title: Combinations of ZAP-70, CD38 and IGHV mutational status as predictors of time to first treatment in CLL.
abstract: ZAP-70, CD38 and IGHV mutations have all been reported to have prognostic impact in chronic lymphocytic leukemia (CLL), both individually and in paired combinations. We aimed to determine whether the combination of all three factors provided more refined prognostic information concerning the treatment-free interval (TFI) from diagnosis. ZAP-70, CD38 and IGHV mutations were evaluated in 142 patients. Combining all three factors, the ZAP-70-/CD38-/Mutated group showed the longest median TFI (62 months, n = 37), ZAP-70+/CD38+/Unmutated cases the shortest (11 months, n = 37) and cases discordant for > or = 1 factor, an intermediate TFI (27 months, n = 68) (p = 0.006). Analysis of discordant cases revealed values that were otherwise masked when measuring single prognostic factors. The presence or absence of cytogenetic abnormalities did not explain the variability among discordant cases. Simultaneous analysis of ZAP-70, CD38 and IGHV mutations in CLL provides more discriminatory prediction of TFI than any factor alone.
authors.affiliation: Section of Haemato-Oncology, The Institute of Cancer Research, Sutton, Surrey, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Morilla
authors.forename: David
authors.initials: D
authors.lastname: Gonzalez de Castro
authors.forename: Ilaria
authors.initials: I
authors.lastname: Del Giudice
authors.forename: Nnenna
authors.initials: N
authors.lastname: Osuji
authors.forename: Monica
authors.initials: M
authors.lastname: Else
authors.forename: Ricardo
authors.initials: R
authors.lastname: Morilla
authors.forename: Vasantha
authors.initials: V
authors.lastname: Brito Babapulle
authors.forename: Hannah
authors.initials: H
authors.lastname: Rudenko
authors.forename: Estella
authors.initials: E
authors.lastname: Matutes
authors.forename: Claire
authors.initials: C
authors.lastname: Dearden
authors.forename: Daniel
authors.initials: D
authors.lastname: Catovsky
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D011379:Prognosis; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics*
chemical_list: D015415:Biomarkers; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051997:ADP-ribosyl Cyclase 1