Similar efficacy outcomes with peripheral blood stem cell versus bone marrow for autologous stem cell transplantation in acute myeloid leukemia: Long-term follow-up of the EORTC-GIMEMA randomized AML-10 trial.

We report here the long-term follow-up of the only prospective randomized trial of autologous hematopoietic stem cell transplantation (auto-HSCT) with peripheral blood stem cells (APBSCT) versus auto-HSCT with bone marrow (ABMT) in acute myeloid leukemia (AML) patients in first remission (CR). We observed that among patients alive and still in CR 5 years after planned auto-HSCT, approximately 10% of the patients died in the following 10 years. This stresses the need for long-term close surveillance of AML patients after auto-HSCT.

The impact of mild behavioral impairment on the prognosis of geriatric depression: preliminary results.

Our study aimed to examine how the presence of Mild Behavioral Impairment (MBI) symptoms influenced the outcome of late-life depression (LLD). Twenty-nine elderly (≥ 60 years) depressive patients, including eleven (37.9%) with MBI, were recruited and followed-up on average for 33.

10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial.

Background: Many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes.

Methods: This open-label, randomised, controlled, phase 3 trial was conducted at 54 hospitals in nine European countries.

Impact on mental health, disease management, and socioeconomic modifications in hematological patients during the COVID-19 pandemic in Italy.

Background: Hematological patients are a highly vulnerable population with an increased risk of developing severe COVID-19 symptoms due to their immunocompromised status. COVID-19 has proven to cause serious mental health issues, such as stress, anxiety, and depression in the general population. However, data on the psycho-social impact of COVID-19 on hematological patients are lacking.

Acidic Growth Conditions Promote Epithelial-to-Mesenchymal Transition to Select More Aggressive PDAC Cell Phenotypes In Vitro.

Pancreatic Ductal Adenocarcinoma (PDAC) is characterized by an acidic microenvironment, which contributes to therapeutic failure. So far there is a lack of knowledge with respect to the role of the acidic microenvironment in the invasive process. This work aimed to study the phenotypic and genetic response of PDAC cells to acidic stress along the different stages of selection.

Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Patients with acute myeloid leukaemia (AML) positive for internal tandem duplication (ITD) mutations of FLT3 have poor outcomes. Quizartinib, an oral, highly potent, selective, type 2 FLT3 inhibitor, plus chemotherapy showed antitumour activity with an acceptable safety profile in patients with FLT3-ITD-positive newly diagnosed AML. The aim of the study was to compare the effect of quizartinib versus placebo on overall survival in patients with FLT3-ITD-positive newly diagnosed AML aged 18-75 years.

ENABLE: treatment combination including decitabine and venetoclax in acute myeloid leukemia secondary to myeloproliferative neoplasms.

The management of patients with acute myeloid leukemia (blast phase) secondary to myeloproliferative neoplasms (MPNs) is extremely challenging and the outcome dismal, with a median overall survival of about 3-6 months. Effective therapeutic approaches are lacking, especially when intensive strategies followed by allogeneic transplantation are not feasible. The combination of venetoclax and hypomethylating agents has recently been established as standard for newly diagnosed, unfit patients with acute myeloid leukemia, but the application of this therapeutic modality has not been tested prospectively in the specific context of blast-phase MPNs.

Pharmacotherapy for bipolar disorder in adults with high-functioning autism.

Introduction: The association between high-functioning autism (HFA) and bipolar disorder (BD) in adult subjects has been confirmed by a growing number of studies. However, identifying and treating BD in this population is a clinical challenge and requires careful assessment and adequate knowledge of both disorders.

Areas Covered: This review aims to provide a clinical presentation of mood episodes in HFA individuals, and an update on the pharmacotherapy of BD in these individuals, sharing with the reader expert opinion on the current state of the art and future perspectives.

A 3-Dimensional Evaluation of Bone Density in Alveolar Cleft Grafting Methods: Bone Substitutes Versus Autologous Bone.

Introduction: Secondary alveolar cleft repair using autologous bone graft is currently the gold standard in treating residual alveolar clefts. Despite its effectiveness, this technique is still burdened by several withdrawals, mostly related to donor site morbidity. To decrease disadvantages for patients, numerous attempts in the literature regarding bone substitutes have been described.

Bipolar Disorder and Manic-Like Symptoms in Alzheimer's, Vascular and Frontotemporal Dementia: A Systematic Review.

Background: An increased risk of manic episodes has been reported in patients with neurodegenerative disorders, but the clinical features of bipolar disorder (BD) in different subtypes of dementia have not been thoroughly investigated.

Objectives: The main aim of this study is to systematically review clinical and therapeutic evidence about manic syndromes in patients with Alzheimer's disease (AD), vascular dementia (VaD), and frontotemporal dementia (FTD). Since manic-mixed episodes have been associated to negative outcomes in patients with dementia and often require medical intervention, we also critically summarized selected studies with relevance for the treatment of mania in patients with cognitive decline.

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol.

IDH1/2 mutations are common in acute myeloid leukemia (AML) and represent a therapeutic target. The GIMEMA AML1516 observational protocol was designed to study the prevalence of IDH1/2 mutations and associations with clinico-biological parameters in a cohort of Italian AML patients. We analyzed a cohort of 284 AML consecutive patients at diagnosis, 139 females and 145 males, of a median age of 65 years (range: 19−86).

Obsessive-Compulsive and Depressive Symptoms in Professional Tennis Players.

Objective: A moderate sport activity is considered beneficial for both physical and mental health. On the contrary, different studies have shown that professional players may be more vulnerable to suffer from psychological and/or psychiatric disorders. Given the limited information available, the present study aimed to investigate the possible presence of depressive and obsessive-compulsive symptoms or disorders in a group of professional tennis players.

Molecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results.

In acute myeloid leukemia (AML) internal tandem duplications of the FLT3 gene (FLT3-ITD) are associated with poor prognosis. Retrospectively, we investigated the prognostic and predictive impact of FLT3-ITD insertion site (IS) in 452 patients randomized within the RATIFY trial, which evaluated midostaurin additionally to intensive chemotherapy. Next-generation sequencing identified 908 ITDs, with 643 IS in the juxtamembrane domain (JMD) and 265 IS in the tyrosine kinase domain-1 (TKD1).

Treatment adherence and tolerability of immediate- and prolonged-release lithium formulations in a sample of bipolar patients: a prospective naturalistic study.

The aim of this study was to compare treatment adherence and tolerability of different lithium formulations in 70 bipolar patients receiving lithium therapy for the first time. During the 1-year follow-up, information was collected regarding patient's clinical course, therapeutic adherence, side effects of the treatment and serum levels of lithium, creatinine and thyroid-stimulating hormone. At baseline, 30 patients (43%) were on prolonged-release lithium formulations and 40 (57%) on immediate-release formulations.

AMELIORATE: early intensification in -mutated acute myeloid leukemia based on peripheral blast clearance - MYNERVA-GIMEMA AML1919 trial.

AMELIORATE is a Phase III, randomized trial aiming to personalize treatment intensity in -mutated acute myeloid leukemia. The current study provides an early appraisal of chemosensitivity based on peripheral blasts clearance, as assessed by multiparameter flow cytometry, from baseline to day 4 of induction. This biomarker was previously demonstrated to predict complete remission achievement and measurable residual disease status.

Midostaurin reduces relapse in FLT3-mutant acute myeloid leukemia: the Alliance CALGB 10603/RATIFY trial.

The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy.

Survival Improvement over Time of 960 s-AML Patients Included in 13 EORTC-GIMEMA-HOVON Trials.

We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively.

Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial.

The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations.

Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long-term follow up of a phase III study.

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m ), mitoxantrone (MXR, 12 mg/m ), or idarubicin (IDA, 10 mg/m ) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered.

Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia.

Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (≥0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status.

Chemotherapy-Induced Tumor Cell Death at the Crossroads Between Immunogenicity and Immunotolerance: Focus on Acute Myeloid Leukemia.

In solid tumors and hematological malignancies, including acute myeloid leukemia, some chemotherapeutic agents, such as anthracyclines, have proven to activate an immune response via dendritic cell-based cross-priming of anti-tumor T lymphocytes. This process, known as immunogenic cell death, is characterized by a variety of tumor cell modifications, i.e.

GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia.

We designed a trial in which postremission therapy of young patients with de novo acute myeloid leukemia (AML) was decided combining cytogenetics/genetics and postconsolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (AlloSCT). Intermediate-risk patients (IR) were to receive AuSCT or AlloSCT depending on the postconsolidation levels of MRD.