Old Therapy, New Questions: Rethinking Phlebotomy in a Pharmacologic Landscape.

Therapeutic phlebotomy remains a key intervention in the management of erythrocytosis and iron overload disorders, particularly polycythemia vera (PV) and hereditary hemochromatosis. Despite its historical origins as an ancient practice, venesection continues to be recommended in international guidelines for the reduction of hematocrit and iron burden, thereby mitigating thrombotic and organ-related complications. However, the evolving landscape of targeted pharmacologic therapies is reshaping the therapeutic paradigm.

Does the Timing of Response Impact the Outcome of Relapsed/Refractory Acute Myeloid Leukemia Treated with Venetoclax in Combination with Hypomethylating Agents? A Proof of Concept from a Monocentric Observational Study.

: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders.

Correction: Mancuso et al. Forcing Ahead: Second-Line Treatment Options for Lenalidomide-Refractory Multiple Myeloma. 2025, , 1168.

The authors have separated the affiliations originally listed in affiliation 4-this is so both affiliations can be organized from subordinate to superior [...

Real-World Outcomes in -ITD Mutated Acute Myeloid Leukemia: Impact of NPM1 Mutations and Allogeneic Transplantation in a Retrospective Unicentric Cohort.

: Acute myeloid leukemia (AML) with internal tandem duplication (-ITD) mutations carries a poor prognosis. While inhibitors like midostaurin show benefits in combination with chemotherapy, the role of allelic ratio (AR), mutation status, and hematopoietic stem cell transplantation (HSCT) remains uncertain. Real-world data can help refine prognostic classification and treatment strategies.

Length of Washout Period After Remission Does Not Influence Relapse Risk in Patients with Acute Myeloid Leukemia Treated with Hypomethylating Agents Combined with Venetoclax.

The combination of venetoclax (VEN) and hypomethylating agents (HMA), such as azacitidine (AZA) or decitabine (DEC), has transformed the treatment landscape for acute myeloid leukemia (AML) in patients unfit for intensive chemotherapy. However, optimal management of neutropenia and the impact of post-remission treatment interruptions (washouts) remain unclear. This study aimed to evaluate the safety and efficacy of post-remission washouts and their effect on clinical outcomes.

The Coiled Coil and C2 Domains Modulate BCR Localization and BCR-ABL1 Compartmentalization, Transforming Activity and TKI Responsiveness.

The BCR-ABL1 chimeric oncoprotein plays a pivotal role in the pathogenesis of Chronic Myeloid Leukemia (CML) as its constitutive kinase activity transforms the hematopoietic stem cell, promoting pro-survival signaling. We and others have previously shown that the manipulation of BCR-ABL1 catalytic activity modulates its intracellular localization, thereby transforming the culprit of CML into a pro-apoptotic protein that selectively kills leukemic cells. Here, we investigated the role of the BCR coiled-coil and C2 domains on BCR-ABL1 intracellular localization and leukemogenic potential.

COVID-19 Vaccine Experience: Loss of Humoral Response Following Autologous Stem Cell Transplantation in Multiple Myeloma Patients and Positive Effect of Booster Dose.

: This prospective study investigated the impact of high-dose chemotherapy and autologous stem cell transplantation (ASCT) on anti-COVID-19 antibody levels in previously vaccinated multiple myeloma (MM) patients with confirmed antibody response (AR). : All patients underwent at least a two-dose regimen mRNA vaccination and later received a high-dose melphalan conditioning regimen and ASCT. : Fourteen MM patients with confirmed AR underwent a total of nineteen ASCT reinfusions; their median age was 55 (34-67).

In vivo Effects of Disease-modifying Therapies on Immunological Subsets in Patients with Relapsing-Remitting Multiple Sclerosis.

Background: Disease-modifying therapies (DMTs) are aimed at controlling Multiple Sclerosis disease by modulating or suppressing the immune system. However, there is limited data on changes in immune cell subsets induced by these treatments.

Objective: To assess differences in myeloid, T-, and B-cell subsets in the peripheral blood of relapsing- remitting MS (RR-MS) patients treated with different DMTs.

Correction: Sgherza et al. Efficacy and Safety of Isatuximab, Carfilzomib, and Dexamethasone (IsaKd) in Multiple Myeloma Patients at the First Relapse After Autologous Stem Cell Transplantation and Lenalidomide Maintenance: Results from the Multicenter, Real-Life AENEID Study. 2025, , 595.

In the original publication [...

Measurement of Immunoglobulin Intraclonal diversification refines the clinical impact of IGHV mutational status in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) cells may bear mutations in IGHV genes, the 2%-cutoff allowing to discriminate two subsets, unmutated (U)- or mutated (M)-CLL, with different clinical course. IGHV genes may also incorporate additional ongoing mutations, a phenomenon known as intraclonal diversification (ID). Here, through an original bioinformatic workflow for NGS data, we used the inverse Simpson Index (iSI) as diversity measure among IGHV sequences to dichotomize cases with different ID levels into ID (iSI ≥ 1.

Outcomes of Patients With Extramedullary Disease in Triple-Class Exposed Relapsed/Refractory Multiple Myeloma From the Pooled LocoMMotion and MoMMent Studies.

Background: Patients with relapsed/refractory multiple myeloma (RRMM) who develop extramedullary disease (EMD) generally have a poor prognosis, highlighting the urgent need for new therapies. We report effectiveness outcomes and safety in patients with and without EMD from the pooled analysis of LocoMMotion and MoMMent.

Methods: LocoMMotion and MoMMent-1 are prospective, noninterventional, consecutive studies assessing the evolving standard of care from 20192022 in patients with triple-class exposed RRMM.

Lenalidomide maintenance after bortezomib, thalidomide and dexamethasone (VTD) induction and autologous stem cell transplantation: an Italian real-life study of 602 patients.

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Efficacy and Safety of Isatuximab, Carfilzomib, and Dexamethasone (IsaKd) in Multiple Myeloma Patients at the First Relapse After Autologous Stem Cell Transplantation and Lenalidomide Maintenance: Results from the Multicenter, Real-Life AENEID Study.

: In the randomized, phase-3 IKEMA trial, the triplet isatuximab, carfilzomib, and dexamethasone (IsaKd) demonstrated superior clinical benefit compared to those of carfilzomib and dexamethasone alone in patients with relapsed/refractory multiple myeloma after 1-3 prior treatments. : Our real-world, AENEID study aimed to evaluate the efficacy and safety of IsaKd in patients who relapsed after frontline lenalidomide treatment, poorly represented in the IKEMA trial. Specifically, in the present multicenter analysis, we enrolled eighty-two patients who received, between April 2022 and September 2024 and outside of clinical trials, at least one cycle of IsaKd as a second-line treatment at the first relapse after induction therapy, autologous stem cell transplantation (ASCT), and lenalidomide maintenance.

Forcing Ahead: Second-Line Treatment Options for Lenalidomide-Refractory Multiple Myeloma.

The therapeutic landscape for multiple myeloma has gradually expanded in recent decades, leading to unprecedented deep and sustained responses as well as remarkable improvements in patient survival. Nonetheless, changes in treatment algorithms have raised new demands for patients with relapsed/refractory disease, as prior exposure and refractoriness to prior therapies impact the choice of subsequent treatments. In particular, refractoriness to lenalidomide-an established backbone of treatment in both front-line and maintenance settings and a key component of many approved regimens used in relapsed disease-is associated with suboptimal clinical outcomes.

Navigating acute myeloid leukemia towards better outcomes: Treatment pathways and challenges for patients ineligible for intensive chemotherapy.

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that affects primarily older individuals. Patients ineligible to receive intensive standard chemotherapy followed by consolidation with/without hematopoietic stem cell transplant have a suboptimal prognosis. In recent years, significant advances have been made in the AML field leading to the development of new anti-leukemic approaches, including lower-intensity therapies specifically developed for patients who are ineligible for intensive chemotherapy.

Chemotherapy extravasation: diagnosis, prevention and management.

Chemotherapy extravasation, the unintended leakage of cytotoxic drugs into surrounding tissues, is a significant complication in oncological treatments, potentially leading to severe tissue damage and long-term consequences. This review explores the factors influencing extravasation risk, including infusion site, patient comorbidities and the physicochemical properties of drugs. Early detection is crucial to prevent irreversible damage.

INO-CD22: A multicenter, real-world study of inotuzumab ozogamicin safety and effectiveness in adult patients with relapsed/refractory acute lymphoblastic leukemia.

Background: Inotuzumab ozogamicin (IO) has helped to change the treatment paradigm in B-cell acute lymphoblastic leukemia (B-ALL) but real-world data are limited.

Methods: The INO-CD22 study is a multicenter retrospective cohort study of adult patients with relapsed/refractory B-ALL treated with IO in 24 Italian centers from 2014 to 2019, with the aim of assessing the response, survival, and toxicity of IO.

Results: Data for 73 eligible patients were obtained: the median age at the start of IO treatment was 52.

Prognostic Significance of +1q Alterations in Relapsed/Refractory Multiple Myeloma Treated With Daratumumab-, Elotuzumab-, and Carfilzomib-Based Triplet Regimens: A Multicenter Real-World Analysis of 635 Patients.

Relapsed/refractory multiple myeloma (RRMM) research on the impact of +1q abnormalities in real-world settings is limited. This study evaluated the prognostic and predictive significance of 1q gain [gain(1q)] and amplification [ampl(1q)] in 635 RRMM patients treated with daratumumab-, elotuzumab-, and carfilzomib-based triplet regimens. Patients with +1q abnormalities had lower deep response rates [≥ CR: 9.

No Benefit from Hydroxyurea Pre-Treatment in Frontline Chronic Myeloid Leukemia Therapy and Evidence of Quantitative Changes in the Transcript Level.

Hydroxyurea (HU) cytoreduction is usually administered to patients with chronic myeloid leukemia before starting any tyrosine kinase inhibitors (TKIs) therapy. However, up to date, there is no evidence of any benefit of hydroxyurea pre-treatment. Conversely, evidence has been provided on both the prognostic significance of the quantitative assessment of expression at diagnosis and the individual decline of the slope.

Inhibitor Eradication in Postpartum Acquired Haemophilia A: Real-Life Case Series and Literature Review.

Background: Acquired haemophilia A (AHA) is a rare and severe bleeding disorder generally associated with pregnancy or aging. Spontaneous remission and prompt inhibitor eradication are described more frequently in postpartum cases. We evaluated retrospectively 15 postpartum AHA cases between 2007 and 2023 in order to evaluate response in terms of inhibitor eradication.

Up-front blinatumomab improves MRD clearance and outcome in adult Ph- B-lineage ALL: the GIMEMA LAL2317 phase 2 study.

The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Leucemia Acuta Linfoblastica (LAL) 2317 protocol investigated the frontline chemotherapy-blinatumomab combination in adult Philadelphia chromosome/BCR::ABL1 rearrangement-negative (Ph-) CD19+ B-lineage acute lymphoblastic leukemia (B-ALL) to improve minimal residual disease (MRD) response and clinical outcome. Two cycles of IV blinatumomab were administered after chemotherapy cycles 3 and 6. The primary end point was the rate of molecular MRD negativity after blinatumomab 1.

Immune Response and Breakthrough Infection Risk After SARS-CoV-2 Vaccines in Patients with Hemoglobinopathy: A Single Center Experience.

Background: Immune system impairment is frequently reported in patients affected by hemoglobinopathies due to various mechanisms, including iron accumulation, antigenic stimulation due to numerous transfusions, chronic hemolysis, and a general hyperinflammatory state. For these reasons, the antigenic immune response after a vaccine risks being ineffective.

Methods: We evaluated the anti-spike IgG production after two doses of vaccine for SARS-CoV-2 in patients affected by hemoglobinopathies.

BNT162b2 mRNA vaccination affects the gut microbiome composition of patients with follicular lymphoma and chronic lymphocytic leukemia.

Background: In both chronic lymphatic leukemia (CLL) and follicular lymphoma (FL) immunotherapy determines B-depletion that leads to temporary suppression of humoral immunity, which is clinically relevant especially during the COVID-19 pandemic, when most patients in the first wave received the BNT162b2 vaccine during anti-neoplastic treatment.

Methods: To capture changes in the immunome and microbiome composition in CLL and FL patients upon mRNA-based vaccination, we designed a prospective, longitudinal study to profile both the humoral and the cellular response after exposure to the BNT162b2 COVID-19 vaccine.

Results: In both CLL patients and FL patients, the second and third administrations of the BNT162b2 vaccine increased the titer of specific antibodies against SARS-CoV-2.