0000000000276060
AUTHOR
Giovanni Martinelli
BCR-ABL Derived Peptide Vaccine in Chronic Myeloid Leukemia Patients with Molecular Minimal Residual Disease During Imatinib: Interim Analysis of a Phase 2 Multicenter GIMEMA CML Working Party Trial.
Abstract Abstract 648 Introduction: Imatinib (IM) 400mg daily is the standard treatment for chronic myeloid leukemia (CML) patients and a complete cytogenetic response (CCyR) is achieved in the majority of patients within one year of treatment. In addition, a considerable number of patients reach a major molecular response (i.e BCR-ABL/ABL ratio <0.1%) but BCR-ABL transcript is still measurable in most of treated patients revealing the persistence of a minimal residual disease (MRD). In a previous small pilot study, vaccinations with p210 b3a2-derived fusion peptides in IM treated CML patients appeared to induce both a peptide specific immune response and a reduction of residual disease …
Significance of earthquake-related anomalies in fluids of Val D'Agri (southern Italy)
Geochemical investigations carried out at the Campano–Lucano Apennine (Southern Italy) revealed the presence of fluids composed of a mixing between components of shallow and deep origin, where mantle-derived helium is also detectable. For the gas phase, the deep component is represented by both CH4 and CO2-rich gases, while the shallow one is N2-dominated. Coinciding with the 3 April 1996 ML=4.9 earthquake, the CH4-rich component mixed with the shallow, N2-dominated one at the Tramutola well (Val d’Agri), displaying wide variations in mixing proportions. In contrast, no significant modifications occurred in relation to the 1998 ML=5.5 event. According to the collected data, an earthquake-re…
Differences among young adults, adults and elderly chronic myeloid leukemia patients
Abstract BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old)…
Coseismic geochemical variations in some gas emissions of Umbria region (Central Italy)
Abstract Coseismic geochemical variations have been detected in some gaseous vents and natural springs during the last seismic crisis occurred in Umbria region (Central Apennines), that started on September 26th, 1997 with several moderate earthquakes (up to M1 5.8). The results of chemical analyses performed on both gas and water samples taken at a weekly rate, combined with analyses on continuous gas flow rate nearby San Faustino site, suggest that the variations can be interpreted as possible consequence of the crustal permeability changes induced by earthquake shaking.
Targeting a Specific Glycosylated Epitope of CD43 with a New Humanized Monoclonal Antibody for the Treatment of Pediatric and Adult T-Cell Acute Lymphoblastic Leukemia (T-ALL)
Abstract Introduction: T-cell acute lymphoblastic leukemia (T-ALL) accounts for about 20% of pediatric and adult ALL cases. Despite the use of intensive chemotherapy protocols, 25% of children and 50% of adult patients fail to respond or relapse. The 3-years prognosis for these patients is poor and novel treatment options are needed. The targeting of tumor-associated antigens by monoclonal antibodies (mAb) is among the most investigated immune-therapeutic strategies. Accordingly, we developed a new humanized mAb (hUMG1), directed against a heavy glycosylated epitope of CD43 which presents a high reactivity against T-ALL cells. Here we investigated the pre-clinical therapeutic activity and t…
Systemic mastocytosis. A GIMEMA multicenter survey
Abstract To evaluate clinical and biological features, treatments and outcome of patients(pts) with Systemic Mastocytosis(SM). A retrospective study (1995–2006) about pts with SM admitted in 14 Italian hematology divisions in tertiary cares or university hospitals. 30 cases of SM were collected(median age 62 y.o.; M/F 14/16) and classified according to the WHO criteria: Mast Cell Leukemia in 14 pts, Aggressive SM in 12 and Indolent in 3; the remaining one had SM with associated clonal non-mast cell-lineage hematologic disease. Skin was the principal extramedullary organ involved (19 pts) followed by spleen(15), liver(13), and cardiovascular system(12). Molecular biology studies were perform…
Release of IFNγ by Acute Myeloid Leukemia Cells Remodels Bone Marrow Immune Microenvironment by Inducing Regulatory T Cells
Abstract Purpose: The stromal and immune bone marrow (BM) landscape is emerging as a crucial determinant for acute myeloid leukemia (AML). Regulatory T cells (Treg) are enriched in the AML microenvironment, but the underlying mechanisms are poorly elucidated. Here, we addressed the effect of IFNγ released by AML cells in BM Treg induction and its impact on AML prognosis. Experimental Design: BM aspirates from patients with AML were subdivided according to IFNG expression. Gene expression profiles in INFγhigh and IFNγlow samples were compared by microarray and NanoString analysis and used to compute a prognostic index. The IFNγ release effect on the BM microenvironment was investigated in me…
Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial
Background Patients with relapsed or refractory FLT3 internal tandem duplication (FLT3-ITD)-positive acute myeloid leukaemia have a poor prognosis, including high frequency of relapse, poorer response to salvage therapy, and shorter overall survival than those with FLT3 wild-type disease. We aimed to assess whether single-agent quizartinib, an oral, highly potent and selective type II FLT3 inhibitor, improves overall survival versus salvage chemotherapy. Methods QuANTUM-R is a randomised, controlled, phase 3 trial done at 152 hospitals and cancer centres in 19 countries. Eligible patients aged 18 years or older with ECOG performance status 0-2 with relapsed or refractory (duration of first …
Della Libraria Vaticana ragionamenti / di Mutio Pansa ; Diuisi in quattro parti ... ; Con l'Agiunta degli Alfabeti de Lingue straniere, e con alcuni Discorsi in fine de Libri, e della Stampa Vaticana, & di molte altre Librarie ... in Roma ...
Sig. *4, A-Yy4 Els grav. xil. son de la biblioteca en p. 126 i de diferents alfabets. - Frisos, filets i altres ornaments tip. - Capitals grav. Text amb postil·les marginals. - Registre. - Reclams
Prevention of venous thromboembolic events occurring in myeloma patients treated with second-generation novel agents
Thrombosis and neoplasms are strictly linked, and the diagnosis of a malignancy is a relevant risk factor for venous thromboembolism (VTE). In particular, between gammopathies, the VTE risk is known to be increased in both monoclonal gammopathy of uncertain significance and in multiple myeloma, with a 3- and 9-fold increase respectively, when compared to the general population. The risk appears to be further increased in patients treated with immunomodulating drugs, such as thalidomide, especially when in combination with dexamethasone or conventional cytotoxic chemotherapies, and lenalidomide. In 2008 the International Myeloma Working Group put out thrombosis prophylaxis recommendations fo…
Efficacy and Safety of Single-Agent Quizartinib (Q), a Potent and Selective FLT3 Inhibitor (FLT3i), in Patients (pts) with FLT3-Internal Tandem Duplication (FLT3-ITD)-Mutated Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) Enrolled in the Global, Phase 3, Randomized Controlled Quantum-R Trial
Abstract Introduction: FLT3-ITD mutations are among the most common molecular abnormalities in AML, occurring in ≈ 25% of pts. These driver mutations are associated with high leukemic burden and poor prognosis, eg, high risk of relapse, decreased response to salvage therapy, and shorter overall survival (OS). Pts with R/R FLT3-ITD AML have a worse prognosis and represent a population with high unmet medical need. Q is a once-daily, oral, highly potent and selective FLT3i shown in phase 2 trials to have promising single-agent antileukemic activity and a manageable safety profile. QuANTUM-R was the first global, phase 3, randomized controlled trial (NCT02039726) to show that an FLT3i prolonge…
Efficacy and safety of yttrium 90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem cell transplantation.
A prospective, multicenter, nonrandomized phase 2 trial was conducted to evaluate the efficacy and safety of a single dose of yttrium-90 (90Y) ibritumomab tiuxetan in elderly patients in first relapsed or primary refractory diffuse large B-cell lymphoma (DLBCL) ineligible for stem-cell transplantation. Patients had been previously treated with chemotherapy (group A, n = 76) or chemotherapy plus rituximab (group B, n = 28). Patients in group A were further divided into patients in whom induction therapy had failed (stratum AI, n = 33) and patients who had relapsed after achieving complete response (CR; stratum AII, n = 43). The overall response rate (ORR) was 52% and 53% in strata AI and AII…
Della Libraria Vaticana ragionamenti
Sig. *4, A-Yy4 Els grav. xil. son de la biblioteca en p. 126 i de diferents alfabets. - Frisos, filets i altres ornaments tip. - Capitals grav Text amb postil·les marginals. - Registre. - Reclams
Quizartinib in FLT3-ITD-Mutated Relapsed/Refractory Acute Myeloid Leukemia: QuANTUM-R Trial Results
Abstract Background FLT3-ITD mutations occur in about 25% of patients (pts) with acute myeloid leukemia (AML) and are associated with poor outcomes. Pts with relapsed/refractory (R/R) FLT3-ITD AML have worse prognosis and high unmet medical need. Quizartinib (Q) is a potent and selective FLT3i with promising activity and a manageable safety profile. QuANTUM-R was a global, phase 3, randomized trial of Q vs chemotherapy (SC) in pts with R/R FLT3-ITD AML (NCT02039726). Methods Pts with R/R FLT3-ITD AML w/wo hematopoietic stem cell transplant (HSCT) were randomized to receive Q or a preselected investigator choice SC: low-dose cytarabine; mitoxantrone, etoposide, and intermediate-dose cytarabi…
Clinical and biological data on the use of hydroxychloroquine against SARS-CoV-2 could support the role of the NLRP3 inflammasome in the pathogenesis of respiratory disease
The use of hydroxychloroquine (HCL) has been very common in countries with a rapid spread of coronavirus disease 2019 (COVID-19), although controversial and the subject of heated scientific discussions with implications for the whole society. This article is protected by copyright. All rights reserved.
Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol
Simple Summary IDH1/2 mutations are a common event in acute myeloid leukemia (AML) and represent a therapeutic target. We designed the GIMEMA AML1516 observational protocol to examine the prevalence of IDH1/2 mutations and the associations between IDH mutations and clinico-biological parameters in a cohort of Italian patients affected by AML. By analyzing 284 consecutive adult AML patients, we confirmed that IDH1 and IDH2 mutations are frequently detected-14% and 18%, respectively-at diagnosis. IDH1/2 mutations were significantly associated with an inferior performance status and non-complex karyotype when compared to IDH1/2-WT. With regards to the outcome, in the subset of IDH1/2-mutated p…
Treatment of Lenalidomide Exposed or Refractory Multiple Myeloma: Network Meta-Analysis of Lenalidomide-Sparing Regimens.
Over the past 10 years, the treatment of multiple myeloma (MM) dramatically changed due to the introduction of a number of new agents and combination regimens both in the frontline and in the relapsed/refractory setting. Currently, at least 11 classes of therapeutic agents, including steroids, alkylators (melphalan and cyclophosphamide), proteasome inhibitors (PI: bortezomib, carfilzomib, ixazomib), immunomodulatory agents (thalidomide, lenalidomide, pomalidomide), monoclonal antibodies (mAbs: elotuzumab, daratumumab), HDAC-inhibitors (panobinostat), BCL2 inhibitors (venetoclax), selective inhibitors of nuclear export (selinexor), drug-conjugated mAbs (belantamab mafodotin), bispecific agen…
Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia
BackgroundT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a poor cure rate for relapsed/resistant patients. Due to the lack of T-cell restricted targetable antigens, effective immune-therapeutics are not presently available and the treatment of chemo-refractory T-ALL is still an unmet clinical need. To develop novel immune-therapy for T-ALL, we generated an afucosylated monoclonal antibody (mAb) (ahuUMG1) and two different bispecific T-cell engagers (BTCEs) against UMG1, a unique CD43-epitope highly and selectively expressed by T-ALL cells from pediatric and adult patients.MethodsUMG1 expression was assessed by immunohistochemistry (IHC) on a wide panel of normal t…
Post-transplant consolidation based on combination of lenalidomide and proteasome inhibitors in multiple myeloma
Multiple myeloma (MM) is a hematological malignancy due to uncontrolled proliferation of neoplastic plasma cells in the bone marrow, associated to chromosomal instability and cytogenetic abnormalities, which could have an impact on prognosis. Response to treatment and survival of newly diagnosed myeloma patients is heterogeneous, with median overall survival ranging from two to more than ten years, due to clinical and biological factors. To warrant long-term control of disease, several strategies have been proposed in the last years, including short-term high-dose of treatment, named as consolidation, before maintenance. This review will discuss the role of consolidation in the current myel…