Mutational Landscape of Bone Marrow CD19 and CD138 Cells in Waldenström Macroglobulinemia (WM) and IgM Monoclonal Gammopathy of Undetermined Significance (IgM MGUS).

Background: Despite recurrent and activating mutations, including MYD88, CXCR4, ARID1A, KMT2D, and CD79B were identified, the genetic basis for Waldenström's Macroglobulinemia (WM) and the risk of progression of IgM MGUS to WM remain to be fully elucidated.

Methods: We investigated the mutation status of WM (n = 8), sWM (n = 7), and IgM MGUS (n = 5) patients, by performing high-throughput targeted AmpliSeq NGS on 117 target genes. Specifically, we analyzed the CD19+ cells from 15 WM/sWM patients and five IgM MGUS patients.

A GIMEMA survey on therapeutic use and response rates of FLT3 inhibitors in acute myeloid leukemia: Insights from Italian real-world practice.

Given the limited data on the real-life therapeutic use of feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) inhibitors in Italy, we surveyed investigators at 59 Italian hematology centers to gain insight into the proportion of acute myeloid leukemia (AML) patients receiving FLT3 inhibitors and we collected data on the efficacy and safety of these agents. The survey results showed that in the real-life setting the response rate of the 3/7 + midostaurin regimen in newly diagnosed FLT3-mutated AML and of gilteritinib in the relapsed/refractory AML were comparable to that reported in the registrative clinical trials. The 3/7 + midostaurin treatment resulted in a 63% of complete remission (CR) rates and gilteritinib in a 44% of CR rates.

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.

Impaired survival of patients with non donor-specific anti-HLA antibodies before HLA-mismatched allogeneic stem cell transplantation.

Background: While the detrimental role of donor-specific anti-HLA antibodies (DSAs) is well-described in the setting of hematopoietic stem cell transplantation (HSCT), few studies focus on non donor-specific ones and with controversial results.

Methods: We here report our monocenter experience on 64 adult patients receiving allogeneic HSCT from a HLA-mismatched donor between 2014 and 2022 who were tested for the presence of anti-HLA antibodies before transplant, focusing on fifteen patients with non donor-specific anti-HLA antibodies.

Results: The survival of patients with non donor-specific anti-HLA antibodies was inferior with respect to patients without anti-HLA antibodies and similar to patients with DSAs.

Exploring the administrative burden faced by hematologists: a comprehensive study in Italy.

Background: Administrative burdens have been identified as a major issue impacting patient care, professional practice, and the overall efficiency of healthcare systems. The aim of this study is to assess the administrative burden faced by Italian hematologists.

Methods: A cross-sectional survey that included both closed-ended quantitative questions and open-ended free text answer options was administered to 1,570 hematologists working with malignancies and members of Italian GIMEMA Foundation - Franco Mandelli ONLUS and the Italian Linfomi Foundation (FIL).

Cerebral Infectious Opportunistic Lesions in a Patient with Acute Myeloid Leukaemia: The Challenge of Diagnosis and Clinical Management.

Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis.

Communicating the diagnosis of a hematological neoplastic disease to patients' minor children: a multicenter prospective study.

Background: When a hematological malignancy is diagnosed, the whole family carries the burden of the disease; parents often try to protect minor children from suffering by avoiding communication about their disease. Since 2009, patients with minors at the Adult Hematology Division at San Gerardo Hospital (Monza) can take part in the "Emanuela Project": children can visit parents and talk with psychologists and hematologists, who explain the disease through simple metaphors.

Materials And Methods: The EMY STUDY aimed to evaluate the impact of illness-related communication on children's behavior, comparing Monza's experience with other Hematology Units, where the communication is delegated to parents or psychological support.

Anti-CD38 monoclonal antibody impairs CD34+ mobilization and affects clonogenic potential in multiple myeloma patients.

Background: Induction with daratumumab-based regimens followed by autologous stem cell transplantation is the current standard for newly diagnosed multiple myeloma (NDMM) patients eligible for intensive chemotherapy. However, concerns emerged regarding potential negative effects following daratumumab-based treatment on CD34+ mobilization. We here compared CD34+ mobilization and clonogenic potential between daratumumab and non-daratumumab based therapy without upfront plerixafor administration among patients affected by NDMM.

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.

Sabatolimab plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes (STIMULUS-MDS1): a randomised, double-blind, placebo-controlled, phase 2 trial.

Background: Sabatolimab is an immunotherapy targeting T-cell immunoglobulin domain and mucin domain-3 (TIM-3), an immuno-myeloid regulator expressed on immune cells and leukaemic stem cells. In this trial, we compared the efficacy and safety of sabatolimab plus hypomethylating agent with placebo plus hypomethylating agents in previously untreated patients with higher-risk myelodysplastic syndromes.

Methods: STIMULUS-MDS1 was a multicentre, randomised, double-blind, placebo-controlled, phase 2 study done at 54 investigational sites in 17 countries.

A Nine-Gene Expression Signature Distinguished a Patient with Chronic Lymphocytic Leukemia Who Underwent Prolonged Periodic Fasting.

: This study aimed to investigate the causes of continuous deep fluctuations in the absolute lymphocyte count (ALC) in an untreated patient with Chronic Lymphocytic Leukemia (CLL), who has had a favorable prognosis since the time of diagnosis. Up until now, the patient has voluntarily chosen to adopt a predominantly vegetarian and fruitarian diet, along with prolonged periods of total fasting (ranging from 4 to 39 days) each year. : For this purpose, we decided to analyze the whole transcriptome profiling of peripheral blood (PB) CD19+ cells from the patient (#1) at different time-points vs.

Cordycepin (3'dA) Induces Cell Death of AC133 Leukemia Cells via Re-Expression of and Down-Modulation of .

Wnt/β-catenin signaling is critically required for the development and maintenance of leukemia stem cells (LSCs) in acute myeloid leukemia (AML) by constitutive activation of myeloid regeneration-related pathways. Cell-intrinsic activation of canonical Wnt signaling propagates in the nucleus by β-catenin translocation, where it induces expression of target oncogenes such as , and . As the Wnt/β-catenin pathway is now well established to be a key oncogenic signaling pathway promoting leukemic myelopoiesis, targeting it would be an effective strategy to impair LSC functionality.

Multidimensional Results and Reflections on CAR-T: The Italian Evidence.

The present study aims at defining the economic and organizational impacts of the introduction of chimeric antigen receptor T-cell therapy (CAR-T) in Italy, for the management of diffuse large B-cell lymphoma (DLBCL) patients in third-line therapy, defining the overall level of sustainability for both hospitals and the National Healthcare System (NHS). The analysis focused on CAR-T and Best Salvage Care (in the following BSC), assuming the Italian hospital and NHS perspectives, over a 36-month time horizon. Process mapping and activity-based costing methodologies were applied to collect the hospital costs related to the BSC and CAR-T pathways, including adverse event management.

Current Treatment Options and the Role of Functional Status Assessment in Classical Hodgkin Lymphoma in Older Adults: A Review.

Along with the fact that classical Hodgkin lymphoma (cHL) in older adults is frequently considered biologically different from cHL in younger patients, its most distinctive feature is its dismal clinical outcome due to the decreased effectiveness and greater toxicity of therapies. Although strategies to mitigate specific toxicities (e.g.