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Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin) is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

Introduction: B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by an accumulation of long-lived, functionally inactive, mature-appearing neoplastic B-lymphocytes. It is associated with severe immunodeficiency. Chemotherapy or immunotherapy generally makes the immunodeficiency worse. JC virus (John Cunningham virus; JCV) is a type of human polyomavirus that causes the progressive multifocal leucoencephalopathy (PML). JCV is found in 70 to 90 percent of population. The virus remains in gastrointestinal tract or tubular cell of kidneys and may infect oligodendrocytes and astrocytes. Immunodeficiency or immunosupression associated with several drugs (e.g. monoclonal antibodies) or HIV infection allow the reactivation of JCV. Case-report: The authors present here a case of a 62-years old patient with B-CLL that was diagnosed 6 years ago. The patient underwent 4 courses of the first-line COP chemotherapy consisting of vincristine, cyclophosphamide and prednisone. A partial remission of the disease was achieved and the patient was on the maintenance therapy with chlorambucil for 5 years. The second-line COP chemotherapy and immunotherapy with rituximab was used because of B-CLL progression. Treatment was complicated with ischemic stroke and quadriparesis with left predominance. Magnetic resonance imaging (MRI) showed several cortical and subcortical lesions in frontal and parietal lobes bilaterally. Anticoagulation, vasodilatation and rehabilitation transitorily improved patient's clinical status. After the fifth course of immunotherapy, the patient suffered from dysarthria, disorientation and deterioration of personality. B-CLL infiltration of brain was suspected. The cerebrospinal fluid examination excluded central nervous system infiltration with B-CLL. MRI discovered progression of brain lesions and the diagnosis of PML was supposed. PCR detected the presence of JCV in cerebrospinal fluid and confirmed that diagnosis. Patient died in several weeks after diagnosis. Conclusion: Severe immunodeficiency during B-CLL treatment may lead to the reactivation of JCV in these patients and cause fatal PML. This work was supported by APVV 222-11; CEVYPET, and grant Vega 1/0016/12 projects. [ABSTRACT FROM AUTHOR]

Introduction: Hairy cell leukemia (HCL) is a rare indolent B-cell chronic lymphoproliferative disorder characterized by splenomegaly, pancytopenia, presence of hairy cells in peripheral blood/bone marrow and reactive marrow fibrosis. The annual incidence of HCL is estimated to be 0.3 cases per 100,000. The disease accounts for approximately 2-3% of all adult leukemias. The median age at diagnosis is 52 years. Materials and Methods: The aim of the present study was to compare the outcome of patients affected by typical HCL treated with cladribine. We retrospectively examined medical records of patients with HCL treated at the Department of Hematology and Transfusiology in Martin University Hospital between JAN 1998 to DEC 2012. We used Microsoft Office Excel for Mac 2011 (version 14.3.0) to do some basic data analysis. Results: The analysis included 11 patients (7 non-pretreated patients, 3 patients with relapse after previous treatment of cladribine, and 1 patient with progressive disease during a treatment with interferon). There were 4 women and 7 men. Mean age was 50.9 ± 13.3 years. All patients were treated with cladribine 0.14 mg/kg/day by subcutaneous bolus injections for five consecutive days. Cladribine caused predominantly hematological toxicity, in particular an initial neutropenia and long-lasting lymphocytopenia. Febrile neutropenia occurred in 3 patients during post-chemotherapy bone marrow suppression. The patient's condition has improved after administration of empiric antibiotic and antifungal therapy. Eleven (100%) patients achieved partial remission or minimal residual disease within three months of therapy. Conclusions: One course of cladribine given by subcutaneous bolus injections is very effective in HCL. Treatment appears to be safe, especially if associated with growth factors. However, longer follow-up is required to establish the real impact of this drug. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to analyse the outcomes of patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CAR-Tx), with a focus on outcomes after CAR T-cell failure, and to define the risk factors for rapid progression and further treatment., Methods: We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd-line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022., Results: The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression-free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty-three patients (59%) were refractory or relapsed after CAR-Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow-up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR-Tx. Risk factors for not receiving further therapy after CAR-Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS-2 (from R/P after CAR-Tx) was 6.7 months (6-month 57.9%) for treated patients and 0.4 months (6-month 4.2%) for untreated patients (p < 0.001). The median PFS-2 (from R/P after CAR-Tx) was 3.2 months (6-month 28.5%) for treated patients. The risk factors for a shorter PFS-2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS-2 for treated patients., Conclusion: Our findings allow better stratification of CAR-Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement)., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

The definition "Progressive Multifocal Leukoencephalopathy" (PML) was first used in 1958 to describe a fatal demyelinating central nervous system (CNS) disease in patients with lymphoproliferative disorders. In 1971, the virus responsible for the disease was isolated and named John Cunningham virus (JCV). We present a rare case of a 62-year-old male with chronic lymphocytic leukemia and PML. In our work, we discuss the diagnostic and therapeutic challenges and offer suggestions for preventing PML development. The main learning points are: 1. Regularly check the level of immunoglobulins and the CD4+ : CD8+ T-cell ratio, intravenous administration of immunoglobulins should be considered when recording their reduction. 2. In checking the CD4+ : CD8+ T-cell ratio and verifying the impossibility of raising the level of immunoglobulins, we must weigh the possible benefits of continuing treatment with monoclonal antibody against the risks. 3. Physicians should maintain a high index of suspicion for the development of PML in patients under treatment with monoclonal antibodies, especially when there is a new development of neurological signs or symptoms.Key words: JC virus - progressive multifocal leukoencephalopathy - recommendation - rituximab.

Introduction: Factor V Leiden (FVL) and prothrombin G20210A mutation (PTM) are the two most common genetic polymorphisms known to predispose to a first episode of venous thromboembolism (VTE). PTM is present in 2 % Caucasian population. The main aim of this study was to identify the PTM in the patients with positive history of thrombotic events vs. control subjects., Materials and Methods: The assessment of PTM was performed by the PCR analysis of the chromosomal DNA, which was isolated from the peripheral blood leukocytes., Results: Of the 2 274 patients included, 157 (6.9 %) were carriers of the PTM. The mutation was present only in 2.6 % (n = 8) of the 303 controls. The following clinical manifestations of PTM were analysed. We observed 123 venous thrombotic events, 46 arterial thrombosis and 14 spontaneous abortions. In this article we analyse other possible risk factors for thromboembolic events in patients with carriage of PTM., Conclusions: To our knowledge, this is the largest epidemiological study of PTM in Central Europe. Employing statistical analysis, we found relatively high prevalence of the PTM in both, the patients with positive thrombosis history (6.9 %), as well as in the control group (2.6 %). The risk of thrombosis by carriage of PTM is independent of age and gender. Study has shown relatively frequent presence of double carriership of PTM and factor V Leiden mutation (FVL).

The immune tolerance induction is the treatment of choice for the eradication of factor VIII inhibitors, a serious complication of inherited haemophilia A. Despite the preferred treatment of patients with good prognosis and testing of different regimens, the immune tolerance is achieved in 70-80%. Several modifications of regimens including the addition of immunomodulatory agents were proposed in order to improve immune tolerance induction (ITI) outcome. Intravenous immunoglobulin has complex immunomodulatory properties and has been used in immune tolerance induction since the introduction of Malmö regimen in the 1980s. The aim of the work is to evaluate the published evidence of its use in ITI in haemophilia A. In addition, the authors' own experience with a high-dose regimen using human plasma-derived factor VIII containing von Willebrand factor and pulsed IVIg is reported. The course of three patients with severe inherited haemophilia A and inhibitor (all high responders, two with poor prognosis, one with rescue treatment) is described. At least partial success was achieved in all patients and no adverse events attributable to intravenous immunoglobulin were observed. Despite the limited evidence, the addition of intravenous immunoglobulin appears to be a promising treatment modification for patients with poor prognosis or previous failure of immune tolerance induction.