Clinical and biological advances of critical complications in acute myeloid leukemia.

Managing acute myeloid leukemia (AML) and its critical complications requires understanding the complex interplay between disease biology, treatment strategies, and patient characteristics. Complications like sepsis, acute respiratory failure (ARF), hyperleukocytosis, coagulopathy, tumor lysis syndrome (TLS) and central nervous system (CNS) involvement present unique challenges needing precise evaluation and tailored interventions. Venetoclax-induced TLS and differentiation syndrome (DS) from IDH1/IDH2 or menin inhibitors highlight the need for ongoing research and innovative approaches.

Different prognosis according to treatment in patients with acute promyelocytic leukemia: How the outcome changed over time.

A comprehensive analysis of 220 patients diagnosed with APL between 1993 and 2022 is here reported. Overall, 214 patients (97.2%) received induction therapy.

Safety and Efficacy of TKIs in very Elderly Patients (≥75 Years) with Chronic Myeloid Leukemia.

Background: While the outcomes of chronic phase chronic myeloid leukemia (CP-CML) patients aged over 65 years have been extensively evaluated in real-life experiences, limited data exist for the very elderly population (i.e., aged ≥ 75 years), especially for next-generation tyrosine kinase inhibitors (TKIs).

How to improve treatment-free remission eligibility in chronic myeloid leukaemia?

The achievement of treatment-free remission (TFR) has become a significant clinical end-point in the management of patients with chronic myeloid leukaemia (CML), providing an opportunity to discontinue therapy with tyrosine kinase inhibitors (TKIs) while maintaining deep molecular response (DMR). Early studies, such as the French STIM trial, have demonstrated that a portion of patients can maintain DMR after treatment cessation, with rates ranging from 40% to 50%, and most relapses occurring within the first 6 months. Key prognostic factors for successful TFR, including treatment duration, duration of DMR, risk scores, and transcript type, have been identified.

Validation of imatinib therapy failure score (IMTF) in chronic phase chronic myeloid leukemia in real life practice.

The outcome of chronic myeloid leukemia (CML) patients improved in the last decade. Clinical prognostic scoring systems aim to provide information about survival in the long-term, without determining from baseline the subset of patients who require a strictly monitoring because at increased risk of failure. Imatinib, the first-generation tyrosine kinase inhibitor (TKI), is still widely used as frontline treatment: recently, the imatinib therapy failure (IMTF) score was proposed to identify the failure free survival.

mutations in atypical chronic myeloid leukemia: a report of two cases.

Atypical chronic myeloid leukemia (aCML) is a rare MDS/MPN disease characterized by the absence of BCR::ABL1 rearrangement and well known typical mutations associated with myeloproliferative disorders. Mutational landscape associated with this disease was recently described with frequent involvement of SETBP1 and ETNK1 mutations. CCND2 mutations have not been frequently detected in MPN or MDS/MPN patients.

Systemic mastocytosis: 2023 update on diagnosis and management in adults.

Introduction: Systemic mastocytosis (SM) is a complex and heterogeneous disease, characterized by the clonal accumulation of mast cells in one or more organs. In 2022 both the World Health Organization (WHO) and the International Consensus Classification (ICC) modified the diagnostic and classification criteria of SM. Moreover, the identification of new clinical and molecular variables has improved prognostic tools and led to increasingly individualized therapeutic strategies.

Management of Chronic Myeloid Leukemia Patients in Later Lines: The Role of Ponatinib and New Compounds.

Limited therapeutic options and poor response probability still represent some unresolved issue in later lines chronic myeloid leukemia (CML) patients. In addition, sequential treatment is associated with reduced overall survival and may select new mutation, including the T315I, further reducing the therapeutic chances: outside the United States, ponatinib and allogenic stem cell transplant are the only available options. In the last decade, ponatinib improved outcomes in third-line patients, although limited by the risk of severe adverse occlusive events.

From bench to bedside: bridging the gaps in best practices for real-world chronic myeloid leukemia care.

Introduction: Although tyrosine kinase inhibitors (TKIs) determined an improvement of responses and overall survival (OS) in chronic phase chronic myeloid leukemia (CP-CML) patients, some patients still fail the achievement of important milestones.

Areas Covered: In this review, we focus on the need of appropriate molecular and mutational monitoring during TKI treatment with new laboratory tools and on new compounds developed to counteract the unmet clinical need in CP-CML.

Expert Opinion: The appropriate identification of BCR::ABL1 dependent and independent mechanisms of resistance with Next Generation Sequencing (NGS) and digital droplet PCR (ddPCR) can allow to improve the therapeutic strategies and prevent the onset of a failure to treatment.

Asciminib in chronic myeloid leukemia.

Despite the fact that, in the last years, life expectancy of chronic myeloid leukemia (CML) patients has reached that of the normal population, a significant proportion of CML patients is likely to fail treatment with first- or second-generation tyrosine kinase inhibitors (TKIs). Failure to first-line treatment is commonly due to molecular resistance or unbearable toxicity. New specific compounds are tested in this setting to fulfill this unmet clinical need in CML; of these, asciminib has shown efficacy based on allosteric inhibition which allows to overcome resistance and off-target toxicity.

CML Resistant to 2nd-Generation TKIs: Mechanisms, Next Steps, and New Directions.

Purpose Of Review: The clinical scenario for chronic myeloid leukemia patients rapidly changed after the introduction of tyrosine kinase inhibitors (TKIs). Second-generation TKIs as frontline treatment increased the rate of deep molecular responses without increasing the rate of overall survival. About 20% of patients experience resistance to these agents, needing alternative treatments.

Asciminib as a third line option in chronic myeloid leukemia.

Unmet needs remain in the treatment of chronic phase chronic myeloid leukemia (CML) in later lines. Sequential use of tyrosine kinase inhibitors (TKIs) is associated with decreased overall survival and emergence of new mutations, particularly the T315I mutation. Among the new drugs developed to overcome resistance and intolerance, the STAMP inhibitor asciminib (which specifically targets the ABL myristoyl pocket) is the first example of a drug that works by allosteric inhibition.

Management of chronic myeloid leukaemia patients treated with ponatinib in a real-life setting: A retrospective analysis from the monitoring registries of the Italian Medicines Agency (AIFA).

Real-world data on daily practice management, treatment modifications and outcome of a large cohort of chronic myeloid leukaemia (CML) patients treated with ponatinib was performed through monitoring Registries of the Italian Medicines Agency (AIFA). Overall, 666 CML subjects were included in the ponatinib registry from February 2015 to December 2020 and were eligible for analysis: 515 in chronic phase (CP), 50 in accelerated phase (AP) and 101 in blast crisis (BC). Median age at baseline was 58.