cell lymphoma (MCL). Registered indications are mostly for the treatment of 3rd and subsequent lines, but for LBCL we can use axi-cel and liso-cel already in the second line. The presented work addresses: 1. general selection of suitable patients in terms of age and comorbidities, 2. pre-treatment examinations, 3. estimating the risks of adverse effects, 4. the adverse effects, 5. expected outcomes, 6. decision-making algorithms or elements of decision-making algorithms for each malignancy. In the chapter about LBCL, case report is included. The main aim of the work is to assist clinicians who first diagnose relapsed patients and decide on their referral to specialized centers.
Modern therapeutic approaches in the treatment of relapsed and refractory marginal zone lymphoma
Marginal zone lymphomas (MZL) are a group of indolent B-cell lymphomas originating from B-lymphocytes of the marginal zone of lymphoid follicles of lymph nodes, spleen, or extranodal tissues. The group includes five distinct clinical entities, which together represent the third most common group of non-Hodgkin lymphomas in Czech Republic. In recent years, there has been a significant broadening of treatment options beyond conventional immunochemotherapy for relapsed refractory (R/R) disease. In the MAGNIFY Phase IIIb multicenter study, the combination of lenalidomide and rituximab followed by rituximab maintenance therapy in 76 patients with R/R MZL after failure of ≥ 1 prior line of therapy.achieved an overall response rate (ORR) of 64 % (49/76), complete remission (CR) in 39 % (30/76), and a median progression-free survival (PFS) of 41.2 months. Bruton's tyrosine kinase inhibitors, particularly zanubrutinib, have significantly expanded the treatment options for R/R disease. In the MAGNOLIA phase II, zanubrutinib led to an ORR of 68.2 % (45/66) and CR of 25.8 % (17/66) in patients who had received at least one prior line of anti-CD20 therapy. The two-year estimated PFS) was 70.9 %, and the toxicity profile was favorable. Therapy with T lymphocytes with chimeric antigen receptors also appears highly promising, particularly the liso-cel, which achieved an ORR of 95.5 % (63/66), a CR of 62.1 % (41/66) and an estimated 2year PFS of 85.7 % in R/R patients with a median of 3 previous lines of treatment in the TRANSCEND FL trial. Data on the efficacy and safety of bispecific antibodies in MZL is currently limited, with relatively the most information available on odronextamab. In the phase II ELM-2 trial, odronextamab monotherapy led to an ORR and CR of 79.3 % (23/29) in patients after ≥ 2 lines of systemic therapy.
Moderní strategie léčby CLL: význam fixních režimů a jejich opětovného využití
The introduction of fixed-duration treatment regimens represents a significant advancement in managing chronic lymphocytic leukemia (CLL), as it allows the achievement of deep remissions without the need for continuous medication. Combinations of targeted agents—particularly venetoclax with obinutuzumab or a Bruton tyrosine kinase inhibitor—have demonstrated high efficacy and a favorable safety profile while offering patients the benefit of so-called "treatment holidays." This approach is not only clinically effective but also cost-efficient. An increasingly discussed topic is the potential for re-administration of these regimens in the event of relapse—so-called retreatment. Data from the Murano study and real-world experience suggest that retreatment with venetoclax-based regimens may be effective and well tolerated in selected patients, mainly when relapse occurs after a prolonged treatment-free period. This strategy is already reflected in both Czech and international clinical guidelines, which consider retreatment a reasonable option for patients whose initial response lasted at least 1–2 years. In summary, fixed-duration regimens represent a practical, modern approach to CLL therapy, and the possibility of their repeated use opens new perspectives for sequential treatment strategies in clinical practice. However, as current evidence is derived mainly from retrospective analyses and small patient cohorts, prospective studies with well-defined criteria and long-term follow-up are essential to confirm this approach's efficacy and safety definitively.
Spontánní remise u akutní myeloidní leukémie
SUMMARY Acute Myeloid Leukaemia (AML) is a malignant hematopoietic disorder with high mortality, which remains challenging to treat despite advances in therapy, particularly in older patients with comorbidities and those at high risk. The vast majority of patients require intensive treatment, and achieving consolidation of remission and cure often necessitates allogeneic hematopoietic stem cell transplantation. Nevertheless, there are extremely rare cases of spontaneous remission of AML, which are typically of short duration. Hypotheses regarding the underlying mechanism of spontaneous remission frequently highlight an immune-mediated effect, often following an infection. This study focuses on a review of available case reports describing instances of spontaneous remission between 2004 and 2023. In total, we identified 27 cases in patients with a median age of 59 years (range 28–77 years), 19 of whom were male. The most common subtypes of AML were M2 and M4, with a normal karyotype being the most frequently reported cytogenetic finding. The duration of spontaneous remission ranged from 0.3 to 120 months, with a median of 6 months. We also briefly describe our own experience with a case of spontaneous remission in a 75year-old woman with a cytogenetic finding of t(9;11)(p21;q23) and trisomy 8, whose spontaneous remission has currently lasted 48 months.
spontaneous remission, acute myeloid leukaemia
Recommendations for chronic lymphocytic leukaemia diagnosis and therapy
The treatment of chronic lymphocytic leukaemia (CLL) has changed dramatically in recent years. New oral signalling pathway targeted inhibitors have significantly improved the prognosis of patients with CLL. Currently, two main groups of small molecules are used, namely Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors. However, the results of new clinical trials directly impacting routine clinical practice are rapidly accumulating. We therefore present updated recommendations for the diagnosis and treatment of CLL, based on a comprehensive analysis of the current literature and following the principles of evidence-based medicine.
MYC gene and its abnormalities with a focus on aggressive B-cell lymphomas
The MYC gene encodes the Myc protein, which is one of the most important transcription factors regulating a wide range of cellular functions, including cell proliferation, differentiation and apoptosis. Deregulation of the MYC gene occurs at various levels and its increased expression is associated with a variety of cancers. Deregulation of the gene through chromosomal rearrangement is typical for B-cell lymphomas and is usually accompanied by a more aggressive nature of the disease with an unfavourable prognosis. B-cell lymphomas with a proven MYC gene rearrangement show high variability in the localization of breakpoints in the 8q24 region. The rearrangement involves various translocation partners, both immunoglobulin (IG) genes and non-immunoglobulin (non-IG) genes. The involvement of IG genes as translocation partners of MYC is considered a negative prognostic factor. Co-occurring aberrations of other oncogenes have a significant impact on the prognosis of patients with MYC gene rearrangements. The presence or absence of MYC, BCL2 and BCL6 gene rearrangements, together with morphological assessment, is the defining criterion for the classification of aggressive B-cell lymphomas according to the 5th revised WHO classification (2022). The most suitable method for detecting rearrangements is fluorescence in situ hybridization (FISH), which can be used both on native material and on tissue sections from paraffin blocks. This review discusses the physiological function of the MYC gene, its deregulation, types of chromosomal aberrations involving MYC gene and their role in cancer pathogenesis with a focus on B-cell lymphomas.
MYC gene, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), high-grade B-lymphoma (HGBL), fluorescence in situ hybridization (FISH)
Automated digital cytomorphology increases the reliability of bone marrow diagnostics
Thrombotic microangiopathies represent a heterogeneous group of diseases of various etiology, whose common feature is damage to the endothelium of small blood vessels. Typical laboratory findings include thrombocytopenia and microangiopathic hemolytic anemia, along with signs of organ damage (most commonly affecting the kidneys). In the differential diagnosis, it is necessary to differentiate, among other things, autoimmune diseases with multi-organ failure. This case report presents the case of a young woman who developed multi-organ failure in the early postpartum period. For this patient, it was the first manifestation of systemic lupus erythematosus. Despite prompt diagnosis and treatment, the course of hospitalization was complicated—both due to the underlying disease and due to severe infections that required adjustments to her immunosuppressive therapy. The patient was discharged to outpatient care after nearly four months of intensive treatment, and her condition continues to improve.
Successful treatment of MDS-IB2 and chronic lymphocytic leukemia with venetoclax - case report
In this case report, we present the case of a 61-year-old female patient with chronic lymphocytic leukemia (CLL) and myelodysplastic syndrome with increased blasts 2 (MDS-IB2). The rare coincidence of these two diseases has made it possible to reaveal the therapeutic potential of venetoclax in patients with high-risk MDS. While venetoclax is a common therapeutic option in the diagnosis of CLL, it is still the subject of clinical trials in the management of MDS treatment. Due to the presumed therapeutic overlap of the mentioned BCL2 inhibitor, it was chosen in the first line for the treatment of CLL in our case report. Although the treatment was initially complicated by severe prolonged pneumonia, after a short duration of venetoclax and azacitidine both diseases were in remission and the patient was able to undergo allogeneic hematopoietic cell transplantation (HSCT). Apart from corticosensitive acute GvHD of the skin and liver, the HSCT was performed without the feared infectious complications. Even 35 months after the HSCT, the complete treatment response with 100% chimerism persists.
Results after first-line treatment of non-Hodgkin and Hodgkin lymphoma treated between 2013 and 2022 in Department of Hematooncology, Faculty Hospital in Ostrava, Czech Republic.
Lymphomas are a heterogenous group of blood malignancies, having different histopathological, immunohistochemical and clinical features, as well as different prognosis and therapy. In our retrospective analysis, we put forward results after 1st line of therapy of 668 patients with non-Hodgkin lymphoma (NHL) and 142 patients with Hodgkin lymphoma (HL) treated between 2013 and 2022 in Department of Hematooncology, Faculty Hospital in Ostrava, Czech Republic. We focus mainly on diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and HL with major interest in overall response rate (ORR), progression free survival (PFS) and overall survival (OS). In the DLBCL group, 82% (221/274) patients received R-CHOP/ R-CHOP-like treatment. The complete remission (CR) rate in this cohort was 80% (177/221), median PFS and OS was 122 months and five-year PFS and OS was 61% and 66%, respectively. Low IPI risk was associated with better PFS and OS, which was also partially true for GCB (Germinal Centre B-cell like) immunophenotype. Of 134 patients with FL, 60% (80/134) received chemotherapy in combination with anti-CD20 monoclonal antibody as 1st line treatment, with 95% ORR (76/80) and 76% CR (62/80). The median PFS and OS was not reached for the whole group. The five-year PFS and OS was 63% and 86%, respectively. Better survival rate was observed in patients with localized Lugano stage at the time of diagnosis and low FLIPI. Of 142 patients with HL, 96% (136/142) had classical HL (cHL). For this group, median PFS and OS was not reached. The five-year PFS and OS was 75% and 86%, respectively. The respective five-year PFS and OS in early stages was 94% and 100%, in intermediate stages 84% and 90%, in advanced stages 68% and 81%. Our observed results of lymphoma patients with standard treatment are comparable to results from clinical trials and other authors’ analyses from daily clinical practice.
difuzní velkobuněčný B-lymfom, folikulární lymfom, Hodgkinův lymfom, celkové přežití, doba do progrese, prognóza
Trends in allogeneic hematopoietic cell transplantations - analysis of the activities of the transplantation center of the University Hospital Pilsen in the period 2001-2021.
Allogeneic hematopoietic cell transplantation (alloHCT) is evolving both in terms of indications and execution. We retrospectively evaluated this evolution in 855 consecutive transplanted patients between 2001 and 2021 by comparing 3 7-year time periods: 2001-2007 (n=257, period/cohort A), 2008-2014 (n=304, period/cohort B) and 2015-2021 (n=294, period/cohort C). There was a significant increase in the median age of patients over the study periods - 50 years (range 20-68) vs. 53 years (19-71) vs. 55 years (20-74), p<0,0001. Similarly, the proportion of patients ≥70 years increased from 0 in A to 23 (8 %) in C, p<0,0001. This reflects a decrease in the use of myeloablative regimens (43 % in period A vs. 24 %/28 % in periods B/C, p<0,0001). Changes in donor type were substantial, with an increase in haploidentical donors in period C: 27 % vs. 1 %/0 % in periods B/A (p<0,0001). Concurrently, the proportion of identical siblings decreased (41 % to 26 % and 9 % respectively, p<0,0001), while the proportion of unrelated donors remained stationary (60 % vs. 73 % vs. 64 %). Bone marrow as a source of hematopoietic cells increased from 11 % to 20 % in period B (p=0,0049), then became stationary (18 %, p=0.943). CNI/MTX as GVHD prophylaxis was the mainstay in all transplant types except haploidentical, where PTCY was used exclusively. However, the use of ATG has increased significantly (from 22 % to a recent 55 %, p<0,0001). In all periods, myeloid malignancies (AML/MDS/MPN) were the main indication, with a steady increase (39 % in period A vs. 62 % in period C, p<0,0001). On the other hand, CML and CLL showed a significant decrease (11 %, 4 % and 1 %, p<0,0001, respectively, 14 %, 13 % and 3 %, p<0,0001). The proportion of other indications - ALL, NHL, MM, MH, MPN - remained essentially the same with non-significant variations between periods (e.g. ALL 9 %, 13 % and 9 %, p=0,1608). The analysis documents a trend to transplant increasingly older patients and a predominance of unrelated or haploidentical transplants. Myeloid malignancies remain the dominant indication, but there has been a significant decline in CML and CLL.
allogeneic hematopoietic stem cell transplantation
Je dlouhodobé podávání interferonů u polycythemia vera spojeno s riziky?
Therapy of myeloproliferative diseases with interferons is experiencing a renaissance, there are basically three reasons. Extending the effect of pegylation. Improvement of local tolerance and limitation of cytokine release by pegylation. New and encouraging evidence of efficacy with solid tolerance for pegylated interferons. Individual pegylated interferons differ from each other both from a chemical point of view and also in the three-dimensional structure of positional isomers, while one of the pegylated interferons – ropeginterferon α2b – is made up of a single molecule and has no positional isomers. Isomers of pegylated interferons appear to have different biological activity. The two largest databases of adverse effects, the American FAERS and the European Eudravigilance, show very homogeneously that there are differences in the incidence and severity of adverse effects between pegylated interferons. In addition, these differences confirm the results of controlled phase 2 and 3 clinical trials, which, among other things, monitored the incidence of premature termination of therapy due to adverse effects. Based on the analysis of adverse effects and the results of controlled clinical trials, it can be stated that ropeginterferon α2b has a significantly better tolerability in the indication of polycythemia vera compared to peginterferon α2a and peginterferon α2b, across virtually all classes of adverse effects according to the MedDRA classification. Additionally, a significantly lower proportion of patients have to discontinue ropeginterferon α2b therapy prematurely due to adverse effects compared to peginterferon α2a or peginterferon α2b therapy. Information about the safety of the therapy is important for the doctor in the same way that the information about the clinical effectiveness is important, because the set of this knowledge will help the doctor to make the optimal choice of the drug for the patient.
ukončení (vysazení) terapie z důvodu nežádoucích účinků
Czech and international advancements in the treatment and research of chronic myeloid leukemia
The article highlights a selection from oral presentations held at hematological conferences in the Czech Republic in September 2024, focusing on the treatment and research of chronic myeloid leukemia.
Myelomem indukované kardiovaskulární problémy
S Summary Cardiovascular complications in multiple myeloma Most patients with multiple myeloma (MM) are over 50 years old, with a median age of diagnosis of 70 years and this is the age when cardiovascular disease is common. In patients with MM, the incidence of hypertension has been shown to be higher than in the average population of the same age, and cardiovascular disease is present in 69% of MM patients. Myeloma cells have some pathophysiological mechanisms negatively affecting the cardiovascular system, and the drugs used also have a negative effect. Myeloma cell products can damage the cardiovascular system by the following mechanisms: damage to the heart by light chain deposits in amyloid or amorphous form, hyperviscosity, hyperkinetic heart failure in shunt circulation, pulmonary hypertension, negative effects of anaemia and renal failure on cardiovascular fitness. It is important for patients that their doctor is familiar with these phenomena and adjusts the treatment of MM appropriately so that the benefits always outweigh the side effects. The review summarizes current knowledge of the pathophysiology of cardiovascular complications in patients with symptomatic MM. Keywords: cardiovascular complications of multiple myeloma.
Kardiovaskulární komplikace, které mohou způsobit protimyelomové léky
Cardiovascular complication of anti-myeloma therapy Most patients with multiple myeloma (MM) are over 50 years old, an age when cardiovascular disease is common. Therefore, it is necessary to be aware of the adverse cardiovascular effects of anti-myeloma drugs. Of the classic cytostatics, doxorubicin has a well-known cardiotonic effect. However, high doses of cyclophosphamide, used for collecting hematopoietic stem cells, can also cause cardiovascular complications. Therefore, in case of heart damage caused by AL-amyloidosis, it is recommended to collect stem cells after G-CSF. Doses of melphalan, which are common in hematopoietic stem transplantation, can also have a negative effect on the heart and induce arrhythmias. Of the group of proteasome inhibitors, carfilzomib has the most cardiovascular adverse reactions, after bortezomib they have been described to a much lesser extent, cardiotoxicity is not described for ixazomib. Drugs from the IMiDs group have a predominant procoagulant effect, requiring targeted prophylaxis of thrombosis and pulmonary embolism, but rhythm disturbances have also been described. Treatment with new anti-CD38 monoclonal antibodies is not associated with evident cardiotoxicity, but cardiovascular side effects are described with glucocorticoids, which are the standard premedication for anti-CD antibodies. The aim of this article is to inform about the incidence of these complications associated with antimyeloma treatment. Keywords: cardiovascular complications of multiple myeloma, cyclophosphamide, melphalan proteasome inhibitors, IMiDs drugs, anti-CD38 monoclonal antibodies
Poškození ledvin monoklonálním imunoglobulinem a / nebo volnými lehkými řetězci. Klasifikace dle „International Kidney and Monoclonal Gammopathy Research Group“.
Summary Monoclonal gammopathy of renal significance (MGRS) was defined in 2012 as etiopathogenetically related kidney damage associated with free light chain (FLC) or monoclonal immunoglobulin (M-Ig). The prevalence of MGRS is described in only two studies. An analysis from the Mayo Clinic showed that 0.8% of people over 50 years of age had light chain MGUS, and 23% of them had kidney damage. Another analysis reported that 10% of people with monoclonal gammopathy who seemed to meet the MGUS criteria suffered some form of damage, corresponding to 0.32% of the population over 50 years of age and 0.53% of those over 70 years of age. Thus, kidney damage from free light chains and/or monoclonal immunoglobulin will be more common than diagnosed. The nomenclature and definition of individual forms of kidney injury within MGRS was developed by the International Kidney and Monoclonal Gammopathy Research Group. The classification published in 2019 has two main categories. The first category includes kidney damage caused by M-Ig with M-Ig deposits, or parts of it, in the kidneys. This category is further divided into two basic subcategories, organized and unorganized (amorphous) M-Ig deposits. The second category includes kidney damage caused by M-Ig without M-Ig deposits, or parts of it, in the kidneys. The goal of treatment of all forms of MGRS is to eradicate the cell clone that produces nephrotoxic FLC or nephrotoxic M-Ig. To achieve this goal, it is necessary to use the most effective drugs, which include anti-CD38 monoclonal antibodies. The aim of this article is to briefly inform about the morphological classification of MGRS and current treatments. Keywords: monoclonal gammopathy of renal significance
HLADINY A VÝZNAM VITAMINU D U PACIENTŮ S MALIGNÍMI LYMFOMY
Introduction: Vitamin D deficiency is associated in many diseases (including cancers and lymphomas) with worse prognosis. In our work, we wanted to analyze vitamin D levels in patients with non-Hodgkin lymphomas (NHL) of Czech Republic. Up to now, no similar data were published. Methods: We conducted a retrospective analysis of newly diagnosed NHL patients with known vitamin D concentration, micronutrients (selenium and zinc), albumin and IgG in plasma at the time before start of therapy. Our analysis included comparison of vitamin D levels in various lymphomas (aggressive vs. indolent), the association with demographic, clinical, and selected laboratory parameters, and also prognostic value of hypovitaminosis D in terms of survival (PFS and OS). Results: In time 05/2011 – 06/2020, 1196 patients were consecutively recruited (median age 65 years, 49,5% men), the median of vitamin D concentration was 43,5 nmol/l. Vitamin D deficiency (≤ 50nmol/l) was observed in 717/1196 (59,9%) cases, whereas patients with at least ≥75nmol/l (normal level) represented 14,1% cases only. Median follow-up was 3,9 years. We identified factors associated with vitamin D deficiency: female gender (p<0.000001), performance status ≥2 (p<0,0001), LDH > norm (p=0,0063), and hypoalbuminemia (p<0,000001). There were significantly lower vitamin D levels in aggressive (DLBCL, BL, PNBL, THL) vs. indolent lymphomas (FL, MZL; p=0.000002). In DLBCL, vitamin D deficiency correlated with shorter PFS and OS (median 5.15 yrs vs. not reached and 8.9 yrs vs. not reached; p<0.01), for FL there was no difference in PFS, but 5-year OS was 95% vs. 80% (p0.0007). Conclusion: Vitamin D deficiency is very frequent problem of the most patients with NHL in the time of initial diagnosis before start of therapy. The deficiency is associated with other negative prognostic factors (hypoalbuminemia, elevated LDH, worse performance status). Vitamin D deficiency is also associated with shorter overall survival and progression free survival.
vitamín D, Lymfomy, imunitní systém, prognóza
VITAMIN D AND ITS IMPORTANCE IN MALIGNANT LYMPHOMAS
Vitamin D is a group of steroid hormones, most of which is produced in the body with the help of UV radiation from the sun, but it is also contained in various foods such as marine fish oils. In the body, it is further metabolized to its active form in the liver and kidneys. It binds in the blood with the help of the VDBP (vitamin D binding protein) and acts on the VDR receptor (=Vitamin D Receptor) directly in the cell nucleus. Its concentration in blood is influenced by geographical location, season (length of sunshine), skin pigmentation, amount of fat and muscle tissue. Vitamin D best-known function is the regulation of calcium-phosphate metabolism, but it is involved in many other functions such as regulation of the cell cycle, induction of apoptosis and also plays a role in a regulation of the immune system. Briefly, its action leads rather to immune tolerance. Deficiency is becoming more and more common in the population, with almost 50% of the European population suffering from it today. Deficiency is associated with higher aggressiveness of tumors, including Non-Hodgkin lymphomas. Contrary, patients with higher levels of vitamin D have been shown to have better overall survival and time to progression. The question therefore arises as to whether vitamin D supplementation could have a more favorable effect on the prognosis.
Current experience with treatment of prognostically unfavorable acute myeloid leukemias with CPX-351 at the Institute of Hematology and Blood Transfusion
Therapeutic agent CPX-351, Vyxeos liposomal, is a newly approved drug intended for therapy of high-risk subtypes of acute myeloid leukemia (AML) sucha as AML arising from antecendent myelodsplastic syndrome or in connection with previous anticancer therapy. In the Czech Republic CPX-351 is reimbursed for patients aged 60 and over with above-mentioned AML subtypes. The following paper describes in its introduction the indication and dosage schedule of CPX-351, its mechanism of action and also briefly mentions the therapeutic results and safety profile of CPX-351 accoording to the product registration study. In the main part, the article describes current clinical experience with CPX-351 obtained since 2022 at the UHKT Prague and analyzes in detail case reports of two patients treated at the UHKT in last months. CPX-351 therapy represents, according to UHKTs experience so far, a relatively effective option for the treatment of high-risk AML in which treatment with standard chemotherapy often fails.
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Transfusion products and blood derivatives in the perspective of new European guidelines for severe bleeding
Major bleeding is one of the most serious emergencies in medicine. This situation requires multimodal therapy, which includes administering transfusion products and blood derivatives, standardized through guidelines. In the Czech Republic and Slovakia, the document "Diagnosis and Treatment of Life-Threatening Bleeding in Adult Patients in Intensive and Perioperative Care. Czech-Slovak Interdisciplinary Guideline" from 2017 is still valid. In 2023, an update of both European guidelines, from which the mentioned interdisciplinary procedure predominantly derives, was published. This work aims to identify and present changes in the European guidelines for severe bleeding since 2017. A total of 4 texts are included. Their analysis was divided according to individual transfusion products and blood derivatives. Besides introducing new European guidelines for treating severe bleeding, the work's text compares with the Czech-Slovak guideline from 2017.
bleeding, guidelines, blood transfusion, blood coagulation factors
Clonal mast cell disorders, hymenoptera venom allergy and venom immunotherapy
Introduction: Clonal mast cell disease and/or increased basal serum tryptase concentration are among the risk factors for a more severe life-threatening course of an anaphylactic reaction after a Hymenoptera insect sting. Because of the riskiness of these patients, the implementation of a single causal therapy – venom immunotherapy (VIT) should be recommended for each such patient. Material and methods: We created a prospective study consisting of 93 patients (58 men, 35 women) who met the indication criteria for VIT treatment. We included patients in the study gradually and data were collected from 2015 to 2023. We defined the basic characteristics of the group, we focused on the identification of patients with an elevated concentration of serum basal tryptase (˃ 8 ng/ml) and systemic mastocytosis, the specifics of the course of their systemic allergic reaction after a Hymenoptera insect sting, treatment tolerance, and occurrence of adverse effects. Results: From a total of 93 enrolled patients treated with VIT, we recorded persistently elevated concentrations of serum basal tryptase (sBT) ˃ 8 ng/ml in 15 patients (16,7 %). We diagnosed systemic mastocytosis in one patient. In a patient with elevated sBT values, we most often observed loss of consciousness and hypotension during a systemic allergic reaction after a Hymenoptera sting (p = ns). From the point of view of treatment tolerance, we observed a roughly comparable incidence of adverse effects in terms of local reactions. A total of 53,3 % of patients treated with VIT with elevated concentration of sBT overcame natural re-exposure to Hymenoptera insects, while not a single patient developed a systemic allergic reaction requiring the administration of an adrenaline autoinjector. Conclusion: Hymenoptera venom allergy is a life-threatening condition, and its occurrence is much more frequent, and the course is more severe in patients with elevated basal serum tryptase concentrations and/or clonal mast cell disease. In each patient with a confirmed clonal mast cell disease, it is necessary to search for the occurrence of an allergic reaction to Hymenoptera insect venom in the patient’s history and to consider the indication for venom immunotherapy as the only causal treatment. Key words: Clonal mast cell proliferation disorders, Hymenoptera venom, Venom immunotherapy, Systemic mastocytosis, Hereditary alpha-tryptasemia, Serum basal tryptase
clonal mast cell proliferation disorders
Comparison of two methods for measuring free hemoglobin in the supernatant of erythrocyte blood components
Background: The level of free hemoglobin (a marker of ongoing hemolysis) rises during the storage of erythrocyte transfusion components. The recommendation of the Council of Europe (Guide to the preparation, use and quality assurance of blood components, 21st Edition) and the Czech legislation (Regulation No. 143/2008 Coll.) define its maximum value at 0.8% of the erythrocyte mass at the end of the shelf life of the transfusion unit. Measuring the percentage of hemolysis is also recommended for blood components that are further treated, e.g. by washing. The aim of the study was to compare two methods of measuring free hemoglobin in the supernatant of erythrocyte transfusion components by direct spectrophotometry and to find out the suitability of the Harboe method to determine the level of free hemoglobin in transfusion units. Materials and methods: 20 units of erythrocyte transfusion components were included in the study. Samples of the supernatant were collected at the end of the expiration period and the free hemoglobin was measured by direct spectrophotometry by determining the absorbance of the sample at 540 nm according to Fortova (A) and by measuring the absorbance at wavelengths of 415 nm, 450 nm and 380 nm according to Harboe (B). The percentage of hemolysis of the erythrocyte mass was recalculated afterwards according to the volume and the hematocrit of the transfusion unit. Results: The level of free hemoglobin at the end of the storage period did not exceed 0.8% of the erythrocyte mass in all units - an average of 0.31% (A) and 0.29% (B). No statistically significant difference was discovered between the two sets. Conclusion: The method of measuring the absorbance at wavelengths of 415 nm, 450 nm and 380 nm according to Harboe corresponds to the commonly used method of measuring at 540 nm and is suitable for measuring the content of free hemoglobin in transfusion components.
Red cells – hemolysis – spectrophotometry
Primární mediastinální velkobuněčný B lymfom
Primary mediastinal large B cell lymphoma is an aggressive tumor diagnosis characterized by a rapid increase of tumor mass in the anterior mediastinum, occurring in younger patients. Currently, at the time of immunochemotherapy, 5-year overall survival of patients is 80-90%, however relapse of the disease occurs early, usually within one year of the end of therapy and the prognosis of these patients is unsatisfactory. Positron emission tomography combined with computed tomography using 18F-fluorodeoxyglucose is currently widely used not only at the time of diagnosis but also for monitoring of response to treatment. The FDG PET/CT examination has a strong prognostic significance at the time of diagnosis, during treatment and after termination. There is the high importance of the consideration between the maximum efficacy of the therapy and reduction of the long-term toxicity risk. Standard, anthracycline-based immunochemotherapy (R-CHOP, DA-EPOCH-R), autologous stem cell transplantation or consolidation radiotherapy for residual tumor mass are currently standard of the therapy. New therapy modalities (PD1 inhibitors, brentuximab vedotin or CAR T cell therapy) are available, but needed clinical trials are ongoing to assess the effectivity.
primary mediastinal large B cell lymphoma