Dataset Information

Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations.

ABSTRACT:

Background

Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed.

Methods

We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM.

Results

AML patients with EM presented with significantly higher counts of white blood cells (p < 0.0001), peripheral blood blasts (p < 0.0001), bone marrow blasts (p = 0.019), and LDH (p < 0.0001). Regarding molecular genetics, EM AML was associated with mutations of NPM1 (OR: 1.66, p < 0.001), FLT3-ITD (OR: 1.72, p < 0.001) and PTPN11 (OR: 2.46, p < 0.001). With regard to clinical outcomes, EM AML patients were less likely to achieve complete remissions (OR: 0.62, p = 0.004), and had a higher early death rate (OR: 2.23, p = 0.003). Multivariable analysis revealed EM as an independent risk factor for reduced overall survival (hazard ratio [HR]: 1.43, p < 0.001), however, for patients who received allogeneic hematopoietic cell transplantation (HCT) survival did not differ. For patients bearing EM AML, multivariable analysis unveiled mutated TP53 and IKZF1 as independent risk factors for reduced event-free (HR: 4.45, p < 0.001, and HR: 2.05, p = 0.044, respectively) and overall survival (HR: 2.48, p = 0.026, and HR: 2.63, p = 0.008, respectively).

Conclusion

Our analysis represents one of the largest cohorts of EM AML and establishes key molecular markers linked to EM, providing new evidence that EM is associated with adverse risk in AML and may warrant allogeneic HCT in eligible patients with EM.

SUBMITTER: Eckardt JN

PROVIDER: S-EPMC9107142 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations.

Eckardt Jan-Niklas JN Stölzel Friedrich F Kunadt Desiree D Röllig Christoph C Stasik Sebastian S Wagenführ Lisa L Jöhrens Korinna K Kuithan Friederike F Krämer Alwin A Scholl Sebastian S Hochhaus Andreas A Crysandt Martina M Brümmendorf Tim H TH Naumann Ralph R Steffen Björn B Kunzmann Volker V Einsele Hermann H Schaich Markus M Burchert Andreas A Neubauer Andreas A Schäfer-Eckart Kerstin K Schliemann Christoph C Krause Stefan W SW Herbst Regina R Hänel Mathias M Hanoun Maher M Kaiser Ulrich U Kaufmann Martin M Rácil Zdenek Z Mayer Jiri J Kroschinsky Frank F Berdel Wolfgang E WE Ehninger Gerhard G Serve Hubert H Müller-Tidow Carsten C Platzbecker Uwe U Baldus Claudia D CD Schetelig Johannes J Bornhäuser Martin M Thiede Christian C Middeke Jan Moritz JM

Journal of hematology & oncology 20220513 1

<h4>Background</h4>Extramedullary manifestations (EM) are rare in acute myeloid leukemia (AML) and their impact on clinical outcomes is controversially discussed.<h4>Methods</h4>We retrospectively analyzed a large multi-center cohort of 1583 newly diagnosed AML patients, of whom 225 (14.21%) had EM.<h4>Results</h4>AML patients with EM presented with significantly higher counts of white blood cells (p < 0.0001), peripheral blood blasts (p < 0.0001), bone marrow blasts (p = 0.019), and LDH (p < 0. ...[more]

PMID: 35562747

Similar Datasets

Project description:Acute myeloid leukemia (AML) is an infrequent disease, and it is associated with high morbidity and mortality. It harbors a unique configuration of cytogenetic abnormalities and molecular mutations that can be detected using microscopic and molecular methods respectively. These genetic tests are core elements of diagnosis and prognostication in high-income countries. They are routinely incorporated in clinical decision making, allowing for the individualization of therapy. However, these tests are largely inaccessible to most patients in Kenya and therefore no data has been reported on this group of patients. The main purpose of this study is to describe the cytogenetic and molecular abnormalities of acute myeloid leukemia patients seen at the hemato-oncology unit of Kenyatta National Hospital. A cross-sectional descriptive study was carried out over a 3-month period on ten patients with a diagnosis of AML. Social demographics and clinical data were collected through a study proforma. A peripheral blood sample was collected for conventional metaphase G-banding technique and next generation sequencing. Particularly, targeted DNA sequencing (Illumina myeloid panel) and whole exome sequencing (WES) were performed. Cytogenetic analysis failed in 10/10 cases. Targeted sequencing was successfully obtained in 8 cases, whereas WES in 7. Cytogenetic studies yielded no results. There were 20 mutations detected across 10 commonly mutated genes. All patients had at least one clinically relevant mutation. Based on ELN criteria, NGS identified three patients with high-risk mutations, affecting TP53 (n = 2) and RUNX1 (n = 1). One patient was classified as favorable (PML-RARA) while 4 were standard risk. However, WT1 mutations associated with unfavorable prognosis were recorded in additional 2 cases. WES showed concordant results with targeted sequencing while unveiling more mutations that warrant further attention. In conclusion, we provide the first molecular profiling study of AML patients in Kenya including application of advanced next generation sequencing technologies, highlighting current limitations of AML diagnostics and treatment while confirming the relevance of NGS in AML characterization.

Dataset Information

Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations.

Background

Methods

Results

Conclusion

Publications

Molecular profiling and clinical implications of patients with acute myeloid leukemia and extramedullary manifestations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets