Multivariable model consisting of clinical and biological markers for time to first treatment in CLL patients: Preliminary results from single centre experience.

INTRODUCTION: 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. MATERIAL AND 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, ß-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. CONCLUSION: 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.

Diagnostic value of brush border enzymes of the proximal renal tubules in rheumatoid arthritis.

BACKGROUND: Proximal tubules of the kidney have a dominant function in the excretion of different enzymes in the urine. These enzymes can be used as markers for secondary renal damage under the action of different diseases, medicines, and toxins. The aim of this study was to evaluate the values of alanine aminopeptidase (AAP), gamma-glutamyl transferase (gamma-GT), and beta2 microglobulin (beta2m) in urine of patients with untreated rheumatoid arthritis (RA) and to define the possible association between untreated rheumatoid arthritis and tubular function at the brush border region. METHODS: We used a kinetic assay for AAP, standard methods by the International Federation for Clinical Chemistry (IFCC) for gamma-GT and Microparticle Enzyme Immunoassay (MEIA), (Abbott A(x)SYM System) for the determination of beta2m in urine of 70 participants (35 untreated RA patients and 35 healthy volunteers (HC)). RESULTS: From the total of 35 RA patients, AAP enzymuria was found in 24 patients with test sensitivity (68.57%), gamma-GT in 16 patients with test sensitivity (45.71%), while the presence of urinary beta2m was found in a very low percentage of cases. Out of 18 rheumatoid factor (RF) negative patients, 14 patients were AAP and 10 patients were gamma-GT positive, while the presence of beta2m in urine was not detected. Among 17 RF positive RA patients, the presence of AAP and gamma-GT was noticed in 10 and 6 patients, respectively, while the presence of beta2m in urine was not detected. CONCLUSIONS: In conclusion, AAP had a higher sensitivity than gamma-GT and beta2m in detection of asymptomatic renal lesions in untreated RA.