title: Next-Generation Sequencing in Adult B Cell Acute Lymphoblastic Leukemia Patients.
abstract: We used next-generation sequencing (NGS) of the immunoglobulin genes to evaluate residual disease in 153 specimens from 32 patients with adult B cell acute lymphoblastic leukemia enrolled in a single multicenter study. The sequencing results were compared with multiparameter flow cytometry (MFC) data in 66 specimens (25 patients) analyzed by both methods. There was a strong concordance (82%) between the methods in the qualitative determination of the presence of disease. However, in 17% of cases, leukemia was detected by sequencing but not by MFC. In 54 bone marrow (BM) and peripheral blood (PB) paired specimens, the burden of leukemia detected by NGS was lower in PB than in BM, although it was still detectable in 68% of the 28 paired specimens with positive BM. Lastly, patients without disease detected by NGS or MFC had a 5-year relapse free survival of > 80%. The results suggest that residual disease detection by immunoglobulin gene sequencing is an extremely sensitive technique and may identify patients that might benefit from transplantation. Moreover, the increased sensitivity of the method may allow frequent peripheral blood testing to supplement marrow sampling to measure disease response.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. Electronic address: osala@fredhutch.org.
authors.forename: Olga
authors.initials: O
authors.lastname: Sala Torra
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; SWOG Statistical Center, Seattle, Washington.
authors.forename: Megan
authors.initials: M
authors.lastname: Othus
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington.
authors.forename: David W
authors.initials: DW
authors.lastname: Williamson
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, Washington.
authors.forename: Brent
authors.initials: B
authors.lastname: Wood
authors.affiliation: Adaptive Biotechnologies, Seattle, Washington.
authors.forename: Ilan
authors.initials: I
authors.lastname: Kirsch
authors.affiliation: Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Harlan
authors.initials: H
authors.lastname: Robins
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Lan
authors.initials: L
authors.lastname: Beppu
authors.affiliation: Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, California.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: O'Donnell
authors.affiliation: Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Medical Center, Duarte, California.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Jerald P
authors.initials: JP
authors.lastname: Radich
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D005434:Flow Cytometry; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics*; D000072916:Peripheral Blood Stem Cells / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult
chemical_list: D007136:Immunoglobulins
keywords: Acute lymphoblastic leukemia; Minimal residual disease