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  1. Article ; Online: Alternative Dosing Schedules of Azacitidine: A Real-World Study Across South American Centers.

    Castelo, Lucas / da Silva, Wellington Fernandes / Lincango, Marco / Buccheri, Valeria / Perusini, Agustina / Arbelbide, Jorge / Iastrebner, Marcelo / Gonzalez, Jacqueline / Pereyra, Patricio / Pereira, Thales Dalessandro M / Marchi, Luan Lima / Rocha, Vanderson / Belli, Carolina B / Velloso, Elvira Deolinda Rodrigues Pereira

    Clinical lymphoma, myeloma & leukemia

    2024  

    Language English
    Publishing date 2024-02-14
    Publishing country United States
    Document type Letter
    ZDB-ID 2540992-X
    ISSN 2152-2669 ; 2152-2650
    ISSN (online) 2152-2669
    ISSN 2152-2650
    DOI 10.1016/j.clml.2024.02.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 5903: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Risk factors and incidence of thrombosis in a Brazilian cohort of patients with Philadelphia-negative myeloproliferative neoplasms.

    Seguro, Fernanda Salles / Teixeira, Larissa Lane Cardoso / da Rosa, Lidiane Inês / da Silva, Wellington Fernandes / Nardinelli, Luciana / Bendit, Israel / Rocha, Vanderson

    Journal of thrombosis and thrombolysis

    2020  Volume 49, Issue 4, Page(s) 667–672

    Abstract: Few data are available regarding epidemiology and outcomes of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) in Latin America. Therefore, current models for MPN treatment are based in large cohorts of patients from Europe and North ... ...

    Abstract Few data are available regarding epidemiology and outcomes of Philadelphia-negative chronic myeloproliferative neoplasms (MPN) in Latin America. Therefore, current models for MPN treatment are based in large cohorts of patients from Europe and North America. In this paper, we conducted a retrospective study to evaluate thrombotic and bleeding events in a cohort of patients with MPN from a reference center in Brazil. A total of 334 patients were included, being essential thrombocythemia the most common diagnosis. Here, we found that 41% of the MPN patients had a thrombotic event prior to the diagnosis. Thrombosis was more frequent in patients under 60 years-old. In a multivariable model, only JAK2 V617F mutation (OR 2.57 95% CI 1.58-4.18, p < 0.001) and presence of two cardiovascular risk factors (OR 1.90 95% CI 1.21-2.98, p < 0.005) were significant for thrombosis. The risk of thrombosis was similar among all subtypes of MPN. Cumulative incidence of thromboembolic event at 5 years from diagnosis was 5.8% (95% CI 3.5-8.9), which is similar to previous studies. The high incidence of thromboembolic events in younger patients suggests that socioeconomic disparities might have a role in the outcomes of MPN.
    MeSH term(s) Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brazil/epidemiology ; Female ; Hemorrhage/epidemiology ; Hemorrhage/etiology ; Humans ; Incidence ; Male ; Middle Aged ; Myeloproliferative Disorders/complications ; Myeloproliferative Disorders/mortality ; Myeloproliferative Disorders/therapy ; Retrospective Studies ; Risk Factors ; Thrombosis/epidemiology ; Thrombosis/etiology ; Young Adult
    Language English
    Publishing date 2020-01-03
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1230645-9
    ISSN 1573-742X ; 0929-5305
    ISSN (online) 1573-742X
    ISSN 0929-5305
    DOI 10.1007/s11239-019-02029-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 4352: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Predictive factors associated with induction-related death in acute myeloid leukemia in a resource-constrained setting.

    Mendes, Fernanda Rodrigues / da Silva, Wellington Fernandes / da Costa Bandeira de Melo, Raphael / Silveira, Douglas Rafaele Almeida / Velloso, Elvira Deolinda Rodrigues Pereira / Rocha, Vanderson / Rego, Eduardo Magalhaes

    Annals of hematology

    2021  Volume 101, Issue 1, Page(s) 147–154

    Abstract: Despite advances in supportive measures, acute myeloid leukemia (AML) remission induction still has a high mortality rate in real-world studies as compared to prospective reports. We analyzed data from 206 AML adult patients treated with conventional ... ...

    Abstract Despite advances in supportive measures, acute myeloid leukemia (AML) remission induction still has a high mortality rate in real-world studies as compared to prospective reports. We analyzed data from 206 AML adult patients treated with conventional chemotherapy. The primary endpoint was the 60-day mortality rate, aiming to find risk factors and to examine the role of anti-infection prophylaxis. The 60-day mortality rate was 26%, raising to 41% among those older than 60 years. Complete response was documented at the end of induction in 49%. The final survival model showed that age > 60 years (HR 3.2), Gram-negative colonization (HR 3), monocytic AML (HR 1.8), C-reactive protein (CRP) > 15 mg/dL (HR 10), and an adverse risk in the genetic stratification (HR 3) were associated with induction death. Multidrug-resistant bacteria colonization, thrombosis, and AKI were documented in 71%, 12%, and 66% of the cohort, respectively. Antibacterial and antifungal prophylaxis did not improve outcomes in this study. Our report corroborated the higher mortality during AML induction compared to real-world data from the USA and Europe. In line with other publications, age and cytogenetic stratification influenced early death in this cohort. Noticeably, Gram-negative colonization, monocytic AML, and CRP were also significant to early mortality.
    MeSH term(s) Adolescent ; Adult ; Age Factors ; Aged ; Anti-Infective Agents/therapeutic use ; Antineoplastic Agents/therapeutic use ; Female ; Humans ; Leukemia, Myeloid, Acute/diagnosis ; Leukemia, Myeloid, Acute/mortality ; Leukemia, Myeloid, Acute/therapy ; Male ; Middle Aged ; Mortality ; Prognosis ; Remission Induction/methods ; Retrospective Studies ; Risk Factors ; Treatment Outcome ; Young Adult
    Chemical Substances Anti-Infective Agents ; Antineoplastic Agents
    Language English
    Publishing date 2021-10-21
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-021-04687-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.181: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: The PIP4K2 inhibitor THZ-P1-2 exhibits antileukemia activity by disruption of mitochondrial homeostasis and autophagy.

    Lima, Keli / Pereira-Martins, Diego Antonio / de Miranda, Lívia Bassani Lins / Coelho-Silva, Juan Luiz / Leandro, Giovana da Silva / Weinhäuser, Isabel / Cavaglieri, Rita de Cássia / Leal, Aline de Medeiros / da Silva, Wellington Fernandes / Lange, Ana Paula Alencar de Lima / Velloso, Elvira Deolinda Rodrigues Pereira / Griessinger, Emmanuel / Hilberink, Jacobien R / Ammatuna, Emanuele / Huls, Gerwin / Schuringa, Jan Jacob / Rego, Eduardo Magalhães / Machado-Neto, João Agostinho

    Blood cancer journal

    2022  Volume 12, Issue 11, Page(s) 151

    Abstract: The treatment of acute leukemia is challenging because of the genetic heterogeneity between and within patients. Leukemic stem cells (LSCs) are relatively drug-resistant and frequently relapse. Their plasticity and capacity to adapt to extracellular ... ...

    Abstract The treatment of acute leukemia is challenging because of the genetic heterogeneity between and within patients. Leukemic stem cells (LSCs) are relatively drug-resistant and frequently relapse. Their plasticity and capacity to adapt to extracellular stress, in which mitochondrial metabolism and autophagy play important roles, further complicates treatment. Genetic models of phosphatidylinositol-5-phosphate 4-kinase type 2 protein (PIP4K2s) inhibition have demonstrated the relevance of these enzymes in mitochondrial homeostasis and autophagic flux. Here, we uncovered the cellular and molecular effects of THZ-P1-2, a pan-inhibitor of PIP4K2s, in acute leukemia cells. THZ-P1-2 reduced cell viability and induced DNA damage, apoptosis, loss of mitochondrial membrane potential, and the accumulation of acidic vesicular organelles. Protein expression analysis revealed that THZ-P1-2 impaired autophagic flux. In addition, THZ-P1-2 induced cell differentiation and showed synergistic effects with venetoclax. In primary leukemia cells, LC-MS/MS-based proteome analysis revealed that sensitivity to THZ-P1-2 is associated with mitochondrial metabolism, cell cycle, cell-of-origin (hematopoietic stem cell and myeloid progenitor), and the TP53 pathway. The minimal effects of THZ-P1-2 observed in healthy CD34<sup>+</sup> cells suggest a favorable therapeutic window. Our study provides insights into the pharmacological inhibition of PIP4K2s targeting mitochondrial homeostasis and autophagy, shedding light on a new class of drugs for acute leukemia.
    MeSH term(s) Humans ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Autophagy ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/metabolism ; Apoptosis ; Homeostasis
    Language English
    Publishing date 2022-11-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2600560-8
    ISSN 2044-5385 ; 2044-5385
    ISSN (online) 2044-5385
    ISSN 2044-5385
    DOI 10.1038/s41408-022-00747-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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