title: Clinical tumor cell distribution pattern is a prognostically relevant parameter in patients with B-cell chronic lymphocytic leukemia.
abstract: OBJECTIVE
  B-cell chronic lymphocytic leukemia (B-CLL) cells are variably distributed among the major lymphoid compartments contributing to the heterogeneous clinical presentation and course of this disease. In order to evaluate this variable distribution we propose a model for its clinical assessment.
  
  
  METHODS
  We introduce the model for tumor distribution (TD) assessment based on TTM scoring system, where TD value represents percentage of total tumor mass infiltrating peripheral blood and bone marrow (TD=TM(1)/TTM). TD in B-CLL can be categorized into 3 subgroups: pure leukemia if TD=100%, predominantly leukemia if TD=50-99% and predominantly lymphoma TD<50%.
  
  
  RESULTS
  Among 341 B-CLL patients there were 22.6%, 55.1%, 22.3%, pure leukemia, predominantly leukemia and predominantly lymphoma cases, respectively. TD parameter was strongly associated in univariate analysis with TTM size, Rai and Binet stages, spleen size and beta(2) microglobulin. TD was associated with response to therapy and survival, with higher TD values translated into higher response rates and longer survival. However, in univariate and multivariate Cox analysis TD displayed much stronger relationship with prognosis in female patients, where it is the strongest independent predictor of survival along with age and Binet stage.
  
  
  CONCLUSIONS
  TD, a quantitative and simple clinical parameter, easily assessed in all patients, offers a reliable tool for evaluation of tumor cell distribution in B-CLL. It has independent and strong prognostic power in females, as opposed to males, possibly unmasking important, yet unrecognized, biological difference in B-CLL patients.
authors.affiliation: Department of Internal Medicine, Merkur University Hospital, Zagreb, Croatia. bjaksic@mef.hr
authors.forename: O
authors.initials: O
authors.lastname: Jaksic
authors.forename: R
authors.initials: R
authors.lastname: Vrhovac
authors.forename: R
authors.initials: R
authors.lastname: Kusec
authors.forename: M M
authors.initials: MM
authors.lastname: Kardum
authors.forename: V
authors.initials: V
authors.lastname: Pandzic-Jaksic
authors.forename: I
authors.initials: I
authors.lastname: Kardum-Skelin
authors.forename: A
authors.initials: A
authors.lastname: Planinc-Peraica
authors.forename: F
authors.initials: F
authors.lastname: Morabito
authors.forename: M
authors.initials: M
authors.lastname: Brugiatelli
authors.forename: B
authors.initials: B
authors.lastname: Jaksic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000401:mortality / Q000473:pathology*; D017254:Leukemic Infiltration / Q000175:diagnosis / Q000401:mortality / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015999:Multivariate Analysis; D011379:Prognosis; D012737:Sex Factors; D016019:Survival Analysis; D016896:Treatment Outcome