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

Abstract

Introduction:In most laboratories, next generation sequencing (NGS) has been added without consideration for redundancy compared to conventional cytogenetics (CG).We tested a streamlined approach to genomic testing in patients with suspected myeloid and plasma cell neoplasms using next generation sequencing ("NGS first") as the primary testing modality and limiting cytogenetics (CG) to samples with morphologic abnormalities in the marrow aspirate. Methods: Based on morphologic interpretation of bone marrow aspirate and flow cytometry, samples were triaged into four groups: (a) Samples with dysplasia or excess blasts had both NGS and karyotyping; (b) Samples without excess blasts or dysplasia had NGS only; (c) Repeat samples with previous NGS and/or CG studies were not retested; (d) Samples for suspected myeloma with less than 5% plasma cell had CG testing cancelled. Results: Seven hundred eleven adult bone marrow (BM) samples met the study criteria. The NGS first algorithm eliminated CG testing in 229/303 (75.6%) of patients, primarily by reducing repeat testing. Potential cost avoided was approximately $124 000 per annum. Hematologists overruled the triage comment in only 11/303 (3.6%) cases requesting CG testing for a specific indication. Conclusions: Utilizing NGS as the primary genomic testing modality NGS was feasible and well accepted, reducing over three quarters of all CG requests and improving the financial case for adoption of NGS. Key factors for the success of this study were collaboration of clinical and genomic diagnostic teams in developing the algorithm, rapid turnaround time for BM interpretation for triage, and communication between laboratories.

Finding Goldilocks: Choosing Wisely Together in Hematology/Oncology

“…One feature of our approach, which we found encouraged buy-in from clinicians, was allowing the MRP to request ad hoc testing beyond SOPs in specific cases in discussion with the laboratory on the basis of clinical judgment. 4 Facilitating shared decision making between the clinic and laboratory—Choosing Wisely Together—requires commitment from stakeholders from bench to bedside to develop and adhere to consensus algorithms, along with an eye toward continual improvement and willingness to change as new evidence emerges.…”

“…At our center, we successfully developed and implemented a similar strategy for patients with suspected myeloid neoplasms using consensus diagnostic algorithms and morphology/flow cytometry-based triage. [3][4][5] In addition, we reduced low-value, redundant testing through an NGS first approach, limiting cytogenetics to cases with overt dysplasia. 4 From our experience, a major advantage of this shared decision-making approach is that it helps overcome the limitations of each group's siloed perspective to provide a more comprehensive diagnostic picture.…”

“…[3][4][5] In addition, we reduced low-value, redundant testing through an NGS first approach, limiting cytogenetics to cases with overt dysplasia. 4 From our experience, a major advantage of this shared decision-making approach is that it helps overcome the limitations of each group's siloed perspective to provide a more comprehensive diagnostic picture.…”