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  1. Article ; Online: Blinatumomab before allogeneic stem cell transplantation: the ideal strategy to improve patient's outcomes?

    Locatelli, Franco

    Transplantation and cellular therapy

    2023  Volume 30, Issue 2, Page(s) 129–130

    MeSH term(s) Humans ; Hematopoietic Stem Cell Transplantation ; Antibodies, Bispecific/therapeutic use
    Chemical Substances blinatumomab (4FR53SIF3A) ; Antibodies, Bispecific
    Language English
    Publishing date 2023-10-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3062231-1
    ISSN 2666-6367
    ISSN (online) 2666-6367
    DOI 10.1016/j.jtct.2024.01.061
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5082: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Is the age of vincristine/steroid pulses over?

    Locatelli, Franco

    Blood

    2023  Volume 141, Issue 24, Page(s) 2914–2915

    MeSH term(s) Child ; Humans ; Vincristine ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Steroids ; B-Lymphocytes
    Chemical Substances Vincristine (5J49Q6B70F) ; Steroids
    Language English
    Publishing date 2023-06-14
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023020241
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  3. Article ; Online: Exposure-safety relationship for patients with primary hemophagocytic lymphohistiocytosis treated with emapalumab.

    Jordan, Michael B / Locatelli, Franco

    Pediatric blood & cancer

    2023  Volume 71, Issue 2, Page(s) e30778

    Abstract: Primary hemophagocytic lymphohistiocytosis (pHLH) is an immune-mediated, hyperinflammatory disorder. Interferon-γ (IFNγ) plays a key role in the pathophysiology of pHLH. Emapalumab, a fully human, anti-IFNγ monoclonal antibody neutralizes both free and ... ...

    Abstract Primary hemophagocytic lymphohistiocytosis (pHLH) is an immune-mediated, hyperinflammatory disorder. Interferon-γ (IFNγ) plays a key role in the pathophysiology of pHLH. Emapalumab, a fully human, anti-IFNγ monoclonal antibody neutralizes both free and receptor-bound IFNγ. However, inhibiting IFNγ-mediated signaling could result in immune dysfunction and immunosuppression. This exploratory exposure-safety analysis investigated the relationship between emapalumab and the incidence of adverse events in patients with pHLH. Increased exposure to emapalumab was not associated with an increased predicted risk of severe adverse events, infection, or infusion-related reactions. Emapalumab was associated with a favorable and manageable safety profile across all assessed doses and treatment durations.
    MeSH term(s) Humans ; Lymphohistiocytosis, Hemophagocytic/chemically induced ; Lymphohistiocytosis, Hemophagocytic/drug therapy ; Lymphohistiocytosis, Hemophagocytic/complications ; Antibodies, Monoclonal/adverse effects ; Antibodies, Neutralizing/therapeutic use ; Interferon-gamma
    Chemical Substances Emapalumab ; Antibodies, Monoclonal ; Antibodies, Neutralizing ; Interferon-gamma (82115-62-6)
    Language English
    Publishing date 2023-11-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2131448-2
    ISSN 1545-5017 ; 1545-5009
    ISSN (online) 1545-5017
    ISSN 1545-5009
    DOI 10.1002/pbc.30778
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    Zs.A 1131: Show issues Location:
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  4. Article ; Online: Venetoclax, a new player in the treatment of children with high-risk myeloid malignancies?

    Masetti, Riccardo / Baccelli, Francesco / Leardini, Davide / Locatelli, Franco

    Blood advances

    2024  

    Abstract: Venetoclax selectively inhibits BCL-2 and restores apoptotic signaling of hematological malignant cells. Venetoclax in combination with hypomethylating and low-dose cytotoxic agents has revolutionized the management of elderly patients affected by acute ... ...

    Abstract Venetoclax selectively inhibits BCL-2 and restores apoptotic signaling of hematological malignant cells. Venetoclax in combination with hypomethylating and low-dose cytotoxic agents has revolutionized the management of elderly patients affected by acute myeloid leukemia (AML), as well as that of patients unfit to receive intensive chemotherapy. In a single phase 1 pediatric trial conducted on relapsed/refractory AML, the combination of venetoclax with intensive chemotherapy was shown to be safe and yielded promising response rates. In addition, several retrospective studies in children with AML reported that venetoclax combined with hypomethylating agents and cytotoxic drugs appears a safe and efficacious bridge to transplant. Promising results on the use of venetoclax combinations in advanced myelodysplastic syndromes (MDS) and therapy-related MDS/AML have also been reported in small case series. This review summarizes the available current knowledge about venetoclax use in childhood high-risk myeloid neoplasms, discussing a possible integration of BCL-2 inhibition in the current treatment algorithm of these children. It also focuses on specific genetic subgroups potentially associated with response in preclinical and clinical studies.
    Language English
    Publishing date 2024-05-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2915908-8
    ISSN 2473-9537 ; 2473-9529
    ISSN (online) 2473-9537
    ISSN 2473-9529
    DOI 10.1182/bloodadvances.2023012041
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    Zs.A 7153: Show issues Location:
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  5. Article ; Online: Ruxolitinib as the first post-steroid treatment for acute and chronic graft-versus-host disease.

    Algeri, Mattia / Becilli, Marco / Locatelli, Franco

    Expert review of clinical immunology

    2023  Volume 19, Issue 11, Page(s) 1299–1313

    Abstract: Introduction: Acute and chronic graft-versus-host disease (GvHD) are potentially life-threatening complications occurring after allogeneic stem cell transplantation (allo-HSCT). Although steroids represent the first-line treatment for both conditions, ... ...

    Abstract Introduction: Acute and chronic graft-versus-host disease (GvHD) are potentially life-threatening complications occurring after allogeneic stem cell transplantation (allo-HSCT). Although steroids represent the first-line treatment for both conditions, in those patients who do not adequately benefit from steroid therapy, standardized treatment algorithms are lacking. In recent years, ruxolitinib has emerged as the most promising agent for the second-line therapy of steroid-refractory (SR)-GvHD.
    Areas covered: This review will summarize the biological properties and the mechanistic aspects that justify the therapeutic role of ruxolitinib in GvHD. In addition, current treatment options for SR-GvHD will be briefly discussed. Finally, results of the most relevant clinical trials on the use of ruxolitinib for SR-GvHD will be analyzed, with a particular focus on two phase-III randomized trials in which ruxolitinib demonstrated its superiority in comparison with the best available therapy.
    Expert opinion: Ruxolitinib has considerably improved the outcome of patients with SR-acute/chronic-GvHD and should be regarded as the standard-of-care option when corticosteroids fail or cannot be tapered. Nevertheless, a number of questions still remain unanswered and significant room for improvement exists. Additional observations derived from a longer follow-up will certainly increase our expertise in the management of this powerful therapy.
    Language English
    Publishing date 2023-08-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2274260-8
    ISSN 1744-8409 ; 1744-666X
    ISSN (online) 1744-8409
    ISSN 1744-666X
    DOI 10.1080/1744666X.2023.2249230
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    Zs.A 6661: Show issues Location:
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  6. Article ; Online: Hematopoietic Stem Cell Transplantation in Thalassemia.

    Algeri, Mattia / Lodi, Mariachiara / Locatelli, Franco

    Hematology/oncology clinics of North America

    2023  Volume 37, Issue 2, Page(s) 413–432

    Abstract: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only consolidated, potentially curative treatment for patients with transfusion-dependent thalassemia major. In the past few decades, several new approaches have reduced the toxicity ... ...

    Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only consolidated, potentially curative treatment for patients with transfusion-dependent thalassemia major. In the past few decades, several new approaches have reduced the toxicity of conditioning regimens and decreased the incidence of graft-versus-host disease, improving patients' outcomes and quality of life. In addition, the progressive availability of alternative stem cell sources from unrelated or haploidentical donors or umbilical cord blood has made HSCT a feasible option for an increasing number of subjects lacking an human leukocyte antigen (HLA)-identical sibling. This review provides an overview of allogeneic hematopoietic stem cell transplantation in thalassemia, reassesses current clinical results, and discusses future perspectives.
    MeSH term(s) Humans ; Quality of Life ; Transplantation, Homologous/adverse effects ; Hematopoietic Stem Cell Transplantation/methods ; Thalassemia/therapy ; Graft vs Host Disease ; Transplantation Conditioning/methods ; Unrelated Donors
    Language English
    Publishing date 2023-03-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 93115-9
    ISSN 1558-1977 ; 0889-8588
    ISSN (online) 1558-1977
    ISSN 0889-8588
    DOI 10.1016/j.hoc.2022.12.009
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  7. Article ; Online: GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma. Reply.

    Quintarelli, Concetta / Del Bufalo, Francesca / Locatelli, Franco

    The New England journal of medicine

    2023  Volume 388, Issue 24, Page(s) 2303–2304

    Language English
    Publishing date 2023-06-14
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2305296
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    Ua VI Zs.34: Show issues Location:
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  8. Article ; Online: CAR T-Cell Therapy in Autoimmune Disease.

    De Benedetti, Fabrizio / Diomedi Camassei, Francesca / Locatelli, Franco

    The New England journal of medicine

    2023  Volume 390, Issue 17, Page(s) 1629

    MeSH term(s) Humans ; Autoimmune Diseases/therapy ; Autoimmune Diseases/immunology ; Immunotherapy, Adoptive ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; Receptors, Antigen, T-Cell/therapeutic use ; Animals
    Chemical Substances Receptors, Chimeric Antigen ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-11-16
    Publishing country United States
    Document type Journal Article ; Review ; Letter ; Comment
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMc2403705
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    Ua VI Zs.34: Show issues Location:
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  9. Article ; Online: Autologous gene therapy for hemoglobinopathies: From bench to patient's bedside.

    Locatelli, Franco / Cavazzana, Marina / Frangoul, Haydar / Fuente, Josu de la / Algeri, Mattia / Meisel, Roland

    Molecular therapy : the journal of the American Society of Gene Therapy

    2024  Volume 32, Issue 5, Page(s) 1202–1218

    Abstract: In recent years, a growing number of clinical trials have been initiated to evaluate gene therapy approaches for the treatment of patients with transfusion-dependent β-thalassemia and sickle cell disease (SCD). Therapeutic modalities being assessed in ... ...

    Abstract In recent years, a growing number of clinical trials have been initiated to evaluate gene therapy approaches for the treatment of patients with transfusion-dependent β-thalassemia and sickle cell disease (SCD). Therapeutic modalities being assessed in these trials utilize different molecular techniques, including lentiviral vectors to add functional copies of the gene encoding the hemoglobin β subunit in defective cells and CRISPR-Cas9, transcription activator-like effector protein nuclease, and zinc finger nuclease gene editing strategies to either directly address the underlying genetic cause of disease or induce fetal hemoglobin production by gene disruption. Here, we review the mechanisms of action of these various gene addition and gene editing approaches and describe the status of clinical trials designed to evaluate the potentially for these approaches to provide one-time functional cures to patients with transfusion-dependent β-thalassemia and SCD.
    MeSH term(s) Humans ; Genetic Therapy/methods ; Gene Editing/methods ; CRISPR-Cas Systems ; Hemoglobinopathies/therapy ; Hemoglobinopathies/genetics ; Genetic Vectors/genetics ; Genetic Vectors/administration & dosage ; Clinical Trials as Topic ; Anemia, Sickle Cell/therapy ; Anemia, Sickle Cell/genetics ; beta-Thalassemia/therapy ; beta-Thalassemia/genetics ; Animals ; Lentivirus/genetics
    Language English
    Publishing date 2024-03-07
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2010592-7
    ISSN 1525-0024 ; 1525-0016
    ISSN (online) 1525-0024
    ISSN 1525-0016
    DOI 10.1016/j.ymthe.2024.03.005
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  10. Article ; Online: Response to: meta-analysis on allogeneic transplant for treating pediatric patients with acute myeloid leukemia in first remission: reanalysis of primary data.

    Masetti, Riccardo / Muratore, Edoardo / Gori, Davide / Prete, Arcangelo / Locatelli, Franco

    Annals of hematology

    2023  Volume 102, Issue 8, Page(s) 2267–2270

    Language English
    Publishing date 2023-04-15
    Publishing country Germany
    Document type Meta-Analysis ; Letter
    ZDB-ID 1064950-5
    ISSN 1432-0584 ; 0939-5555 ; 0945-8077
    ISSN (online) 1432-0584
    ISSN 0939-5555 ; 0945-8077
    DOI 10.1007/s00277-023-05219-0
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    Uh III Zs.181: Show issues Location:
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