Concordance of Peripheral Blood and Bone Marrow Next-Generation Sequencing in Hematologic Neoplasms

Abstract

Objective. Mutational analysis by next-generation sequencing (NGS) obtained by peripheral blood NGS has been of clinical interest to use as a minimally invasive screening tool. Our study evaluates the correlation between NGS results on peripheral blood and bone marrow in hematolymphoid disease. Method. We evaluated patients who had NGS for presumed hematologic malignancy performed on peripheral blood and bone marrow within a 1-year interval of each other. We excluded cases in which chemotherapy or bone marrow transplant occurred in the interval between the two tests. The concordance across peripheral blood and bone marrow NGS results was assessed by kappa coefficient analysis. Results. A total of 163 patients were studied. Concordance of peripheral blood and bone marrow NGS found in 150 patients (92.0%) with a kappa coefficient of 0.794 (kappa standard error 0.054) and P value for testing kappa <0.0001. Myeloid neoplasms showed concordant results in 77/78 cases (98.7%) with a kappa coefficient of 0.916. Lymphoid neoplasms showed concordant results in 26/31 cases (83.9%) with a kappa coefficient of 0.599. Nonneoplastic cases showed concordant results in 47/54 cases (87.0%) with a kappa coefficient of 0.743. Conclusion. Peripheral blood NGS is a reliable tool for mutational analysis and provides a less invasive method for screening and monitoring of the molecular profile.

High concordance of clone detection between peripheral blood and bone marrow by targeted next‐generation sequencing—A pilot study in patients with MDS

“…In this study we support and extend previous studies from the literature 15 by showing a high concordance of mutational profiles between BM and PB. Our findings indicate that PB constitutes a valuable and representative substitute for BMderived mutational profiling, in particular when considering sequential analyses and clonal evolution of MDS during therapy.…”

Capture‐based targeted sequencing using a T‐cell control in myeloid malignancies and idiopathic cytopenias

“…Although previous studies have compared sequencing of peripheral blood and bone marrow, this is the first study that used material acquired at the same timepoint, and employed a capture-based panel in combination with lymphocyte depletion to enrich for myeloid cells (to reduce the risk of a false negative where patients have profound neutropenia/monocytopenia). [32][33][34] Although the investigation of cytopenias could start with the sequencing of DPB, there is a danger of missing some cases of MDS as not all bear mutations that are detectable by current approaches. 28 The main benefits of the paired approach were both reliable identification and interpretation of germline variants and a reduction of analysis time, as the assessment of VUS and the identification of artefacts, misalignments and errors were greatly simplified.…”

Myeloid NGS Analyses of Paired Samples from Bone Marrow and Peripheral Blood Yield Concordant Results: A Prospective Cohort Analysis of the AGMT Study Group

“…Some research groups used targeted NGS approaches to assess whether peripheral blood may be an acceptable alternative sample to bone marrow in patients with hematologic neoplasms [ 40 , 41 , 42 , 43 ] ( Table 1 ). These studies reported on 16–183 paired peripheral blood and bone marrow samples and detected a complete concordance of 69–97%.…”

“…These studies reported on 16–183 paired peripheral blood and bone marrow samples and detected a complete concordance of 69–97%. Four of these seven studies either included or were exclusively performed in patients with lymphoid neoplasms [ 40 , 42 , 44 , 45 ], five did not report how many days were allowed between the peripheral blood and bone marrow samples, two reported up to 334 days between the sampling, and the sensitivity of the NGS analyses and/or the mean (min–max) coverage were rarely reported. Nevertheless, these important studies underscore the relevance and the real-world clinical need to be able to diagnose and monitor treatment response without repeated bone marrow evaluations.…”

“…Hence, a real-world clinical need exists to be able to use an alternative or surrogate sample, to be able to obtain information on the mutational status of a patient’s disease. In this regard, research groups around the world have assessed whether the genetic information required for an integrated diagnosis and/or treatment monitoring may also be obtained from analysis of the peripheral blood of patients with various hematologic malignancies ( Table 1 and Table S1 ) [ 20 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ].…”