Chronic lymphocytic leukemia, in spite of recent advancements, is still an incurable disease; the majority of patients eventually acquire resistance to treatment through relapses. In all subtypes of chronic lymphocytic leukemia, the disruption of normal B-cell homeostasis is thought to be mostly caused by the absence of apoptosis. Consequently, apoptosis induction is crucial to the management of this illness. Damaged biological components can accumulate as a result of the oxidation of intracellular lipids, proteins, and DNA by reactive oxygen species. It is possible that cancer cells are more susceptible to apoptosis because of their increased production of reactive oxygen species. An excess of reactive oxygen species can lead to oxidative stress, which can harm biological elements like DNA and trigger apoptotic pathways that cause planned cell death. In order to upset the balance of oxidative stress in cells, recent therapeutic treatments in chronic lymphocytic leukemia have focused on either producing reactive oxygen species or inhibiting it. Examples include targets created in the field of nanomedicine, natural extracts and nutraceuticals, tailored therapy using biomarkers, and metabolic targets. Current developments in the complex connection between apoptosis, particularly ferroptosis and its involvement in epigenomics and alterations, have created a new paradigm.

Redox adaptation is essential for human health, as the physiological quantities of non-radical reactive oxygen species operate as the main second messengers to regulate normal redox reactions by controlling several sensors. An abnormal increase reactive oxygen species, called oxidative stress, induces biological injury. For this reason, variations in oxidative stress continue to receive consideration as a possible approach to treat leukemic diseases. However, the intricacy of redox reactions and their effects might be a relevant obstacle; consequently, and alongside approaches aimed at increasing oxidative stress in neoplastic cells, antioxidant strategies have also been suggested for the same purpose. The present review focuses on the molecular processes of anomalous oxidative stress in acute myeloid and acute lymphoblastic leukemias as well as on the oxidative stress-determined pathways implicated in leukemogenic development. Furthermore, we review the effect of chemotherapies on oxidative stress and the possibility that their pharmacological effects might be increased by modifying the intracellular redox equilibrium through a pro-oxidant approach or an antioxidant strategy. Finally, we evaluated the prospect of varying oxidative stress as an efficacious modality to destroy chemoresistant cells using new methodologies. Altering redox conditions may be advantageous for inhibiting genomic variability and the eradication of leukemic clones will promote the treatment of leukemic disease.

Multiple myeloma and monoclonal gammopathy of undetermined significance are plasma cell dyscrasias characterized by monoclonal proliferation of pathological plasma cells with uncontrolled production of immunoglobulins. Autoimmune pathologies are conditions in which T and B lymphocytes develop a tendency to activate towards self-antigens in the absence of exogenous triggers. The aim of our review is to show the possible correlations between the two pathological aspects. Molecular studies have shown how different cytokines that either cause inflammation or control the immune system play a part in the growth of immunotolerance conditions that make it easier for the development of neoplastic malignancies. Uncontrolled immune activation resulting in chronic inflammation is also known to be at the basis of the evolution toward neoplastic pathologies, as well as multiple myeloma. Another point is the impact that myeloma-specific therapies have on the course of concomitant autoimmune diseases. Indeed, cases have been observed of patients suffering from multiple myeloma treated with daratumumab and bortezomib who also benefited from their autoimmune condition or patients under treatment with immunomodulators in which there has been an arising or worsening of autoimmunity conditions. The role of bone marrow transplantation in the course of concomitant autoimmune diseases remains under analysis.

Menin inhibitors are the first targeted therapies for KMT2A-rearranged and NPM1-mutated acute leukemias, addressing a significant unmet need in these high-risk subtypes. Revumenib received approval in 2024–2025 for relapsed or refractory KMT2A-rearranged acute leukemia and NPM1-mutated AML. The AUG-MENT-101 trial reported a 23% composite complete remission rate in heavily pretreated patients, with 61% of responders achieving MRD negativity. Several menin inhibitors, including ziftomenib, bleximenib, and enzomenib, are in clinical development. They demonstrate similar efficacy, but their safety profiles differ, especially regarding QTc prolongation and coverage of resistance mutations. Combination therapies with azacitidine and venetoclax or intensive chemotherapy have achieved high response rates in newly diagnosed patients, supporting their potential use in frontline treatment. Acquired resistance, often due to MEN1 mutations at the drug-binding interface, occurs in about 40% of cases. Distinct resistance patterns among menin inhibitors suggest the possibility of sequential therapy. Approximately 30–40% of responders in relapsed or refractory trials proceeded to allogeneic transplantation, which remains a key pathway to potential cure. This review examines the molecular mechanisms of the menin-KMT2A interaction, and summarizes clinical trial data on the efficacy and safety of menin inhibitors as monotherapy and in combination.

Hemophilia, an X-linked bleeding disorder, is characterized by a deficiency in coagulation factors. It manifests as spontaneous bleeding, leading to severe complications if not properly managed. In contrast, acquired hemophilia is an autoimmune condition marked by the development of inhibitory antibodies against coagulation factors. Both forms present significant diagnostic and therapeutic challenges, highlighting the need for advanced genetic, molecular, laboratory, and clinical assessments. Recent advances in artificial intelligence have opened new avenues for the management of hemophilia. Machine learning and deep learning technologies enhance the ability to predict bleeding risks, optimize treatment regimens, and monitor disease progression with greater precision. Artificial intelligence-driven applications in medical imaging have also improved the detection of joint damage and hemarthrosis, ensuring timely interventions and better clinical outcomes. Moreover, the integration of artificial intelligence into clinical practice holds the potential to transform hemophilia care through predictive analytics and personalized medicine, promising not only faster and more accurate diagnoses but also a reduction in long-term complications. However, ethical considerations and the need for data standardization remain critical for its widespread adoption. The application of artificial intelligence in hemophilia represents a paradigm shift towards precision medicine, with the promise of significantly improving patient outcomes and quality of life.

Background/Objectives: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm driven by dysregulated JAK-STAT signaling, characterized by progressive marrow fibrosis, splenomegaly, constitutional symptoms, and increased risk of leukemic transformation. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative intervention. In Italy, allo-HCTs for myeloproliferative neoplasms (MPN, i.e., myelofibrosis, polycythaemia vera, and essential thrombocythaemia combined) increased by 163% from 2015 to 2025; MF-specific procedure counts were not separately available in this registry export, so this figure should not be read as MF-specific, with MPN accounting for 8% of all allogeneic procedures (n = 171) in 2025, showing a 29.5% year-on-year increase from 2024. Concurrently, the demographic profile shifted, with individuals aged 60 and over representing 38% of all recipients, surpassing other age groups for the first time in 2025. Results: This review synthesizes current evidence on transplant indications and timing, pre-transplant management, donor selection, and conditioning regimen optimization, emphasizing the emerging role of treosulfan-based and dual-alkylator platforms, including the thiotepa–treosulfan–fludarabine (TTF) regimen. Post-transplant molecular MRD monitoring and relapse management are also discussed. Three-year overall survival in myelofibrosis ranges from about 59% to 67%, depending on donor type, with outcomes improving due to better patient selection, optimized conditioning, and supportive care. Conclusions: Prospective randomized trials are urgently needed to validate optimal conditioning intensity, the role of novel JAK inhibitors in the peri-transplant period, and MRD-guided pre-emptive strategies.