title: Deep sequencing reveals myeloma cells in peripheral blood in majority of multiple myeloma patients.
abstract: BACKGROUND
  The evaluation of myeloma cells in multiple myeloma (MM) patients has generally been limited to the assessment of bone marrow involvement because of the sensitivity limitations of traditional minimal-residual-disease-detection methods.
  
  
  METHODS
  We developed a sequencing-based method to identify myeloma cells in bone marrow (BM) and peripheral blood (PB) samples, based on their unique immunoglobulin gene rearrangements, that can detect cancer clones at levels well below 1 in 1 million leukocytes (0.0001%). In this multisite study, we used this sequencing method to determine the fraction of patients with myeloma cells in their PB at diagnosis and posttreatment time points.
  
  
  RESULTS
  Using this sequencing approach, we detected myeloma cells in the PB in the vast majority of MM patients (44/46, 96%). We demonstrated a clear correlation (R(2) = 0.57) between myeloma clone levels in paired BM and PB samples, and noted that PB clone levels were approximately 100-fold lower than levels in BM samples. The sequencing assay demonstrated a clear sensitivity advantage in the BM compartment and at least equivalent sensitivity in the PB compared with that of monoclonal-protein results.
  
  
  CONCLUSIONS
  This study highlights the promise of a blood-based, sequencing minimal-residual-disease assay that can be used to measure MM disease burden at different time points and various disease stages.
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vij
authors.affiliation: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Mazumder
authors.affiliation: Sequenta, Inc, South San Francisco, CA.
authors.forename: Mark
authors.initials: M
authors.lastname: Klinger
authors.affiliation: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors.forename: Denise
authors.initials: D
authors.lastname: O'Dea
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Jacob
authors.initials: J
authors.lastname: Paasch
authors.affiliation: Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Martin
authors.affiliation: Sequenta, Inc, South San Francisco, CA.
authors.forename: Li
authors.initials: L
authors.lastname: Weng
authors.affiliation: Department of Medicine, New York University Langone Medical Center, New York, NY.
authors.forename: Jeesun
authors.initials: J
authors.lastname: Park
authors.affiliation: Division of Oncology, Washington University School of Medicine, St. Louis, MO.
authors.forename: Mark
authors.initials: M
authors.lastname: Fiala
authors.affiliation: Sequenta, Inc, South San Francisco, CA.
authors.forename: Malek
authors.initials: M
authors.lastname: Faham
authors.affiliation: Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA. Electronic address: wolfj@medicine.ucsf.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D015322:Gene Rearrangement, B-Lymphocyte; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D009194:Myeloma Proteins / Q000378:metabolism; D018365:Neoplasm, Residual / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D012680:Sensitivity and Specificity; D060152:V(D)J Recombination / Q000235:genetics
chemical_list: D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; D009194:Myeloma Proteins; C085016:multiple myeloma M-proteins
keywords: Circulating myeloma clones; High-throughput sequencing; Immunoglobulin gene rearrangement; Minimal residual disease; Multiple myeloma