Publications by authors named "Valkovic T"

Multiple myeloma (MM) is a hematologic disease characterized by the clonal expansion of malignant plasma cells that accumulate in the bone marrow, leading to osteolytic bone disease, hypercalcemia, anemia, and renal dysfunction. Daratumumab was the first monoclonal anti-CD38 antibody approved for the treatment of MM, initially in relapse/refractory settings and, more recently, for newly diagnosed patients. Increased first-line usage of daratumumab will also substantially change treatment approaches for patients with relapsed/refractory disease.

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Obinutuzumab was approved for front-line treatment of chronic lymphocytic leukemia in combination with chlorambucil pulses administered every 2 wks. Alternative schedules of chlorambucil enable the administration of higher total chlorambucil doses, and have better antileukemia activity. So far, evidence on the feasibility of combining obinutuzumab with alternative chlorambucil schedules is lacking.

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: Ixazomib, used in combination with lenalidomide and dexamethasone (IRd), has shown efficacy in clinical trials for relapsed/refractory multiple myeloma (RRMM). : This study evaluates the real-world effectiveness and safety of IRd in Croatian RRMM patients. A retrospective analysis was conducted on 164 RRMM patients treated with ixazomib at nine Croatian haematology centres from November 2016 to February 2023.

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Background: Bortezomib, dexamethasone and cyclophosphamide (VCd) remains a popular regimen, due to its activity and low toxicity, while bortezomib, lenalidomide and dexamethasone (VRd) is widely used in US and Europe; both are combined with anti-CD38 monoclonal antibodies but VCd and VRd have not been compared directly in adequately powered prospective trials.

Aim: We compared the outcomes of 1216 patients treated with VCd (N = 690) or VRd (N = 526) in a real-world setting.

Results: Patients treated with VCd had more often severe renal dysfunction, ISS-3 disease, hypercalcemia, elevated LDH, anemia, thrombocytopenia, poor performance while VRd-treated were older and received less often autologous transplant but more frequently maintenance but the duration of induction was similar.

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Multiple myeloma is among the most common hematological malignancies and is characterized by a strong susceptibility to infections primarily bacterial and viral and, to a much lesser extent, fungal. There appears to be a slightly increasing frequency of invasive fungal infections. This is attributed to the use of different combinations of newer drugs and patients' exposure to increasing therapeutic lines, and thus to risk factors for invasive fungal infections, especially severe and long-term neutropenia.

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Article Synopsis
  • 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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  • Patients with lymphoid malignancies experience higher death and prolonged infection rates from COVID-19, with conflicting data on how different treatments affect these outcomes.
  • A study of 314 patients showed that untreated or off-treatment patients had higher mortality (15-16%) compared to those on treatment (35%), while prolonged infections were notably more common in patients using anti-CD20 antibodies like obinutuzumab.
  • Key risk factors for increased mortality were older age and the use of purine analogues, while treatment type didn't significantly impact death rates, indicating that treatment choices must consider these epidemiological risks.
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Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world.

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Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail.

Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022.

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Cases with low level V617F mutations are increasingly detected; however, the clinical interpretation of the low allele burden may be challenging. The aim of this study is to analyze and compare the bone marrow morphology and peripheral blood findings in the low level V617F allele burden (≤15% of ) and high V617F mutation burden patients (>15% ). In total, 122 V617F positive cases with concomitant bone marrow biopsies and peripheral blood findings were re-evaluated (62 low and 60 high level V617F positive).

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Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients.

Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022.

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Non-Hodgkin lymphomas are most frequently classified based on the lineage marker expression. However, lymphomas with aberrant marker expression as well as monoclonal Κ and gene rearrangements may co-exist which can be misleading and confusing. Primary CD20 negative diffuse large B-cell lymphomas (DLBCL) represent a rare entity, and they account for 1% to 3% of cases.

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Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.

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Article Synopsis
  • Disease and treatment-related immunodeficiencies can reduce the effectiveness of SARS-CoV-2 vaccines in patients with hematologic diseases, as demonstrated in a study of 118 individuals.
  • After the first vaccine dose, only 33% of patients showed positive antibody responses, but this increased to 64.4% and a higher antibody titer after the second dose.
  • Seropositivity rates varied significantly among different hematologic conditions, with lower rates observed in lymphoma and chronic lymphocytic leukemia, emphasizing the need for tailored vaccination strategies for patients based on their specific diagnoses.
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  • * The study noted that only 16.2% of the patients were vaccinated with two or more doses prior to COVID-19 diagnosis, and vaccination status was linked to lower mortality rates.
  • * Key risk factors for increased mortality included older age, active malignancy, severe COVID-19 symptoms, and ICU admission, with additional findings showing no significant difference in survival rates between NHL and CLL patients.
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  • * The Omicron variant was the most common strain detected (68.7%), with a notable 9% mortality rate within 30 days of diagnosis, which is lower compared to the pre-vaccine era's 31%.
  • * Factors like older age, active HM, and severe COVID-19 increased mortality, while treatment with monoclonal antibodies reduced the death rate, demonstrating that even vaccinated patients with HM remain at significant risk for severe outcomes.
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Iron is an essential trace metal necessary for the reproduction and survival of fungal pathogens. The latter have developed various mechanisms to acquire iron from their mammalian hosts, with whom they participate in a continuous struggle for dominance over iron. Invasive fungal infections are an important problem in the treatment of patients with hematological malignancies, and they are associated with significant morbidity and mortality.

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Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality.

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  • Hodgkin lymphoma (HL) is a rare type of cancer mostly found in the lymph nodes, with very few cases involving areas outside the lymphatic system, unlike non-Hodgkin lymphoma.
  • The report describes a rare case of primary classical Hodgkin lymphoma in the soft tissue of a 78-year-old man's buttock, which is an unusual location for this type of cancer.
  • The case presented diagnostic challenges during a fine-needle biopsy, which initially suggested a low-grade sarcoma, but a surgical biopsy and immunohistochemistry eventually led to the correct diagnosis and informed successful treatment.
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Modic changes (MCs) have attracted great interest in recent years. The complex process of MC development and progression seems to involve interplay between mechanical, infective, inflammatory, and degenerative processes that cannot be clearly differentiated. Based on signal intensity on T1- and T2-weighted MRI scans, MCs can be divided three types: Type 1, Type 2, and Type 3.

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Based on our earlier research into the main characteristics and risk factors for infections in hospitalized patients with multiple myeloma, we created the numerical Multiple Myeloma Index for Risk of Infection (MMIRI) to predict infection in myeloma patients. The included factors that could influence the pathogenesis and incidence of infections were sex, performance status, Durie Salmon stage of disease, International Staging System, serum creatinine level, immune paresis, neutropenia, serum ferritin level, the presence of any catheters, disease duration, stable/progressive disease, and type of therapy. For each of these parameters, the strength of association with infection was statistically estimated and specific number of points was assigned to each of these parameters, proportional to the strength of the association.

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