Feasibility, accuracy, and usability analysis of MapAML, a first-in-class app for integrated diagnosis in acute myeloid leukemia.

Performing a comprehensive diagnosis of acute myeloid leukemia (AML) is complex and involves the integration of clinical information, bone marrow morphology, immunophenotyping, cytogenetic, and molecular analysis, which can be challenging to the general hematologist. The aim of this study was to evaluate the usability and accuracy of MapAML, a smartphone app for integrated diagnosis in AML, created to aid the hematologist in its clinical practice. App performance was evaluated in dedicated sessions, in which 21 hematologists or fellows in hematology performed an integrated diagnosis of deidentified real-world clinical AML cases, first without and posteriorly with MapAML use. Diagnosis accuracy increased after MapAML utilization, with the average score going from 7.08 without app to 8.88 with app use (on a scale from 0 to 10), representing a significant accuracy improvement (p = .002). Usability evaluation was very favorable, with 81% of users considering the app very or extremely simple to use. There was also a significant increase in confidence to perform a complete and accurate diagnosis in AML after app use, with 61.9% of the participants willing to use the app in their clinical practice. In this study, MapAML increased accuracy with excellent usability for integrated diagnosis in AML.

Molecular Characterization of a First-in-Human Clinical Response to Nimesulide in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a hematologic malignancy associated with high morbidity and mortality. Here we describe a case of a patient with AML who presented a partial response after utilization of the non-steroidal anti-inflammatory drug nimesulide. The response was characterized by complete clearance of peripheral blood blasts and an 82% decrease of bone marrow blasts associated with myeloblast differentiation. We have then shown that nimesulide induces in vitro cell death and cell cycle arrest in all AML cell lines (HL-60, THP-1, OCI-AML2, and OCI-AML3). Weighted Correlation Network Analysis (WGCNA) of serial whole-transcriptome data of cell lines treated with nimesulide revealed that the sets of genes upregulated after treatment with nimesulide were enriched for genes associated with autophagy and apoptosis, and on the other hand, the sets of downregulated genes were associated with cell cycle and RNA splicing. Serial transcriptome of bone marrow patient sample confirmed the upregulation of genes associated with autophagy after the response to nimesulide. Lastly, we demonstrated that nimesulide potentiates the cytotoxic in vitro effect of several Food and Drug Administration (FDA)-approved chemotherapy drugs used in AML, including cytarabine.

High-throughput sequencing of immunoglobulin heavy chain for minimal residual disease detection in B-lymphoblastic leukemia.

INTRODUCTION: Minimal residual disease (MRD) is a cornerstone for stratification of upfront B-lymphoblastic leukemia (B-ALL) treatment protocols to decrease relapse risk. Although its detection by flow cytometry (FC) and real-time quantitative polymerase has clinical usefulness, evidence suggests that methods with increased sensitivity could lead to improved outcomes. The aim of this study was to develop an amplicon-based assay followed by high-throughput sequencing of the immunoglobulin heavy chain variable region for MRD detection in B-ALL. METHODS: We analyzed 84 samples, 27 from diagnosis, 5 from relapse, 40 from post-treatment samples, and 12 from healthy controls. RESULTS: Our assay was able to identify more neoplastic clones at diagnosis than Sanger sequencing including incomplete DJ rearrangements. From the 40 MRD samples evaluated 21 were positive by our new approach on high-throughput sequencing assay, but only 15 of these were positive by FC. The remaining 19 were negative by the two techniques. CONCLUSION: We have developed a novel approach on high-sensitive assay for MRD detection in B-ALL, which could add clinical value in the management of patients, especially in cases negative for MRD by FC.

How I investigate minimal residual disease in acute lymphoblastic leukemia.

Minimal Residual Disease (MRD) is the most important independent prognostic factor in acute lymphoblastic leukemia (ALL) and refers to the deep level of measurable disease in cases with complete remission by conventional pathologic analysis, especially by cytomorphology. MRD can be detected by multiparametric flow cytometry, molecular approaches such as quantitative polymerase chain reaction for immunoglobulin and T-cell receptor (IG/TR) gene rearrangements or fusion genes transcript, and high-throughput sequencing for IG/TR. Despite the proven clinical usefulness in detecting MRD, these methods have differences in sensitivity, specificity, applicability, turnaround time and cost. Knowing and understanding these differences, as well as the principles and limitations of each technology, is essential to laboratory standardization and correct interpretation of MRD results in line with treatment time points, therapeutic settings, and clinical trials. Here, we review the methodological approaches to measure MRD in ALL and discuss the advantages and limitations of the most commonly used techniques.

Evaluation of NIH consensus criteria for classification of late acute and chronic GVHD.

Historically, graft-versus-host disease (GVHD) beyond 100 days after hematopoietic cell transplantation (HCT) was called chronic GVHD, even if the clinical manifestations were indistinguishable from acute GVHD. In 2005, the National Institutes of Health (NIH) sponsored a consensus conference that proposed new criteria for diagnosis and classification of chronic GVHD for clinical trials. According to the consensus criteria, clinical manifestations rather than time after transplantation should be used in clinical trials to distinguish chronic GVHD from late acute GVHD, which includes persistent, recurrent, or late-onset acute GVHD. We evaluated major outcomes according to the presence or absence of NIH criteria for chronic GVHD in a retrospective study of 740 patients diagnosed with historically defined chronic GVHD after allogeneic HCT between 1994 and 2000. The presence or absence of NIH criteria for chronic GVHD showed no statistically significant association with survival, risks of nonrelapse mortality or recurrent malignancy, or duration of systemic treatment. Antecedent late acute GVHD was associated with an increased risk of nonrelapse mortality and prolonged treatment among patients with NIH chronic GVHD. Our results support the consensus recommendation that, with appropriate stratification, clinical trials can include patients with late acute GVHD as well as those with NIH chronic GVHD.