Clinical and molecular characterization of TP53-mutant acute lymphoblastic leukemia in adults.

TP53-mutant acute lymphoblastic leukemia (ALL) in adults is a high-risk subtype with poor outcomes, yet its molecular landscape and clinical implications remain incompletely defined. In this multi-institutional study of 830 adult ALL patients treated at eight academic centers between 2010 and 2024, we demonstrated that TP53 mutations are independent predictors of inferior overall survival in both B-ALL (median, 1.9 vs 5 years) and T-ALL (1.

Longer time from diagnosis to initiation of hypomethylating agents plus venetoclax for acute myeloid leukemia does not worsen survival: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases (COMMAND).

A diagnosis of acute myeloid leukemia (AML) has been considered an oncologic emergency. However, the prevailing wisdom to quickly administer AML-directed therapy is often in conflict with the time needed to complete the evaluation of actionable AML disease biology. Previous studies in intensively treated patients reported that time from date of diagnosis to treatment start date (TDT) did not impact survival outcomes.

Outcomes for Patients With Myeloid Neoplasms Treated With Chemotherapy Plus Venetoclax After Prior Venetoclax Therapy.

Background: Outcomes for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) that have progression after treatment with hypomethylating agent (HMA) and venetoclax (VEN) are poor. However, data for chemotherapy and VEN (C+VEN) therapy after prior treatment with HMA+VEN are limited.

Methods: We identified 18 patients with AML or MDS/AML who received C+VEN after prior HMA+VEN.

SOHO State of the Art Updates and Next Questions | Challenging Scenarios in the Management of Myeloproliferative Neoplasms.

Philadelphia-chromosome negative (Ph-neg) myeloproliferative neoplasms (MPNs) carry a variable rate of progression to the fibrotic stage of disease and/or the accelerated/blast-phase (AP/BP) of disease. Many of the challenging management scenarios that arise in the treatment of MPNs occur in those with higher-risk myelofibrosis (MF) or MPN-AP/BP. In this review we will focus upon 3 challenging clinical scenarios pertinent to the management of high-risk MPNs.

CD58 expression does not impact response to inotuzumab ozogamicin in patients with B-cell acute lymphoblastic leukemia.

Background: CD58 loss has been described as a mechanism of resistance to blinatumomab and chimeric antigen receptor T-cell therapy, functioning as a modulator of response to T-cell activation.

Methods: Using flow cytometry, we evaluated the impact of CD58 mean fluorescence intensity (MFI) on the probability of achieving measurable residual disease (MRD) negativity in patients with B-cell acute lymphoblastic leukemia treated with inotuzumab ozogamicin (InO).

Results: The odds ratio of achieving MRD negativity was 1.

Mayo Genetic Risk Models for Newly Diagnosed Acute Myeloid Leukemia Treated With Venetoclax + Hypomethylating Agent.

Patients with newly diagnosed acute myeloid leukemia (ND-AML) derive variable survival benefit from venetoclax + hypomethylating agent (Ven-HMA) therapy. The primary objective in the current study was to develop genetic risk models that are predictive of survival and are applicable at the time of diagnosis and after establishing treatment response. Among 400 ND-AML patients treated with Ven-HMA at the Mayo Clinic, 247 (62%) achieved complete remission with (CR) or without (CRi) count recovery.

Somatic co-alteration signatures are prognostic in high-grade TP53-mutated myeloid neoplasms.

To assess the relevance of co-occurring somatic mutations in TP53-mutated myeloid neoplasms with ≥10% blasts, we pooled 325 individuals from 10 centres. We focused on comparing three published somatic co-alteration signatures comprising (1) nine MDS-related genes ('ICC-MDSR'), (2) ICC-MDSR + additional secondary mutations-related genes ('Tazi signature') and (3) EPI6 (comprising six genes). Outcomes examined were 24-month overall survival (OS24) and front-line complete response (CR1).

Prevention and treatment of transformation of myeloproliferative neoplasms to acute myeloid leukemia.

Philadelphia-chromosome negative myeloproliferative neoplasms (MPN) are hematopoietic stem disorders with a risk of progression to an accelerated phase (AP) or blast phase (BP) that is influenced by clinical, pathological, cytogenetic, and molecular variables. Overall survival of patients with MPN-AP/BP is limited with current treatment approaches, particularly in those patients who cannot receive an allogeneic hematopoietic stem cell transplant (allo-HCT). In addition, long-term survival with allo-HCT is predominantly seen in chronic-phase MPN, which suggests that the ideal time for intervention may be before the MPN evolves to AP/BP.

A multicenter phase 2 clinical trial of low-dose subcutaneous decitabine in myelofibrosis.

Myelofibrosis (MF) in the chronic phase is a challenging disease to treat, and conventional treatment options are geared toward symptom palliation. In this prospective, multicenter, phase 2 trial, 21 patients with MF (18 chronic phase, 2 accelerated phase, and 1 blast phase) were treated with a 10-day schedule of subcutaneous decitabine at 0.3 mg/kg per day.

Real world predictors of response and 24-month survival in high-grade TP53-mutated myeloid neoplasms.

Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24).

NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended.

Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era.

Progression of myeloproliferative neoplasms (MPNs) to accelerated or blast phase is associated with poor survival outcomes. Since 2017 there have been several therapies approved for use in acute myeloid leukemia (AML); these therapies have been incorporated into the management of accelerated/blast-phase MPNs (MPN-AP/BP). We performed a multicenter analysis to investigate outcomes of patients diagnosed with MPN-AP/BP in 2017 or later.

Transfusion management and hemoglobin-based oxygen carrier treatment in a patient with anti-Rh17 antibody.

Background: A 54-year-old Hispanic OPos female with known history of anti-Rh17 antibodies was diagnosed with Philadelphia-Chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). Rh17, also known as Hr, is a high-frequency antigen composed of several epitopes on the RhCE protein. Anti-Rh17 antibodies can be made by individuals with missing or varied C/c, E/e antigens.

Durable responses in acute lymphoblastic leukaemia with the use of FLT3 and IDH inhibitors.

Data regarding the use of FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase 1/2 (IDH1/2) inhibitors in acute lymphoblastic leukaemia (ALL) are lacking. We identified 14 patients with FLT3- or IDH1/2-mutated ALL. Three early T-cell precursor-ALL patients received FLT3 or IDH2 inhibitors.