title: Predictive Value of Cytokines and Immune Activation Biomarkers in AIDS-Related Non-Hodgkin Lymphoma Treated with Rituximab plus Infusional EPOCH (AMC-034 trial).
abstract: OBJECTIVE
  The aims of this study were to determine whether pretreatment plasma levels of cytokines and immune activation-associated molecules changed following treatment for AIDS-NHL with rituximab plus infusional EPOCH, and to determine whether pretreatment levels of these molecules were associated with response to treatment and/or survival.
  
  
  METHODS
  We quantified plasma levels of B-cell activation-associated molecules (sCD27, sCD30, and sCD23) and cytokines (IL6, IL10, and CXCL13) before and after the initiation of treatment in persons with AIDS-NHL (n = 69) in the AIDS Malignancies Consortium (AMC) 034 study, which evaluated treatment of AIDS-NHL with EPOCH chemotherapy and rituximab.
  
  
  RESULTS
  Treatment resulted in decreased plasma levels of some of these molecules (CXCL13, sCD27, and sCD30), with decreased levels persisting for one year following the completion of treatment. Lower levels of CXCL13 before treatment were associated with complete responses following lymphoma therapy. Elevated levels of IL6 pretreatment were associated with decreased overall survival, whereas higher IL10 levels were associated with shorter progression-free survival (PFS), in multivariate analyses. Furthermore, patients with CXCL13 or IL6 levels higher than the median levels for the NHL group, as well as those who had detectable IL10, had lower overall survival and PFS, in Kaplan-Meier analyses.
  
  
  CONCLUSIONS
  These results indicate that CXCL13, IL6, and IL10 have significant potential as prognostic biomarkers for AIDS-NHL.
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California. Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California. UCLA AIDS Institute, Los Angeles, California. Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California.
authors.forename: Marta
authors.initials: M
authors.lastname: Epeldegui
authors.affiliation: Department of Biostatistics, College of Medicine, University of Arkansas, Little Rock, Arizona.
authors.forename: Jeannette Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Martínez
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California. UCLA AIDS Institute, Los Angeles, California.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Widney
authors.affiliation: Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California. UCLA AIDS Institute, Los Angeles, California. Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California.
authors.forename: Larry I
authors.initials: LI
authors.lastname: Magpantay
authors.affiliation: UCLA AIDS Institute, Los Angeles, California. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, California.
authors.forename: Deborah
authors.initials: D
authors.lastname: Regidor
authors.affiliation: UCLA AIDS Institute, Los Angeles, California. Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California. Department of Biostatistics, College of Medicine, University of Arkansas, Little Rock, Arizona.
authors.forename: Ronald
authors.initials: R
authors.lastname: Mitsuyasu
authors.affiliation: Division of Oncology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.affiliation: Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California. Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, Los Angeles, California. UCLA AIDS Institute, Los Angeles, California. Jonsson Comprehensive Cancer Center at UCLA, Los Angeles, California. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California. omartinez@mednet.ucla.edu.
authors.forename: Otoniel
authors.initials: O
authors.lastname: Martínez-Maza
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000276:immunology*; D003520:Cyclophosphamide / Q000627:therapeutic use; D016207:Cytokines / Q000097:blood*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D016483:Lymphoma, AIDS-Related / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D011241:Prednisone / Q000627:therapeutic use; D000069283:Rituximab / Q000627:therapeutic use*; D014750:Vincristine / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016207:Cytokines; D000069283:Rituximab; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone