Ultra-Rapid Reporting of GENomic Targets (URGENTseq): Clinical Next-Generation Sequencing Results within 48 Hours of Sample Collection.

Next-generation sequencing (NGS)-based mutation panels profile multiple genes simultaneously, allowing the reporting of numerous genes while saving labor and resources. However, one drawback of using NGS is that the turnaround time is often longer than conventional single gene tests. This delay can be problematic if molecular results are required to guide therapy in patients with clinically aggressive diseases, such as acute myeloid leukemia. To overcome this limitation, we developed a novel custom platform designated as Ultra-rapid Reporting of GENomic Targets (URGENTseq), an integrated solution that includes workflow optimization and an innovative custom bioinformatics pipeline to provide targeted NGS results on fresh peripheral blood and bone marrow samples within an actionable time period. URGENTseq was validated for clinical use by determining mutant allelic frequency and minimum coverage in silico to achieve 100% concordance for all positive and negative calls between the URGENTseq and conventional sequencing approach. URGENTseq enables the reporting of selected genes useful for immediate diagnosis (CALR, CSF3R, JAK2, KRAS, MPL, NPM1, NRAS, SF3B1) and treatment decisions (IDH1, IDH2) in hematologic malignancies within 48 hours of specimen collection. In addition, we summarize the molecular findings of the first 272 clinical test results performed using the URGENTseq platform.

Bone marrow core biopsy in 508 consecutive patients with chronic myeloid leukemia: Assessment of potential value.

BACKGROUND: The diagnosis of chronic myeloid leukemia (CML) is based on characteristic clinical and laboratory findings and the presence of BCR/ABL1 in the blood and/or bone marrow (BM). The utility of BM core biopsy in the workup of patients with CML has been questioned. METHODS: The potential added value of BM biopsy versus aspiration in the workup of a single-institution series of 508 patients with CML at their initial presentation was systematically assessed. BM biopsy was considered essential when it was needed to establish the disease phase, often because blast counts derived from aspirate smears were misleading because the biopsy specimen was more representative of the disease. BM biopsy was considered helpful if it was needed for other nonessential reasons. RESULTS: In 127 patients (25%), BM biopsy was either essential (109 patients) or helpful (18 patients). Patients with accelerated-phase (AP) or blast-phase (BP) disease often required a biopsy related to essential reasons. High-grade myelofibrosis (MF) was more frequent in patients with AP/BP disease than patients with chronic-phase disease (P = .0005), and the identification of BP disease required a BM biopsy assessment in 75% of the patients (P = .001). A follow-up BM evaluation more often yielded inadequate aspirates in patients with inadequate BM aspirates at the time of their initial diagnosis. CONCLUSIONS: BM core biopsy remains valuable in the workup of 25% of patients with CML because it facilitates identification of the disease phase or MF. The initial grade of MF is associated with the disease stage and outcome after therapy. BM biopsy is, therefore, indicated for patients with CML who have AP/BP disease or other findings suggestive of progressive disease.