Impact of Pre-Treatment Comorbidity Burden on Survival in Patients Receiving Venetoclax Plus Hypomethylating Agents.

Expectation of survival of patients receiving HMA + VEN is influenced by pre-treatment comorbidity burden.

Tyrosine kinase inhibitor discontinuation in non-allografted Philadelphia-positive acute lymphoblastic leukemia patients: a Campus ALL real-life study.

Not available.

Efficacy of Midostaurin Combined With Intensive Chemotherapy in Core Binding Factor Leukemia: A Phase II Clinical Trial.

Samples from 34 adult patients newly diagnosed with core binding factor leukemia (CBFL) were collected both at the time of diagnosis and at relapse and were centrally analyzed. Eligible patients received either standard induction CT known as "3 + 7" or an equivalent regimen, according to the recruiting center's policy. Patients who achieved CR or CRi received 3 courses of high-dose ARA-C (Cytarabine) 3000 mg/m every 12 h on days 1, 3, and 5, along with midostaurin at the dose of 50 mg b.

Identification of Novel Potential Predisposing Variants in Familial Acute Myeloid Leukemia.

Background: Myeloid neoplasms, including acute myeloid leukemia, have been traditionally among the less investigated cancer types concerning germline predisposition. Indeed, myeloid neoplasms with germline predisposition are challenging to identify because often display similar clinical and morphological characteristics of sporadic cases and have similar age at diagnosis. However, a misidentifications of familiarity in myeloid neoplasms have a critical impact on clinical management both for the carriers and their relatives.

Literature review and expert opinion on the treatment of high-risk acute myeloid leukemia in patients who are eligible for intensive chemotherapy.

In patients with Acute Myeloid Leukemia (AML), the assessment of disease risk plays a central role in the era of personalized medicine. Indeed, integrating baseline clinical and biological features on a case-by-case basis is not only essential to select which treatment would likely result in a higher probability of achieving complete remission, but also to dynamically customize any subsequent therapeutic intervention. For young high-risk patients with low comorbidities burden and in good general conditions (also called "fit" patients), intensive chemotherapy followed by allogeneic stem cell transplantation still represents the backbone of any therapeutic program.

Pivekimab sunirine (IMGN632), a novel CD123-targeting antibody-drug conjugate, in relapsed or refractory acute myeloid leukaemia: a phase 1/2 study.

Background: Pivekimab sunirine (IMGN632) is a first-in-class antibody-drug conjugate comprising a high-affinity CD123 antibody, cleavable linker, and novel indolinobenzodiazepine pseudodimer payload. CD123 is overexpressed in several haematological malignancies, including acute myeloid leukaemia. We present clinical data on pivekimab sunirine in relapsed or refractory acute myeloid leukaemia.

Aberrant cortex contractions impact mammalian oocyte quality.

The cortex controls cell shape. In mouse oocytes, the cortex thickens in an Arp2/3-complex-dependent manner, ensuring chromosome positioning and segregation. Surprisingly, we identify that mouse oocytes lacking the Arp2/3 complex undergo cortical actin remodeling upon division, followed by cortical contractions that are unprecedented in mammalian oocytes.

Adapting the Fitness Criteria for Non-Intensive Treatments in Older Patients with Acute Myeloid Leukemia to the Use of Venetoclax-Hypomethylating Agents Combination-Practical Considerations from the Real-Life Experience of the Hematologists of the Rete Ematologica Lombarda.

A retrospective survey was conducted in hematologic centres of the Rete Ematologica Lombarda (REL) on 529 older AML patients seen between 2020-2022. Compared to 2008-2016, the use of intensive chemotherapy (ICT) decreased from 40% to 18.1% and of hypomethylating agents (HMAs) from 19.

Improved efficiency of daratumumab treatment of multiple myeloma adopting the subcutaneous route: A micro-costing analysis in three Italian hematology centers.

Background: Daratumumab is a humanized monoclonal antibody approved for the treatment of adult patients with newly diagnosed or relapsed/refractory multiple myeloma (RRMM). Subcutaneous (SC) formulation proved to be non-inferior in comparison with intravenous (IV) administration route. This study aimed at assessing the economic and time impact associated with the use of SC versus IV daratumumab in patients with RRMM from the perspective of the hematology center.

Spatial communication systems across languages reflect universal action constraints.

The extent to which languages share properties reflecting the non-linguistic constraints of the speakers who speak them is key to the debate regarding the relationship between language and cognition. A critical case is spatial communication, where it has been argued that semantic universals should exist, if anywhere. Here, using an experimental paradigm able to separate variation within a language from variation between languages, we tested the use of spatial demonstratives-the most fundamental and frequent spatial terms across languages.

Multicenter retrospective analysis of clinical outcome of adult patients with mixed-phenotype acute leukemia treated with acute myeloid leukemia-like or acute lymphoblastic leukemia-like chemotherapy and impact of allogeneic stem cell transplantation: a Campus ALL study.

Mixed-phenotype acute leukemia (MPAL) is a rare disease. Treatment is often similar to that of acute lymphoblastic leukemia (ALL), but the outcome in adults and the role of allogeneic stem cell transplantation (AlloSCT) are not well defined. We report on 77 adult patients diagnosed with MPAL over the last 10 years and treated with a curative intent.

Comparison between azacitidine and decitabine as front-line therapy in elderly acute myeloid leukemia patients not eligible for intensive chemotherapy.

We compared the efficacy of azacitidine (AZA) and decitabine (DEC) in elderly patients with untreated AML, diagnosed according to WHO criteria. In the two groups, we evaluated complete remission (CR), overall survival (OS) and disease free survival (DFS). The AZA and DEC groups included 139 and 186 patients, respectively.

AVALON: The Italian cohort study on real-life efficacy of hypomethylating agents plus venetoclax in newly diagnosed or relapsed/refractory patients with acute myeloid leukemia.

Background: Venetoclax in combination with hypomethylating agents (HMA) is revolutionizing the therapy of acute myeloid leukemia (AML). However, evidence on large sets of patients is lacking, especially in relapsed or refractory leukemia.

Methods: AVALON is a multicentric cohort study that was conducted in Italy on patients with AML who received venetoclax-based therapies from 2015 to 2020.

Incidence, treatment and outcome of central nervous system relapse in adult acute lymphoblastic leukaemia patients treated front-line with paediatric-inspired regimens: A retrospective multicentre Campus ALL study.

Within the Campus ALL network we analyzed the incidence, characteristics, treatment and outcome of a central nervous system (CNS) relapse in 1035 consecutive adult acute lymphoblastic leukemia (ALL) patients treated frontline with pediatric-inspired protocols between 2009 and 2020. Seventy-one patients (6.8%) experienced a CNS recurrence, more frequently in T- (28/278; 10%) than in B-ALL (43/757; 5.

ATM/ATR kinases link the synaptonemal complex and DNA double-strand break repair pathway choice.

DNA double-strand breaks (DSBs) are deleterious lesions, which must be repaired precisely to maintain genomic stability. During meiosis, programmed DSBs are repaired via homologous recombination (HR) while repair using the nonhomologous end joining (NHEJ) pathway is inhibited, thereby ensuring crossover formation and accurate chromosome segregation. How DSB repair pathway choice is implemented during meiosis is unknown.

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).

Hematological disorders after salvage PARPi treatment for ovarian cancer: Cytogenetic and molecular defects and clinical outcomes.

Inhibitors of poly(ADP-ribose) polymerase (PARPi) are increasingly employed as salvage therapy in epithelial ovarian cancer (EOC), but cytotoxic drug exposure along with PARP inhibition may favor development of hematological disorders. In our study, of 182 women with EOC treated with PARPi, 16 (8.7%) developed therapy-related myeloid neoplasms (t-MNs), with 12 cases of myelodysplasia and 4 of acute myeloid leukemia.

HHV8-Negative Effusion-Based Large B Cell Lymphoma Arising in Chronic Myeloid Leukemia Patients under Dasatinib Treatment: A Report of Two Cases.

Tyrosine kinase inhibitors (TKIs) are the treatment of choice for BCR-ABL1-positive chronic myeloid leukemia (CML). Although TKIs have substantially improved prognosis of CML patients, their use is not free of adverse effects. Dasatinib is a second generation TKI frequently associated with pleural effusion in up to 33% of patients.

Validation of the "fitness criteria" for the treatment of older patients with acute myeloid leukemia: A multicenter study on a series of 699 patients by the Network Rete Ematologica Lombarda (REL).

Objectives: Treatment of older patients with acute myeloid leukemia (AML) is still controversial. To facilitate treatment decisions, the "fitness criteria" proposed by Ferrara et al. (Leukemia, 2013), including age > 75 years, performance status and comorbidities, were verified retrospectively in 699 patients with AML (419 de-novo, 280 secondary AML), diagnosed at 8 Hematological Centers (REL).

Clinical presentation, diagnosis and management of therapy-related hematological disorders in women with epithelial ovarian cancer treated with chemotherapy and poly-ADP-ribose polymerase inhibitors: A single-center experience.

We investigated the occurrence and management of therapy-related hematological disorders (tr-HDs) in women with epithelial ovarian cancer (EOC) exposed to poly-ADP-ribose polymerase inhibitors (PARPi), after previous chemotherapy. We analyzed 130 consecutive EOC patients treated with PARPi at the European Institute of Oncology, Milan. In line with the literature, overall survival of the entire population was 37% at 5.

Clinical significance of chromatin-spliceosome acute myeloid leukemia: a report from the Northern Italy Leukemia Group (NILG) randomized trial 02/06.

Secondary acute myeloid leukemia (sAML) after myelodysplastic or myeloproliferative disorders is a high-risk category currently identified by clinical history or specific morphological and cytogenetic abnormalities. However, in the absence of these features, uncertainties remain to identify the secondary nature of some cases otherwise defined as de novo AML. To test whether a chromatin-spliceosome (CS) mutational signature might better inform the definition of the de novo AML group, we analyzed a prospective cohort of 413 newly diagnosed AML patients enrolled into a randomized clinical trial (NILG AML 02/06) and provided with accurate cytogenetic and molecular characterization.