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.

Characteristics of patients with newly diagnosed acute myeloid leukemia not receiving treatment.

Not available.

Impact of transplant conditioning, NPM1 mutations, and measurable residual disease in FLT3-ITD acute myeloid leukemia.

We conducted a post-hoc analysis of data from BMT CTN 1506 (MORPHO), a randomized trial of gilteritinib versus placebo as post-transplantation maintenance for patients with FLT3-ITD-mutated acute myeloid leukemia (AML) undergoing allogeneic hematopoietic cell transplantation (HCT), focusing the interactions between conditioning regimen intensity, measurable residual disease (MRD), and NPM1 co-mutation status reported from diagnosis. Comparing FLT3-ITD MRD before and after conditioning, there was no difference between myeloablative conditioning (MAC) and reduced intensity conditioning (RIC) in eradication or reduction of FLT3-ITD MRD. For participants who were FLT3-ITD MRD-negative pre-HCT, there was no difference in the cumulative incidence of relapse during follow-up between those receiving MAC versus RIC.

Multipotent lineage potential in B cell acute lymphoblastic leukemia is associated with distinct cellular origins and clinical features.

Developmental origins and their associations with lineage plasticity and treatment response in B-cell progenitor acute lymphoblastic leukemia (B-ALL) are mostly unexplored. Here, we integrated single-cell transcriptome sequencing (scRNA-seq) of 89 B-ALL samples with a single-cell atlas of normal human B cell development incorporating functional and molecular assays. We observed subtype- and sample-dependent correlation with normal developmental stage, with intra-subtype and intra-patient heterogeneity.

Differentiation-dependent EBF1 activity determines CD22 transcription and leukemia sensitivity to inotuzumab ozogamicin.

Inotuzumab ozogamicin (InO) is an antibody-calicheamicin conjugate with high efficacy in lymphoid malignancies. It targets the B-cell surface protein CD22, which is expressed in most B-cell acute lymphoblastic leukemia (B-ALL) cases, albeit with variable intensity. However, factors governing CD22 expression and thus leukemia sensitivity to InO remain incompletely understood.

Comparison of Chimerism Kinetics and Associated Outcomes in Patients Receiving Post-Transplant Cyclophosphamide Versus Methotrexate based GVHD Prophylaxis Following Allogeneic Hematopoietic Cell Transplant.

Post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is now being used beyond haploidentical (HID) allogeneic hematopoietic cell transplant (alloHCT). However, the kinetics of chimerism in patients receiving PTCy and its impact on post-transplant relapse is unknown. In this study we describe the kinetics of donor chimerism in patients receiving PTCy, factors predisposing to mixed donor chimerism, and the associated survival outcomes.

Validation of the 5th edition of the World Health Organization and International Consensus Classification guidelines for TP53-mutated myeloid neoplasm in an independent international cohort.

The World Health Organization (WHO-5) and International Consensus Classification (ICC) acknowledge the poor prognosis of TP53-mutated (TP53) myeloid neoplasm (MN). However, there are substantial differences between the two classifications that may lead to under- or overestimation of the prognostic risk. We retrospectively applied WHO-5 and ICC to 603 MN cases harboring TP53 (variant allele frequency, VAF ≥ 2%).

The evolving therapeutic revolution in adult acute lymphoblastic leukemia.

The past decade has witnessed remarkable advances in deciphering the pathophysiology of acute lymphoblastic leukemia (ALL) and in developing novel targeted therapies. Basic research and genomic mapping have identified new prognostic biomarkers, targets, and ALL subtypes (e.g.

Coronary Artery Calcification as a Predictor of Survival in Patients Receiving Post-transplant Cyclophosphamide for GVHD Prophylaxis.

Post-transplant Cyclophosphamide (PTCy) is becoming the new standard of care for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT). High-dose cyclophosphamide has been associated with cardiac dysfunction through multiple mechanisms. Assess if patients with evidence of coronary artery calcification (CAC) are at higher risk for non-relapse mortality (NRM) and inferior survival after receiving PTCy for GVHD prophylaxis.

Evidence-based risk stratification of myeloid neoplasms harboring TP53 mutations.

This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.

Antibody-Based and Other Novel Agents in Adult B-Cell Acute Lymphoblastic Leukemia.

Despite notable progress in managing B-cell acute lymphoblastic leukemia (B-ALL) over recent decades, particularly in pediatric cohorts where the 5-year overall survival (OS) reaches 90%, outcomes for the 10-15% with relapsed and refractory disease remain unfavorable. This disparity is further accentuated in adults, where individuals over the age of 40 years undergoing aggressive multiagent chemotherapy continue to have lower survival rates. While the adoption of pediatric-inspired treatment protocols has enhanced complete remission (CR) rates among younger adults, 20-30% of these patients experience relapse, resulting in a subsequent 5-year OS rate of 40-50%.

Hepatotoxicity induced by arsenic trioxide: clinical features, mechanisms, preventive and potential therapeutic strategies.

Arsenic trioxide (ATO) has shown substantial efficacy in the treatment of patients with acute promyelocytic leukemia, and the utilization of ATO as a potential treatment for other tumors is currently being investigated; thus, its clinical application is becoming more widespread. However, the toxicity of ATO has prevented many patients from receiving this highly beneficial treatment. The clinical features, mechanisms, and preventive measures for ATO hepatotoxicity, as well as potential curative strategies, are discussed in this review.

Clinical Outcomes and Treatment Strategies of Adult Transplant-Associated Thrombotic Microangiopathy: External Validation of Harmonizing Definitions and High-Risk Criteria.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial dysfunction syndrome observed after allogeneic hematopoietic cell transplant (alloHCT). Our aim was to externally validate the impact of high-risk features on the clinical outcomes of adult patients meeting the updated TA-TMA harmonizing criteria. Between 2005 and 2022, 99 patients were diagnosed with TA-TMA at Mayo Clinic Rochester (incidence 6.

Prevalence of cytopenia(s) and somatic variants in patients with DDX41 mutant germline predisposition syndrome.

Germline variants in DDX41 (DDX41-germline predisposition syndrome [GPS]) are associated with predisposition to haematological malignancies (HM), including lymphoid and myeloid neoplasms (MN). We retrospectively analysed the clinical and molecular features of 195 patients diagnosed and treated at Mayo Clinic with DDX41-GPS. Patients with germline DDX41 pathogenic variants (42.

Academic Community Partnership in Acute Promyelocytic Leukemia and Early Mortality: The ECOG-ACRIN EA9131 Trial.

Importance: Acute promyelocytic leukemia (APL) is an acute illness that presents with cytopenia, infections, and disseminated intravascular coagulation. Achieving remission has been shown to make a major difference in patient outcomes; however, early death rates in the first month have been as high as 30% due to acute presentation, comorbidities, the rarity of APL, and clinician inexperience.

Objective: To develop treatment strategies that would decrease estimated 1-month mortality from 30% to below 15%.

DNTT-mediated DNA damage response drives inotuzumab ozogamicin resistance in B-cell acute lymphoblastic leukemia.

Inotuzumab ozogamicin (InO) is an antibody-calicheamicin conjugate with striking efficacy in B-cell acute lymphoblastic leukemia (B-ALL). However, there is wide interpatient variability in treatment response, and the genetic basis of this variation remains largely unknown. Using a genome-wide CRISPR screen, we discovered that the loss of DNA nucleotidylexotransferase (DNTT) is a primary driver of InO resistance.

Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML.

BMT CTN (Blood and Marrow Transplant Clinical Trials Network) 1506 ("MORPHO") was a randomized study of gilteritinib compared with placebo as maintenance therapy after hematopoietic cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary end point was to determine the impact on survival of before and/or after HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD.

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.