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Article: Editorial: The Elephant in the Room: AML Relapse After Allogeneic Hematopoietic Cell Transplantation.

Battipaglia, Giorgia / Saraceni, Francesco / Malard, Florent

2022 Volume 12, Page(s) 863800

Language	English
Publishing date	2022-03-21
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2022.863800
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Article ; Online: BH3 mimetics in relapsed and refractory adult acute lymphoblastic leukemia: a Campus ALL real-life study.

Malfona, Francesco / Tanasi, Ilaria / Piccini, Matteo / Papayannidis, Cristina / Federico, Vincenzo / Mancini, Valentina / Roncoroni, Elisa / Todisco, Elisabetta / Bianchi, Simona / Ciotti, Giulia / Chiusolo, Patrizia / Gentile, Massimo / Gianfelici, Valentina / Giglio, Fabio / Malagola, Michele / Mulé, Antonino / Saraceni, Francesco / Vetro, Calogero / Zallio, Francesco /

Cappelli, Luca Vincenzo / Pizzolo, Giovanni / Foà, Robin / Bonifacio, Massimiliano / Chiaretti, Sabina

Haematologica

2024 Volume 109, Issue 3, Page(s) 988–993

MeSH term(s)	Adult ; Humans ; Acute Disease ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
Language	English
Publishing date	2024-03-01
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.283684
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Article: Overcoming Resistance: FLT3 Inhibitors Past, Present, Future and the Challenge of Cure.

Capelli, Debora / Menotti, Diego / Fiorentini, Alessandro / Saraceni, Francesco / Olivieri, Attilio

Cancers

2022 Volume 14, Issue 17

Abstract: FLT3 ITD and TKD mutations occur in 20% and 10% of Acute Myeloid Leukemia (AML), respectively, and they represent the target of the first approved anti-leukemic therapies in the 2000s. Type I and type II FLT3 inhibitors (FLT3i) are active against FLT3 ... ...

Abstract	FLT3 ITD and TKD mutations occur in 20% and 10% of Acute Myeloid Leukemia (AML), respectively, and they represent the target of the first approved anti-leukemic therapies in the 2000s. Type I and type II FLT3 inhibitors (FLT3i) are active against FLT3 TKD/ITD and FLT3 ITD mutations alone respectively, but they still fail remissions in 30-40% of patients due to primary and secondary mechanisms of resistance, with variable relapse rate of 30-50%, influenced by NPM status and FLT3 allelic ratio. Mechanisms of resistance to FLT3i have recently been analyzed through NGS and single cell assays that have identified and elucidated the polyclonal nature of relapse in clinical and preclinical studies, summarized here. Knowledge of tumor escape pathways has helped in the identification of new targeted drugs to overcome resistance. Immunotherapy and combination or sequential use of BCL2 inhibitors and experimental drugs including aurora kinases, menin and JAK2 inhibitors will be the goal of present and future clinical trials, especially in patients with FLT3-mutated (FLT3mut) AML who are not eligible for allogeneic transplantation.
Language	English
Publishing date	2022-09-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14174315
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Article ; Online: Allogeneic hematopoietic cell transplantation for VEXAS syndrome: results of a multicenter study of the EBMT.

Gurnari, Carmelo / Koster, Linda / Baaij, Laurien / Heiblig, Mael / Yakoub-Agha, Ibrahim / Collin, Matthew / Passweg, Jakob / Bulabois, Claude E / Khan, Anjum / Loschi, Michael / Carnevale-Schianca, Fabrizio / Crisà, Elena / Caravelli, Daniela / Kuball, Jürgen / Saraceni, Francesco / Olivieri, Attilio / Rambaldi, Alessandro / Kulasekararaj, Austin G / Hayden, Patrick J /

Badoglio, Manuela / Onida, Francesco / Scheid, Christof / Franceschini, Franco / Mekinian, Arsène / Savic, Sinisa / Voso, Maria Teresa / Drozd-Sokolowska, Joanna / Snowden, John A / Raj, Kavita / Alexander, Tobias / Robin, Marie / Greco, Raffaella / McLornan, Donal P

Blood advances

2024 Volume 8, Issue 6, Page(s) 1444–1448

MeSH term(s)	Hematopoietic Stem Cell Transplantation/methods ; Myelodysplastic Syndromes ; Skin Diseases, Genetic ; Transplantation, Homologous ; Humans
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Multicenter Study ; Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023012478
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Article ; Online: Impact of inotuzumab ozogamicin on outcome in relapsed or refractory acute B-cell lymphoblastic leukemia patients prior to allogeneic hematopoietic stem cell transplantation and risk of sinusoidal obstruction syndrome/venous occlusive disease.

Kayser, Sabine / Sartor, Chiara / Giglio, Fabio / Bruno, Alessandro / Webster, Jonathan / Chiusolo, Patrizia / Saraceni, Francesco / Guerzoni, Selene / Pochintesta, Lara / Borlenghi, Erika / Marconi, Giovanni / Zacheo, Irene / Cerrano, Marco / Salutari, Prassede / Restuccia, Francesco / Abbenante, Mariachiara / Levis, Mark J / Schlenk, Richard F / Papayannidis, Cristina

Haematologica

2024 Volume 109, Issue 5, Page(s) 1385–1392

Abstract: We evaluated 58 patients with relapsed or refractory (r/r) acute B-lymphoblastic leukemia (B-ALL; median age 42.5 years; range, 16-69 years), treated with inotuzumab ozogamicin (INO) between 2016-2022 and who received an allogeneic hematopoietic stem ... ...

Abstract	We evaluated 58 patients with relapsed or refractory (r/r) acute B-lymphoblastic leukemia (B-ALL; median age 42.5 years; range, 16-69 years), treated with inotuzumab ozogamicin (INO) between 2016-2022 and who received an allogeneic hematopoietic stem cell transplantation (allo-HCT) consecutively. Forty-seven (81%) of the 58 patients were heavily pretreated receiving intensive chemotherapy +/- tyrosine kinase inhibitor, blinatumomab in 24 (41%) and allo-HCT at first-line in 11 (19%) patients. Complete remission rate prior to allo-HCT was 84%. Median follow-up was 30.5 months and median overall survival (OS) measured from start of INO was 11.2 months. One- and 2-year OS rates were 50% (95% confidence interval [CI]: 38.4-56.1) and 36.7% (95% CI: 25.5-52.9), respectively. Sinusoidal obstruction syndrome/venous occlusive disease (SOS/ VOD) after allo-HCT occurred in 17 (29%) patients. Of those, nine (53%) patients died due to SOS/VOD and multi-organ failure. Two had received >2 INO cycles (3 cycles, 5 cycles, N=1, each), all others ≤2 INO cycles prior to allo-HCT. Logistic regression analysis revealed conditioning with double alkylators (P=0.038) and allo-HCT during first-line therapy (P=0.050) as significant risk factors for SOS/VOD and in trend allo-HCT ≤60 days from last INO application (P=0.07), whereas number of INO cycles before allo-HCT and time between last INO application and allo-HCT were not significant. Relapse/progressive disease occurred in 20 (34%) patients. Of those, five (25%) patients are still alive, whereas 15 succumbed of their disease. Treatment with INO seems to be an effective approach with successful bridge-to-transplant. However, risk of SOS/VOD is high, necessitating continuous monitoring and recognition of SOS/VOD risk factors.
MeSH term(s)	Humans ; Inotuzumab Ozogamicin/therapeutic use ; Hematopoietic Stem Cell Transplantation/adverse effects ; Adult ; Middle Aged ; Hepatic Veno-Occlusive Disease/etiology ; Hepatic Veno-Occlusive Disease/diagnosis ; Hepatic Veno-Occlusive Disease/chemically induced ; Male ; Female ; Adolescent ; Aged ; Young Adult ; Transplantation, Homologous ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/mortality ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Treatment Outcome ; Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Agents, Immunological/adverse effects ; Antineoplastic Agents, Immunological/administration & dosage ; Recurrence ; Transplantation Conditioning/methods ; Transplantation Conditioning/adverse effects
Chemical Substances	Inotuzumab Ozogamicin (P93RUU11P7) ; Antineoplastic Agents, Immunological
Language	English
Publishing date	2024-05-01
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.284310
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Article ; Online: Treatment of Adult Patients with Relapsed/Refractory B-Cell Philadelphia-Negative Acute Lymphoblastic Leukemia.

Maffini, Enrico / Saraceni, Francesco / Lanza, Francesco

Clinical hematology international

2019 Volume 1, Issue 2, Page(s) 85–93

Abstract: The majority of adult patients affected by B-cell acute lymphoblastic leukemia (B-ALL) will relapse after an initial response, while approximately 20% will display primary resistant disease. Patients suffering from relapsed/refractory B-ALL have a very ... ...

Abstract	The majority of adult patients affected by B-cell acute lymphoblastic leukemia (B-ALL) will relapse after an initial response, while approximately 20% will display primary resistant disease. Patients suffering from relapsed/refractory B-ALL have a very poor outcome. Allogeneic hematopoietic cell transplantation (HCT) still represents the only curative approach, but is not so frequently feasible, because of patient's fitness, donor availability, and the ability to achieve a remission prior to HCT. The estimated remission rates with conventional cytotoxic agents are around 30%, but they are short-lived. These disappointing results led to the introduction of new immunologic-based treatments-blinatumomab and inotuzumab. They produced a substantial improvement in terms of response rates, with the ability, in most cases, to induce a minimal residual disease (MRD)-negative status. Similarly, T cells engineered to express a CD19-specific chimeric antigen receptor (CAR-T) have yielded sensational results among patients with relapsed/refractory B-ALL, with unexpectedly high MRD-negative complete remissions rates. However, the first studies looking at long-term outcomes after CAR-T infusions told us that a significant fraction of such responses are not durable, and may benefit from a consolidation approach such as an allogeneic HCT.
Language	English
Publishing date	2019-05-11
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2590-0048
ISSN (online)	2590-0048
DOI	10.2991/chi.d.190503.002
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Article ; Online: Treatment of Adult Patients with Relapsed/Refractory B-Cell Philadelphia-Negative Acute Lymphoblastic Leukemia

Enrico Maffini / Francesco Saraceni / Francesco Lanza

Clinical Hematology International, Vol 1, Iss

2019 Volume 2

Abstract	The majority of adult patients affected by B-cell acute lymphoblastic leukemia (B-ALL) will relapse after an initial response, while approximately 20% will display primary resistant disease. Patients suffering from relapsed/refractory B-ALL have a very poor outcome. Allogeneic hematopoietic cell transplantation (HCT) still represents the only curative approach, but is not so frequently feasible, because of patient's fitness, donor availability, and the ability to achieve a remission prior to HCT. The estimated remission rates with conventional cytotoxic agents are around 30%, but they are short-lived. These disappointing results led to the introduction of new immunologic-based treatments—blinatumomab and inotuzumab. They produced a substantial improvement in terms of response rates, with the ability, in most cases, to induce a minimal residual disease (MRD)-negative status. Similarly, T cells engineered to express a CD19-specific chimeric antigen receptor (CAR-T) have yielded sensational results among patients with relapsed/refractory B-ALL, with unexpectedly high MRD-negative complete remissions rates. However, the first studies looking at long-term outcomes after CAR-T infusions told us that a significant fraction of such responses are not durable, and may benefit from a consolidation approach such as an allogeneic HCT.
Keywords	Acute lymphoblastic leukemia ; Inotuzumab ; Blinatumomab ; Allogeneic hematopoietic cell transplantation ; Medicine ; R
Subject code	610
Language	English
Publishing date	2019-05-01T00:00:00Z
Publisher	Atlantis Press
Document type	Article ; Online
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Article ; Online: Autologous Stem Cell Transplantation in Multiple Myeloma: Where Are We and Where Do We Want to Go?

Morè, Sonia / Corvatta, Laura / Manieri, Valentina Maria / Saraceni, Francesco / Scortechini, Ilaria / Mancini, Giorgia / Fiorentini, Alessandro / Olivieri, Attilio / Offidani, Massimo

Cells

2022 Volume 11, Issue 4

Abstract: The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for ... ...

Abstract	The introduction of high-dose therapy in the 1990s as well as the development of drugs such as thalidomide, lenalidomide, and bortezomib in the 2000s led to an impressive improvement in outcome of patients with multiple myeloma (MM) eligible for autologous stem cell transplantation (ASCT). Clinical trials conducted in the first ten years of the twenty-first century established as standard therapy for these patients a therapeutic approach including induction, single or double ASCT, consolidation, and maintenance therapy. More recently, incorporating second-generation proteasome inhibitors carfilzomib and monoclonal antibody daratumumab into each phase of treatment significantly improved the efficacy of ASCT in terms of measurable residual disease (MRD) negativity, Progression Free Survival (PFS), and Overall Survival (OS). The availability of techniques such as multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for MRD assessment allowed the design of MRD-based response-adjusted trials that will define, in particular, the role of consolidation and maintenance therapies. In this review, we will provide an overview of the most recent evidence and the future prospects of ASCT in MM patients.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Dexamethasone ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Multiple Myeloma/drug therapy ; Transplantation, Autologous
Chemical Substances	Dexamethasone (7S5I7G3JQL)
Language	English
Publishing date	2022-02-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11040606
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Article ; Online: The Time Has Come for Targeted Therapies for AML: Lights and Shadows.

Fiorentini, Alessandro / Capelli, Debora / Saraceni, Francesco / Menotti, Diego / Poloni, Antonella / Olivieri, Attilio

Oncology and therapy

2020 Volume 8, Issue 1, Page(s) 13–32

Abstract: Acute myeloid leukemia (AML) is a complex disease characterized by genetic and clinical heterogeneity and high mortality. After 40 years during which the standard of care for patients evolved very little, the therapeutic landscape has recently seen rapid ...

Abstract	Acute myeloid leukemia (AML) is a complex disease characterized by genetic and clinical heterogeneity and high mortality. After 40 years during which the standard of care for patients evolved very little, the therapeutic landscape has recently seen rapid changes, with the approval of eight new drugs by the Food and Drug Administration (FDA) within the last 2 years, providing new opportunities, as well as new challenges, for treating clinicians. These therapies include FLT3 inhibitors midostaurin and gilteritinib, CPX-351 (liposomal cytarabine and daunorubicin), gemtuzumab ozogamicin (GO, anti-CD33 monoclonal antibody conjugated with calicheamicin), IDH1/IDH2 inhibitors ivosidenib and enasidenib, Hedgehog inhibitor glasdegib, and BCL-2 inhibitor venetoclax. In this review, we summarize currently available data on these new drugs and discuss the rapidly evolving therapeutic armamentarium for AML, focusing on targeted therapies.
Language	English
Publishing date	2020-01-24
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2848647-X
ISSN	2366-1089 ; 2366-1070
ISSN (online)	2366-1089
ISSN	2366-1070
DOI	10.1007/s40487-019-00108-x
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Article ; Online: Design and Characterization of Myristoylated and Non-Myristoylated Peptides Effective against

Bugli, Francesca / Massaro, Federica / Buonocore, Francesco / Saraceni, Paolo Roberto / Borocci, Stefano / Ceccacci, Francesca / Bombelli, Cecilia / Di Vito, Maura / Marchitiello, Rosalba / Mariotti, Melinda / Torelli, Riccardo / Sanguinetti, Maurizio / Porcelli, Fernando

International journal of molecular sciences

2022 Volume 23, Issue 4

Abstract: The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually ... ...

Abstract	The increasing resistance of fungi to antibiotics is a severe challenge in public health, and newly effective drugs are required. Promising potential medications are lipopeptides, linear antimicrobial peptides (AMPs) conjugated to a lipid tail, usually at the N-terminus. In this paper, we investigated the in vitro and in vivo antifungal activity of three short myristoylated and non-myristoylated peptides derived from a mutant of the AMP
MeSH term(s)	Animals ; Antifungal Agents/chemistry ; Antifungal Agents/pharmacology ; Biofilms ; Candida ; Candida albicans ; Humans ; Larva ; Lipopeptides/pharmacology ; Mammals ; Microbial Sensitivity Tests
Chemical Substances	Antifungal Agents ; Lipopeptides
Language	English
Publishing date	2022-02-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23042164
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