PB1902 THE BARCELONA‐BRNO BIOMARKERS‐ONLY PROGNOSTIC MODEL FOR CHRONIC LYMPHOCYTIC LEUKEMIA ‐ SINGLE CENTRE EXPERIENCE
Authors: Tomic K. , Vukovic V. , Antic D. , Bukumiric Z. , Karan‐Djurasevic T. , Dencic‐Fekete M. , Djurasinovic V. , Otasevic V. , Knezevic V. , Tosic N. , Pavlovic S. , Mihaljevic B. 
Published: June 2019

Background:

The Barcelona‐Brno biomarkers‐only chronic lymphocytic leukemia (CLL) prognostic model is a new, simplified version of the International Prognostic Index for Chronic Lymphocytic Leukemia (CLL –IPI), developed for outcome prediction on the basis of the two most important prognostic markers in CLL, mutational status of immunoglobulin heavy variable (IGHV) genes and cytogenetic abnormalities detected by fluorescent in situ hybridization (FISH).

Aims:

The aim of this study was to evaluate the prognostic power of the biomarkers‐only CLL prognostic model in a cohort of Serbian CLL patients.

Methods:

This retrospective study enrolled a total of 133 unselected CLL patients, which were diagnosed, managed and followed in Clinic of Hematology, Clinical Center of Serbia, Belgrade, Serbia. All patient data (clinical and laboratory parameters at diagnosis, FISH cytogenetics performed prior to first therapy and IGHV mutational status) were collected from patients’ medical records and patients were stratified according to the biomarkers‐only CLL prognostic model. Comparison of overall survival (OS) and time to first treatment (TTFT) between risk groups was conducted using the Kaplan‐Meier method and log‐rank test.

Results:

The median age at diagnosis was 59 years (range 30–88). Male to female ratio was 1.96. Forty‐four percent of patients were diagnosed with Binet stage A, 38% with Binet B, and 18% with Binet C. Regarding IGHV mutational status, 59 patients (44.4%) were mutated, and 74 patients (55.6%) were unmutated. Normal karyotype, del(13q), del(11q), trisomy(12), and del(17p) were detected by FISH in 48.1%, 29.3%, 10.5%, 7.5%, and 4.5% of patients, respectively. According to the biomarkers‐only prognostic model, 54 patients (40.6%) were assigned as low risk, 65 (48.9%) as intermediate risk and 14 (10.5%) as high risk. During the median follow‐up of 9 years, 42.9% of patients died and 81.2% received treatment. Patients were treated in the first line as follows: 80 (74%) with fludarabine‐based therapy (61% FC, 39% FCR), 8 (7%) with cyclophosphamide, vincristine and prednisone (COP), 15 (16%) with chlorambucil, and 3 patients (3%) with other treatment options.

The median TTFT in our cohort was 55 months (95%CI 0–125 months). Patients in low risk group had significantly longer median TTFT (168 months) in comparison to patients in intermediate (29 months) and high (38 months) risk groups (Log rank test across groups p < 0.001)(Figure 1A). However, the difference in median TTFT between the latter two risk groups was not significant. In our cohort median OS was 108 months (95%CI 78‐138 months). Similarly to TTFT, median OS in low risk group was significantly longer (not reached) in comparison to median OS in intermediate and high‐risk groups (82 and 94 months, respectively)(Log rank test across groups p < 0.001)(Figure 1B). Again, no significant difference in OS between intermediate and high risk groups was observed.

The biomarkers‐only model was also shown to be a good predictor of TTFT and OS in patients younger than 65 years (p < 0,001), but not in older patients (≥65 years). In addition, the model successfully stratified patients within Binet A and B group regarding both TTFT (p = 0.003 and p = 0.007, respectively) and OS (p = 0.018 and p = 0.009, respectively), while it was not relevant in the Binet C group.

Summary/Conclusion:

The Barcelona‐Brno biomarkers‐only CLL prognostic model is an effective prognostic marker in Serbian CLL patients regarding both TTFT and OS, especially in younger patients and Binet A or B patients with low risk disease.

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