Publications by authors named "Jiri Mayer"

Chronic myeloid leukemia (CML) treatment has been revolutionized over last 20 years because of tyrosine kinase inhibitors (TKIs) and patients with CML now have life expectancy of general population. Chronic TKI treatment may cause adverse effects (AEs) that vary in frequency and severity. Nilotinib shows common AEs with metabolic changes and skin AEs.

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The influence of t(v;22) sole, major route ACAs all (+8, n = 14; +Ph, n = 10; +19, n = 1), and -Y sole on progression-free survival. Survival curves are compared with those of patients with the standard t(9;22) translocation. Other ACAs or complex karyotypes did not influence survival.

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Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 10/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19).

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Patient-derived xenografts (PDXs) can be improved by implantation of a humanized niche. Nevertheless, the overall complexity of the current protocols, as well as the use of specific biomaterials and procedures, limits the wider adoption of this approach. Here, we identify the essential minimum steps required to create the humanized scaffolds and achieve successful acute myeloid leukemia (AML) engraftment.

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Community-acquired respiratory viral infections (CARV) significantly impact patients with hematological malignancies (HM), leading to high morbidity and mortality. However, large-scale, real-world data on CARV in these patients is limited. This study analyzed data from the EPICOVIDEHA-EPIFLUEHA registry, focusing on patients with HM diagnosed with CARV during the 2023-2024 autumn-winter season.

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Background: Up to 65% of patients with chronic myeloid leukemia (CML) who are treated with imatinib do not achieve sustained deep molecular response, which is required to attempt treatment-free remission. Asciminib is the only approved BCR::ABL1 inhibitor that Specifically Targets the ABL Myristoyl Pocket. This unique mechanism of action allows asciminib to be combined with adenosine triphosphate-competitive tyrosine kinase inhibitors to prevent resistance and enhance efficacy.

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Article Synopsis
  • Since 2017, combining targeted therapies with traditional chemotherapy has led to better outcomes for acute myeloid leukemia (AML) patients.
  • A study of 5,359 AML patients over 20 years used data from the HARMONY Alliance to analyze treatment outcomes during four 5-year periods from 1997 to 2016.
  • Results show significant improvements in 5-year survival rates and reduced 60-day mortality (from 13.0% to 4.7%), even across different genetic risk groups, indicating that the advancements in treatment have positively affected patient outcomes.
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Bruton tyrosine kinase (BTK) inhibitor therapy induces peripheral blood lymphocytosis in chronic lymphocytic leukemia (CLL), which lasts for several months. It remains unclear whether nongenetic adaptation mechanisms exist, allowing CLL cells' survival during BTK inhibitor-induced lymphocytosis and/or playing a role in therapy resistance. We show that in approximately 70% of CLL cases, ibrutinib treatment in vivo increases Akt activity above pretherapy levels within several weeks, leading to compensatory CLL cell survival and a more prominent lymphocytosis on therapy.

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Objective: We report patient-reported outcomes (PROs) measuring health-related quality of life (HRQoL) from the ROSEWOOD trial (NCT03332017), which demonstrated superior efficacy and a manageable safety profile with zanubrutinib plus obinutuzumab (ZO) versus obinutuzumab (O) in patients with heavily pretreated relapsed/refractory follicular lymphoma (R/R FL).

Methods: PROs were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) and EQ-5D-5L questionnaires at baseline and subsequently every 12 weeks. All QLQ-C30 domains and EQ-5D-5L visual analog scale (VAS) scores were analyzed descriptively.

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The ALPINE trial established the superiority of zanubrutinib over ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma; here, we present data from the final comparative analysis with extended follow-up. Overall, 652 patients received zanubrutinib (n = 327) or ibrutinib (n = 325). At an overall median follow-up of 42.

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This study compared decitabine exposure when administered IV (DEC-IV) at a dose of 20 mg/m for 5-days with orally administered decitabine with cedazuridine (DEC-C), as well as the clinical efficacy and safety of DEC-C in patients with acute myeloid leukaemia (AML) who were ineligible for intensive induction chemotherapy. In all, 89 patients were randomised 1:1 to DEC-IV or oral DEC-C (days 1-5 in a 28-day treatment cycle), followed by 5 days of the other formulation in the next treatment cycle. All patients received oral DEC-C for subsequent treatment cycles until treatment discontinuation.

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Purpose: To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m with 90 mg/m daunorubicin in the first 7 + 3 induction and one versus two cycles of 7 + 3 induction.

Patients And Methods: Patients age 18-65 years with newly diagnosed AML were randomly assigned to 60 versus 90 mg/m daunorubicin once daily plus cytarabine. Patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle.

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Background: To evaluate the outcomes of first-line imatinib versus nilotinib treatment for chronic myeloid leukemia in the chronic phase (CML-CP) in real-world clinical practice.

Methods: A propensity score analysis was performed to eliminate imbalances between the treatment groups. In the analysis, 163 patients in the nilotinib group and 163 patients in the matched imatinib group were retrospectively evaluated.

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Article Synopsis
  • * Antifungal prophylaxis has reduced IFD occurrences but has also changed the types of fungal pathogens seen, necessitating broader screening methods for early diagnosis and treatment.
  • * A study analyzed blood samples from high-risk patients using advanced PCR techniques, revealing that many detectable fungi were typically non-pathogenic, highlighting the need for repeated testing and accurate identification to guide effective treatment.
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  • - Our study looked at fungal infections in patients with acute myeloid leukemia being treated with venetoclax and azacitidine, comparing those who received antifungal prophylaxis (AFP) to those who didn't.
  • - Out of 186 patients, only 1 out of 85 (1%) with AFP developed a fungal infection, while 5 out of 101 (5%) without AFP got infected, showing no significant difference between the two groups.
  • - Overall, the study found that fungal infections were mostly mild and appeared early in treatment, and they did not significantly impact patient survival or death rates.
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Limited data is available on the health-related quality of life (HRQoL) and symptoms of patients with chronic myeloid leukemia (CML) who are in treatment-free remission (TFR). We herein report HRQoL results from the EURO-SKI trial. Patients who had been on tyrosine kinase inhibitors (TKIs) therapy for at least 3 years and achieved MR4 for at least 1 year were enrolled from 11 European countries, and the EORTC QLQ-C30 and the FACIT-Fatigue questionnaires were used to assess HRQoL and fatigue respectively.

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Several in vitro models have been developed to mimic chronic lymphocytic leukemia (CLL) proliferation in immune niches; however, they typically do not induce robust proliferation. We prepared a novel model based on mimicking T-cell signals in vitro and in patient-derived xenografts (PDXs). Six supportive cell lines were prepared by engineering HS5 stromal cells with stable expression of human CD40L, IL4, IL21, and their combinations.

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Article Synopsis
  • * The study included 201 patients receiving asciminib and 204 receiving investigator-selected TKIs, with results showing a higher major molecular response at week 48 for asciminib (67.7%) versus TKIs (49.0%), highlighting its potential advantages.
  • * Asciminib also outperformed imatinib specifically, achieving a major molecular response in 69.3% of patients, compared to 40.2% with imatinib, suggesting it may be
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Blast phase (BP) of chronic myeloid leukemia (CML) still represents an unmet clinical need with a dismal prognosis. Due to the rarity of the condition and the heterogeneity of the biology and clinical presentation, prospective trials and concise treatment recommendations are lacking. Here we present the analysis of the European LeukemiaNet Blast Phase Registry, an international collection of the clinical presentation, treatment and outcome of blast phases which had been diagnosed in CML patients after 2015.

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  • The COVID-19 pandemic has severely affected individuals with hematological malignancies due to their weakened immune systems, resulting in higher mortality rates and severe outcomes.
  • Data from the EPICOVIDEHA registry, which compiles COVID-19 cases from these patients worldwide, was collected from 2020 to 2022, including 8,767 cases from 152 centers across 41 countries.
  • Findings show a significant drop in critical infections and overall mortality rates, but hospitalization (especially in ICU) remains a serious risk factor; vaccination is linked to better survival outcomes, highlighting the need for ongoing monitoring and support for these patients.
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  • * An analysis of data from the SIMPLIFY-1 trial showed that momelotinib led to better outcomes, such as higher rates of transfusion independence and more stable transfusion needs, especially in patients with moderate to severe anemia (hemoglobin <12 g/dL).
  • * Safety profiles for momelotinib remained consistent with previous findings, indicating that it offers benefits for spleen size, symptoms, and anemia for previously untreated patients, regardless of their baseline hemoglobin levels. *
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  • - The EURO-SKI study, the largest clinical trial on stopping tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia, involved 728 patients and found that 61% maintained major molecular response (MMR) at 6 months and 46% at 36 months.
  • - Key factors influencing MMR maintenance included the length of TKI treatment and the patient's deep molecular remission duration before stopping treatment, along with the type of leukemia transcript.
  • - For patients experiencing late MMR losses, factors like TKI treatment duration, the presence of blasts in blood, and platelet counts at diagnosis were significant predictors of outcomes during the 36-month follow-up.
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Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) toward precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifier genes and activated signaling/myeloid transcription factors (AS/MTFs) with disease progression and treatment failure in patients with CML after tyrosine kinase inhibitor (TKI) therapy.

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