title: Multivariable model consisting of clinical and biological markers for time to first treatment in CLL patients: Preliminary results from single centre experience.
abstract: BACKGROUND
  The clinical course for patients with chronic lymphocytic leukaemia (CLL) is extremely heterogeneous; one of the most important challenges in the clinical management of these patients is the decision on initiating their treatment, but there is no available prognostic system that will resolve this issue. Usually, criteria for active disease are used to initiate therapy. Recently, some authors have proposed prognostic models, scoring systems involving a set of clinical and biological risk factors and estimates of individual patient survivals. Here, we report our initial results from a study designed to evaluate the statistical association of the distinct clinical and biological parameters with the prognosis and time to initiating treatment for patients with CLL.
  
  
  METHODS
  Our study incorporated 100 consecutive, treatment naive CLL patients. In each patient all traditional laboratory, clinical and biological prognostic factors were evaluated at their first visit to our Institution. We then combined the following independent characteristics: age, β-2 microglobulin, absolute lymphocyte count, sex, Rai stage, and number of involved lymph node groups, which are included in some of the already published CLL prognostics index, in association with the CD38 expression and mutational status of the immunoglobulin heavy chain gene variable region (IGVH). Further, we correlated those factors by multivariable analysis with time to first treatment. This multivariable model was used to develop a nomogram-a weighted tool to calculate 5- and 10-year survival probability and estimate median time to first treatment (TFT).
  
  
  RESULTS
  According to the prognostic index, a classification tree was built that identified three subsets of patients whose scores were 1-3 (low risk - 32 pts - 32%), 4-7 (intermediate risk - 48 pts - 48%) and > 8 (high risk - 20 pts - 20%). Estimated median survival in the low risk subset of patients is 141 years, and 10.7 and 4.6 years respectively in the intermediate and high risk subsets of patients. Projected survival in respectively low, intermediate and high-risk groups are 100%, 100%, 25%, and 43%, 34%, 25% at 5 years and 10 years, respectively. Also, statistical analyses showed that among other things CD38 expression and unmutated IGHV mutation status are associated with a shorter time to first treatment.
  
  
  CONCLUSIONS
  Our prognostic model that combines and correlates the distinct clinical and biological markers of CLL patients enables identification of patients who are at high risk of progression. This prognostic model may facilitate the clinical decision for initiating treatment.
authors.affiliation: University Haematology Clinic, Medical Faculty, Ss. Cyril and Methodius University, Skopje, R. Macedonia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Trajkova
authors.forename: Lidija
authors.initials: L
authors.lastname: Cevreska
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Pivkova-Veljanovska
authors.forename: Martin
authors.initials: M
authors.lastname: Ivanovski
authors.forename: Dusko
authors.initials: D
authors.lastname: Dukovski
authors.forename: Marija
authors.initials: M
authors.lastname: Popova-Simjanovska
authors.forename: Lazar
authors.initials: L
authors.lastname: Cadievski
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Eftimov
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Dimovski
authors.forename: Irina
authors.initials: I
authors.lastname: Panovska-Stavridis
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor