title: Circulating CD52 and CD20 levels at end of treatment predict for progression and survival in patients with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab (FCR).
abstract: CD52 and CD20 antigens are important therapeutic targets for the monoclonal antibodies (mAbs) alemtuzumab and rituximab respectively. Circulating CD52 (cCD52) and CD20 (cCD20) have prognostic utility in lymphoid malignancies. The efficacy of mAb therapy in patients with chronic lymphocytic leukaemia (CLL) may be adversely affected by cCD52 or cCD20. In this report, blood and bone marrow (BM) cCD52 and cCD20 were measured at response assessment in previously treated (N = 235) patients with CLL who received fludarabine, cyclophosphamide, and rituximab (FCR). Univariate and multivariate statistical models evaluated correlations of pre- and response variables with progression-free (PFS) and overall survival (OS). Response variables included 1996 National Cancer Institute-Working Group (NCI-WG) response, polymerase chain reaction (PCR) for immunoglobulin heavy chain (IGHV) in BM, and cCD52 and cCD20 levels (blood and BM) at response assessment. Using multivariate analysis, response blood and BM cCD52, blood cCD20, and NCI-WG response were significant independent predictors of PFS. At the time of response assessment, BM cCD52 correlated with OS in univariate analysis. cCD52 and cCD20, therefore appear useful in predicting survival and may be important for monitoring patients following salvage FCR (fludarabine, cyclophosphamide, rituximab) therapy. These data further indicate that plasma may be a good target to evaluate for minimal residual disease using cCD52/cCD20 levels.
authors.affiliation: Department of Stem Cell Transplantation & Cellular Therapy, U.T. MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gheath
authors.initials: G
authors.lastname: Alatrash
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.forename: Taghi
authors.initials: T
authors.lastname: Manshouri
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferrajoli
authors.forename: Jan
authors.initials: J
authors.lastname: Burger
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.forename: Susan
authors.initials: S
authors.lastname: Lerner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Keating
authors.forename: William G
authors.initials: WG
authors.lastname: Wierda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000097:blood; D018951:Antigens, CD20 / Q000097:blood; D000951:Antigens, Neoplasm / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D000074301:CD52 Antigen; D003520:Cyclophosphamide / Q000008:administration & dosage; D018450:Disease Progression; D004812:Epidemiologic Methods; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000276:immunology; D011379:Prognosis; D000069283:Rituximab; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000069283:Rituximab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine