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
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.
Copyright (c) 2025 Transfuze a hematologie dnes
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.
Copyright (c) 2024 Transfuze a hematologie dnes
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
FVIII activity measurement in patients with severe haemophilia A treated with EHL concentrates – selected assays results comparison
Introduction: The optimal substitutional treatment includes the FVIII activity (FVIII:C) measurement by the one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). However, with the advent of FVIII concentrates with an extended half-life, the problem of discrepancy between methods got worse due to the modifications of the FVIII molecule. Aim: Evaluation of the OSA and CSA discrepancy in patients treated with extended half-life FVIII concentrates. Method: The FVIII:C measurement by OSA with reagents Cephascreen® (Diagnostica Stago) and Pathromtin® SL (Siemens Healthineers) and by CSA BIOPHENTM FVIII:C (Hyphen BioMed) in patients treated with efmoroctocog alfa, rurioctocog alfa pegol, turoctocog alfa pegol and damoctocog alfa pegol. Results: The OSA and CSA results correlated with a good outcome for efmoroctocog alfa, the differences were up to 21 %. The results of rurioctocog alfa pegol in the range of 15–200 % were slightly lower by OSA with both reagents, on an average by 11 % and 18 %, while the results up to 10 % were higher by OSA with an average difference 54 % for Cephascreen® and up to 75 % for Pathromtin® SL. The resulst of turoctocog alfa pegol were lower by OSA in the range of 15–200 %, on an average by 36 % and 25 %. The samples with FVIII:C above 10 % of damoctocog alfa pegol were slightly higher by OSA (Cephascreen® by 18 %), but samples up to 10 % were significantly higher, with Cephascreen® on an average by 91 % and by 100 % with Pathromtin® SL. Conclusions: OSA Cephascreen® or Pathromtin® SL and CSA Hyphen correlate with a good outcome for efmoroctocog alfa. Of the other concentrates, the results correlate with a good outcome only for rurioctocog alfa pegol and damoctocog alfa pegol, and only the results of FVIII:C > 10 %.
Cryoglobulinemia from different medical point of view.
Summary Cryoglobulinemia from different medical point of view. Cryoglobulinemia is defined as the persistent presence of abnormal serum immunoglobulins that precipitate at low temperatures and dissolve again upon warming. Cryoglobulins may be composed by a monoclonal Ig (type I cryoglobulinemia), by a monoclonal Ig bound to the constant domain of polyclonal Ig heavy chains (type II cryoglobulinemia), or by polyclonal Igs (type III cryoglobulinemia). Cryoglobulinemia type II and III are called mixed cryoglobulinemia. Clinical manifestations of type I cryoglobulinemia are often related to intravascular obstruction, whereas those seen in the mixed cryoglobulinemias often originate in true immune complex-mediated vasculitis. The main clinical manifestations affect the skin (purpura, necrotic ulcers), joints, peripheral nervous system, and kidneys (membranoproliferative glomerulonephritis). Patients with type I and II cryoglobulinemia should be investigated for monoclonal gammopathy and lymphoproliferative diseases, Patients with type III cryoglobulinemia should be investigated for Hepatitis C, HIV and connective tissue disease. Keywords: cryoglobulin; monoclonal gammopathy; hepatitis C; vasculitis
Získaná trombotická trombocytopenická purpura
Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disease belonging to the group of thrombotic microangiopathies (TMA). It is characterised by the presence of microangiopathic haemolytic anaemia, severe thrombocytopenia and ischaemic end-organ damage. The underlying cause of the disease is a severe deficiency of von Willebrand factor cleaving metalloprotease. The enzyme deficiency causes the accumulation of large multimers of vWF to which platelets actively bind, with subsequent formation of microthrombi in the microcirculation. The most important test for the diagnosis of TTP is reduced ADAMTS13 enzyme activity below 10 % (0.1 IU/ml). Treatment of TTP should be initiated as early as possible when TTP is suspected, often before the ADAMTS13 activity results are known. The current standard of care for acute attacks of acquired TTP includes therapeutic plasma exchange, immunosuppression and caplacizumab. A rapid diagnosis of TTP, including ADAMTS13 activity testing, and early initiation of comprehensive treatment are critical to treatment success. Long-term monitoring of disease activity, including monitoring of ADAMTS13 activity, is also the necessary part of the treatment Key words: Thrombotic thrombocytopenic purpura, ADAMTS13, therapeutic plasma exchange, steroids, rituximab, caplacizumab.
Imúnna cytopénia u detí po transplantácii krvotvorných buniek
Immune cytopenia is a rare complication of hematopoietic stem cell transplantation. It is the result of dysregulation of immune system after the reconstitution of donor hematopoiesis. Current recommendations and guidelines for the diagnosis and treatment of the disease in pediatric transplantation are unclear, based on knowledge about autoimmune cytopenias without transplantation. Immune cytopenia associated with transplantation usually more often has a refractory and prolonged course, which confirms the different etiopathogenesis of the disease. Treatment includes a wide spectrum of approaches from observation to intensive management, especially in the case of coexistence of other peritransplantation complications. In addition to supportive treatment, patients may require modification of immunosuppression, in some cases, treatment focused on destruction of plasma cells or direct removal of auto- or alloantibodies from the bloodstream is also necessary. We provide a comprehensive view of the pathophysiology, treatment and prognosis of post-transplant immune cytopenias in children, also present our cohort. Keywords: immune-mediated cytopenia in childhood, hematopoietic cell transplantation, immune dysregulation, modification of immunosuppression, cohort of patients with immune cytopenia.
Therapeutic Plasma Exchange in the Treatment of Thrombotic Microangiopathies
Therapeutic plasma exchange (TPE) has an irreplaceable place in the treatment of some types of thrombotic microangiopathies, In the treatment of TTP, it has become the standard of care. TPE is defined by the American Society For Apheresis (ASFA) as a therapeutic extracorporeal procedure in which the patient's plasma is separated from other blood components. Although it is an invasive technique requiring a high quality of venous access, on the other hand, TPE is highly safe, and when performed correctly, complications are rare. It can be started within tens of minutes if necessary, and it has essentially no real contraindications. Separation of plasma from other blood components is ensured by centrifugation or membrane filtration. Crystaloids, 5 % albumin solution and freshly frozen donor plasma are used as a replacement solution in various proportions and combinations, or more recently, solvent-detergent-treated plasma is increasingly used. At least total plasma volume (TPV) of the patient should be replaced in one procedure, with less than 70 % of the TPV being replaced. It is important to remember to collect blood samples for ADAMTS13 and other tests, or preserve plasma samples, before starting TPE treatment, as interpretation of results from samples collected after TPE may be erroneous. The efficacy of TPE is determined by two mechanisms: 1) removal of the disease mediator or plasma components contributing to the pathogenesis of the condition, 2) delivery of the missing or dysfunctional plasma component when plasma is used as a replacement solution. The efficacy of TPE varies between forms of thrombotic microangiopathies, ranging from a clear and prompt effect in TTP to no effect in some forms of atypical haemolytic uraemic syndrome.
Autoinflamatorní choroby se symptomy, které připomínají maligním krevní choroby: syndrom Schnitzlerové, Stillova choroba dosplých, SAPHO a VEXAS syndrom. Přehled.
Autoinflammatory disorders with symptoms resembling malignant hematologic disease: Schnitzler syndrome, Adult onset Still disease, SAPHO and VEXAS syndrome. In this paper are described four autoinflammatory disorders with first manifestation in adults. All of them have some symptoms that resemble malignant hematologic disease. These disorders represent fascinating intersections of inflammation, hematologic abnormalities, and clinical complexity. Schnitzler syndrome is characterized by a combination of monoclonal gammopathy (specifically IgM gammopathy) and autoinflammatory symptoms. Patients experience systemic inflammation affecting the skin, and bone pain. Various clinical diagnoses, including Sweet syndrome, urticaria, and others, may be assigned. Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disorder with persistent high fever is a hallmark, joint inflammation and salmon-coloured rash, fatigue, sore throat, and lymphadenopathy. VEXAS syndrome is a monogenic disease of adulthood. It results from somatic mutations in UBA1 within hematopoietic progenitor cells. Patients develop inflammatory symptoms affecting various organs, including the skin, lungs, blood vessels, and cartilage. Myeloid-driven autoinflammation and progressive bone marrow failure contribute to substantial morbidity and mortality. SAPHO syndrome is a rare condition characterized by a combination of osteitis, osteolytic bone destruction osteoarticular and dermatologic features. SAPHO syndrome induces inflammatory bone lesions (osteolytic or hyperostosis) and joint pain (synovitis). Skin manifestations includes acne and pustulosis. Only VEXAS syndrome have diagnostic UBA1 mutation, four tree other diagnostic criteria are used. The last diagnostic and therapeutic options are discussed in this review.
syndrom Schnitzlerové; Adult Onset Still Disease (AOSD); VEXAS syndrom; SAPHO syndrom.
Trombotické mikroangiopatie v dětském věku
Thrombotic microangiopathy (TMA) is a pathological lesion triggered by endothelial injury or dysfunction. TMA occurs in wide range of diseases and is characterized by microangiopathic hemolytic anemia, thrombocytopenia and ischemic organ injury due to thrombosis in microvasculature. In pediatric age, TMA is observed as primary, i.e. congenital form as secondary, acquired form - especially linked to E. coli infection. Understanding of epidemiology, pathophysiology, laboratory and clinical signs and differential diagnosis is crucial for early and on-time specific diagnostic approach of this life-threatening diseases.
trombotická mikroangiopatie, hemolyticko-uremický syndrom, trombotická trombocytopenická purpura, děti, adolescenti
Cryopreservation of hematopoietic cells from unrelated donors from the Czech National Bone Marrow Donor Registry in the context of COVID-19 pandemic: are there useless collections?
One of the responses the COVID-19 pandemic has been a worldwide increase the number of cryopreserved hematopoietic cells from unrelated donors, mainly due to poorer availability of donors and problems with product transportation. Although cryopreservation is logistically advantageous, the higher risk of not using graft cannot be ignored. We retrospectively evaluated the cryopreservation of donors from the Czech National Register of Bone Marrow Donors (CNMDR) in the period before, during and after the COVID-19 and analyzed unused grafts, including the reasons. The primary goal was to evaluate how cryopreserved grafts collected in given periods for transplant centers(TC) in the Czech Republic and abroad has changed. Of the total number of 374 grafts collected in the period 2018-2023, 72(19%) were cryopreserved. In the period before the pandemic (2018-2/2020), 152 grafts collected and only 2 cryopreservations performed(1.3%), 1 for TC in the CR and 1 for foreign. During the period of the COVID-19 pandemic (3/2020-2022), a total of 144 grafts collected, 58 cryopreserved(40%), 28(19%) for patients from CR and 20(14%) for forein. In the post-pandemic (year 2023), 78 grafts taken, 22 cryopreserved(28%), 8(10%) for patients from CR and 14(18%) for patients from abroad. For period 2018-2023, 3 grafts (0.8%) were not used, all from the period of COVID-19 (1 from 2020 and 2 from 2022) and were collected for patients from foreign TCs. The reason for not-used grafts was in 2 cases death of the patient and 1 patient refused transplant. Our analysis shows a decrease in cryopreserved grafts in the post-pandemic period for patients from CR, while for patients from foreign TCs continues to show a sleightly upward trend. Despite the detected low percentage of unused grafts, it is necessary to perceive the negative ethical impact of the destruction of the graft from the point of view of the donors.
Použití plné krve u pacientů se život ohrožujícím krvácením v důsledku traumatu: souhrn a konsenzus jednání mezioborového panelu
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