title: B cells with high side scatter parameter by flow cytometry correlate with inferior survival in diffuse large B-cell lymphoma.
abstract: Despite advances in the understanding of diffuse large B-cell lymphoma (DLBCL) biology, only the clinically based International Prognostic Index (IPI) is used routinely for risk stratification at diagnosis. To find novel prognostic markers, we analyzed flow cytometric data from 229 diagnostic DLBCL samples using an automated multiparameter data analysis approach developed in our laboratory. By using the developed automated data analysis pipeline, we identified 71 of 229 cases as having more than 35% B cells with a high side scatter (SSC) profile, a parameter reflecting internal cellular complexity. This high SSC B-cell feature was associated with inferior overall and progression-free survival (P = .001 and P = .01, respectively) and remained a significant predictor of overall survival in multivariate Cox regression analysis (IPI, P = .001; high SSC, P = .004; rituximab, P = .53). This study suggests that high SSC among B cells may serve as a useful biomarker to identify patients with DLBCL at high risk for relapse. This is of particular interest because this biomarker is readily available in most clinical laboratories without significant alteration to existing routine diagnostic strategies or incurring additional costs.
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Bashashati
authors.forename: Nathalie A
authors.initials: NA
authors.lastname: Johnson
authors.forename: Alireza Hadj
authors.initials: AH
authors.lastname: Khodabakhshi
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Whiteside
authors.forename: Habil
authors.initials: H
authors.lastname: Zare
authors.forename: David W
authors.initials: DW
authors.lastname: Scott
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lo
authors.forename: Raphael
authors.initials: R
authors.lastname: Gottardo
authors.forename: Fiona S L
authors.initials: FS
authors.lastname: Brinkman
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.forename: Graham W
authors.initials: GW
authors.lastname: Slack
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Weng
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Brinkman
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000276:immunology / Q000401:mortality* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D000069283:Rituximab; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone