Clinical value of next‐generation sequencing compared to cytogenetics in patients with suspected myelodysplastic syndrome

Abstract

Summary Next‐generation sequencing (NGS) increasingly influences diagnosis, prognosis and management of myelodysplastic syndrome (MDS). In addition to marrow morphology and flow cytometry, our institution performs cytogenetics (CG) and NGS‐based testing routinely in patients with suspected MDS. We evaluated the relative value of NGS in the assessment of patients with suspected MDS. We initially compared the diagnostic and prognostic information derived from CG and NGS in 134 patients. NGS enhanced the diagnostic yield compared to CG for clonal myeloid disorders (sensitivity 77% vs. 42·2%; specificity 90·2% vs. 78%; positive predictive value 92·8% vs. 76%; and negative predictive value 70·8% vs. 45·5%). The identification of poor prognosis mutations by NGS altered risk category in 27/39 (69·2%) patients with MDS with good/intermediate risk CG. Subsequently, we prospectively evaluated 70 patients with suspected MDS using an ‘NGS‐first approach’ with CG restricted to samples with morphological abnormalities. We rarely identified mutations or CG abnormalities in patients without dysplastic features. NGS has a superior diagnostic performance compared to CG in patients with suspected MDS. We estimate that by using an ‘NGS‐first approach’ we could reduce karyotyping by approximately 30%.

Reducing cytogenetic testing in the era of next generation sequencing: Are we choosing wisely?

“…We also validated an "NGS first" testing algorithm to limit CG testing to cases with overt dysplastic changes on morphologic examination of the BM aspirate (BMA) or FCM. 5 In MDS, we and others demonstrated that NGS defined genetic abnormalities in more patients compared to CG. [5][6][7] Importantly, mutations or CG abnormalities were rarely detected in patients without dysplastic features or increased blasts.…”

“…5 In MDS, we and others demonstrated that NGS defined genetic abnormalities in more patients compared to CG. [5][6][7] Importantly, mutations or CG abnormalities were rarely detected in patients without dysplastic features or increased blasts. Likewise, Duncavage et al recently implemented a streamlined whole-genome sequencing (WGS) approach to assess patients with myeloid cancers.…”

“…At our institution, most patients with suspected hematologic malignancy, including myelodysplastic syndromes (MDS), acute leukemia (AL), or myeloproliferative neoplasms (MPNs), have both conventional CG and NGS routinely ordered in addition to bone marrow (BM) morphology and flow cytometry (FCM). In previous studies, we tested a myeloid NGS panel in patients with suspected hematologic malignancy 4 and compared the result obtained by NGS with traditional CG karyotyping, 5 which demonstrated that NGS had a higher diagnostic and prognostic yield than CG in patients with MDS. We also validated an "NGS first" testing algorithm to limit CG testing to cases with overt dysplastic changes on morphologic examination of the BM aspirate (BMA) or FCM.…”

Chronic myeloid leukemia-from the Philadelphia chromosome to specific target drugs: A literature review

“…This process is used in most medical centers and clinical trials, especially to detect additional chromosome abnormalities and clonal evolution. Unfortunately, karyotyping is still laborious, expensive and time consuming[ 50 , 51 ].…”

Incorporation of somatic panels for the detection of haematopoietic transformation in children and young adults with leukaemia predisposition syndromes and with acquired cytopenias

“…Thus, for some patients, molecular studies were more sensitive for clonal evolution than cytogenetic and FISH studies, concurring with a recent study of adults with cytopenias/suspected MDS. 39 The role of somatic panels in the diagnosis and treatment of patients with congenital or inherited cytopenias…”