Improving risk stratification for 2022 European LeukemiaNet favorable-risk patients with acute myeloid leukemia.

Assignment of patients diagnosed with acute myeloid leukemia (AML) to the 2022 European LeukemiaNet (ELN) favorable genetic risk group has important clinical implications, as allogeneic stem cell transplantation in first complete remission (CR) is not advised due to a relatively good outcome of patients receiving chemotherapy alone and transplant-associated mortality. However, not all favorable genetic risk patients experience long-term relapse-free survival (RFS), making recognition of patients who would most likely be cured of high importance. We analyzed 297 patients aged <60 years with AML classified as 2022 ELN favorable genetic risk who achieved a CR and had RNA sequencing (RNA-seq) and gene mutation data from diagnostic samples available (Alliance trial A152010).

[Recurrent hemolysis and iron overload of unclear origin].

The case of a 33-year-old male with recurrent icterus and hemolysis since childhood that was long mistaken for Gilbert disease is presented. Subsequently, the patient also developed splenomegaly and gallstones together with iron overload. Genetic testing revealed the diagnosis of hereditary xerocytosis, which is an erythrocyte membrane disorder causing recurrent hemolysis.

Identifying long-term survivors and those at higher or lower risk of relapse among patients with cytogenetically normal acute myeloid leukemia using a high-dimensional mixture cure model.

Patients with cytogenetically normal acute myeloid leukemia (CN-AML) may harbor prognostically relevant gene mutations and thus be categorized into one of the three 2022 European LeukemiaNet (ELN) genetic-risk groups. Nevertheless, there remains heterogeneity with respect to relapse-free survival (RFS) within these genetic-risk groups. Our training set included 306 adults on Alliance for Clinical Trials in Oncology studies with de novo CN-AML aged < 60 years who achieved a complete remission and for whom centrally reviewed cytogenetics, RNA-sequencing, and gene mutation data from diagnostic samples were available (Alliance trial A152010).

Prognostic impact of CEBPA mutational subgroups in adult AML.

Despite recent refinements in the diagnostic and prognostic assessment of CEBPA mutations in AML, several questions remain open, i.e. implications of different types of basic region leucin zipper (bZIP) mutations, the role of co-mutations and the allelic state.

Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG).

Clinical outcome of patients with acute myeloid leukemia (AML) is associated with demographic and genetic features. Although the associations of acquired genetic alterations with patients' sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols.

[Artificial Intelligence for computer-aided leukemia diagnostics].

The manual examination of blood and bone marrow specimens for leukemia patients is time-consuming and limited by intra- and inter-observer variance. The development of AI algorithms for leukemia diagnostics requires high-quality sample digitization and reliable annotation of large datasets. Deep learning-based algorithms using these datasets attain human-level performance for some well-defined, clinically relevant questions such as the blast character of cells.

Impact of extramedullary disease in AML patients undergoing sequential RIC for HLA-matched transplantation: occurrence, risk factors, relapse patterns, and outcome.

We sought to evaluate the role of extramedullary disease (EMD) in sequential RIC retrospectively analyzing data of 144 high-risk AML patients undergoing HLA-matched transplantation. Median long-term follow-up was 11.6 years.

Unsupervised meta-clustering identifies risk clusters in acute myeloid leukemia based on clinical and genetic profiles.

Background: Increasingly large and complex biomedical data sets challenge conventional hypothesis-driven analytical approaches, however, data-driven unsupervised learning can detect inherent patterns in such data sets.

Methods: While unsupervised analysis in the medical literature commonly only utilizes a single clustering algorithm for a given data set, we developed a large-scale model with 605 different combinations of target dimensionalities as well as transformation and clustering algorithms and subsequent meta-clustering of individual results. With this model, we investigated a large cohort of 1383 patients from 59 centers in Germany with newly diagnosed acute myeloid leukemia for whom 212 clinical, laboratory, cytogenetic and molecular genetic parameters were available.

CD33 BiTE molecule-mediated immune synapse formation and subsequent T-cell activation is determined by the expression profile of activating and inhibitory checkpoint molecules on AML cells.

Bispecific T-cell engager (BiTE) molecules recruit T cells to cancer cells through CD3ε binding, independently of T-cell receptor (TCR) specificity. Whereas physiological T-cell activation is dependent on signal 1 (TCR engagement) and signal 2 (co-stimulation), BiTE molecule-mediated T-cell activation occurs without additional co-stimulation. As co-stimulatory and inhibitory molecules modulate the strength and nature of T-cell responses, we studied the impact of the expression profile of those molecules on target cells for BiTE molecule-mediated T-cell activation in the context of acute myeloid leukemia (AML).

Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia.

The revised 2022 European LeukemiaNet (ELN) AML risk stratification system requires validation in large, homogeneously treated cohorts. We studied 1118 newly diagnosed AML patients (median age, 58 years; range, 18-86 years) who received cytarabine-based induction chemotherapy between 1999 and 2012 and compared ELN-2022 to the previous ELN-2017 risk classification. Key findings were validated in a cohort of 1160 mostly younger patients.

Mechanosensing via a GpIIb/Src/14-3-3ζ axis critically regulates platelet migration in vascular inflammation.

Platelets are not only the first responders in thrombosis and hemostasis but also central players in inflammation. Compared with platelets recruited to thrombi, immune-responsive platelets use distinct effector functions including actin-related protein complex 2/3-dependent migration along adhesive substrate gradients (haptotaxis), which prevents inflammatory bleeding and contributes to host defense. How platelet migration in this context is regulated on a cellular level is incompletely understood.

[Infections in patients with acute myeloid leukemia].

Infections represent one of the most frequent complications during therapy of acute myeloid leukemia (AML). In addition to associated prolonged phases of neutropenia, damage to the mucosal barrier by cytotoxic agents favors infections caused by endogenous pathogens. The source often remains unknown with bacteremia being the most common evidence of infection.

Explainable AI identifies diagnostic cells of genetic AML subtypes.

Explainable AI is deemed essential for clinical applications as it allows rationalizing model predictions, helping to build trust between clinicians and automated decision support tools. We developed an inherently explainable AI model for the classification of acute myeloid leukemia subtypes from blood smears and found that high-attention cells identified by the model coincide with those labeled as diagnostically relevant by human experts. Based on over 80,000 single white blood cell images from digitized blood smears of 129 patients diagnosed with one of four WHO-defined genetic AML subtypes and 60 healthy controls, we trained SCEMILA, a single-cell based explainable multiple instance learning algorithm.

Allogeneic Hematopoietic Cell Transplantation vs Standard Consolidation Chemotherapy in Patients With Intermediate-Risk Acute Myeloid Leukemia: A Randomized Clinical Trial.

Importance: The ideal postremission strategy in intermediate-risk acute myeloid leukemia (AML) in first complete remission (CR) has been a matter of debate.

Objective: To explore the optimal therapy for patients with intermediate-risk AML after first complete remission.

Design, Settings, And Participants: This investigator-initiated, open-label, 2-armed, phase 3 randomized clinical trial assessed patients at 16 hospitals in Germany from February 2, 2011, until July 1, 2018.

AGIHO guideline on evidence-based management of COVID-19 in cancer patients: 2022 update on vaccination, pharmacological prophylaxis and therapy in light of the omicron variants.

The novel coronavirus SARS-CoV-2 and the associated infectious disease COVID-19 pose a significant challenge to healthcare systems worldwide. Patients with cancer have been identified as a high-risk population for severe infections, rendering prophylaxis and treatment strategies for these patients particularly important. Rapidly evolving clinical research, resulting in the recent advent of various vaccines and therapeutic agents against COVID-19, offers new options to improve care and protection of cancer patients.

A randomized phase 2 trial of nintedanib and low-dose cytarabine in elderly patients with acute myeloid leukemia ineligible for intensive chemotherapy.

We investigated the safety and efficacy of nintedanib added to low-dose cytarabine (LDAC) in a phase 1/2 study in patients 60 years or older with newly diagnosed or relapsed/refractory (r/r) AML ineligible for intensive chemotherapy. The results of the dose-finding phase 1 part have been previously published. Patients were randomized 1:1 to LDAC plus nintedanib or LDAC plus placebo stratified by AML status (newly diagnosed vs r/r).

Molecular profiling of patients with cytogenetically normal acute myeloid leukemia and hyperleukocytosis.

Background: Acute myeloid leukemia (AML) with initial hyperleukocytosis is associated with high early mortality and a poor prognosis. The aims of this study were to delineate the underlying molecular landscape in the largest cytogenetic risk group, cytogenetically normal acute myeloid leukemia (CN-AML), and to assess the prognostic relevance of recurrent mutations in the context of hyperleukocytosis and clinical risk factors.

Methods: The authors performed a targeted sequencing of 49 recurrently mutated genes in 56 patients with newly diagnosed CN-AML and initial hyperleukocytosis of ≥100 G/L treated in the AMLCG99 study.