title: Do biologic parameters affect the time to first treatment of clinical monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia Rai stage 0? Results of a prospective analysis.
abstract: BACKGROUND
  We investigated the clinical relevance of classic and new prognostic markers, immunoglobulin heavy-chain variable (IGHV) gene mutational status, and chromosomal abnormalities in clinical monoclonal B lymphocytosis (cMBL) compared with chronic lymphocytic leukemia (CLL) Rai stage 0.
  
  
  METHODS
  We analyzed the clinical outcomes in terms of the time to the first treatment (TTFT) of a prospective cohort, including 125 patients with cMBL and 197 patients with CLL Rai stage 0.
  
  
  RESULTS
  In the overall patient population, prognostic parameters such as IGHV gene mutational status (P < .0001), CD38 expression (P < .0001), 70-kDa zeta-associated protein (ZAP-70) expression (P < .0001), and cytogenetic abnormalities (P = .01) predicted for TTFT on univariate analysis. IGHV gene identity was significant on multivariate analysis (P < .0001), regardless of the B-cell cutoff (5.0 or 10 × 10(9) B cells/L). A prognostic stratification using the combination of IGHV mutational status and absolute B-cell lymphocytosis identified 3 different groups that were significantly different with respect to the TTFT (P < .0001).
  
  
  CONCLUSIONS
  In the present series of patients with cMBL and CLL Rai stage 0, we have confirmed that IGHV mutation status appeared to be the best predictor of TTFT. In addition, when associated with the B-cell count, IGHV mutational status might help to better stratify patients into more precise subgroups.
authors.affiliation: Department of Oncology-Hematology, Pugliese-Ciaccio Hospital Center, Catanzaro, Italy. Electronic address: smolica@libero.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Molica
authors.affiliation: Biostatistics Unit, Regina Elena Institute for Cancer Research and Treatment, Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Department of Oncology-Hematology, Pugliese-Ciaccio Hospital Center, Catanzaro, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Levato
authors.affiliation: Complex Operative Hematology Unit, Cosenza Hospital Center, Cosenza, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Gentile
authors.affiliation: Department of Oncology-Hematology, Pugliese-Ciaccio Hospital Center, Catanzaro, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Mirabelli
authors.affiliation: Complex Operative Hematology Unit, Cosenza Hospital Center, Cosenza, Italy.
authors.forename: Fortunato
authors.initials: F
authors.lastname: Morabito
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D015415:Biomarkers / Q000378:metabolism; D060965:Clonal Evolution / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D007143:Immunoglobulin Heavy Chains; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1
keywords: CLL; IGHV; Prognosis; TTFT; cMBL