Assessment of red blood cell distribution width as a prognostic marker in chronic lymphocytic leukemia

Abstract

Red blood cell distribution width (RDW) is a quantitative measure of the variability in size of circulating erythrocytes. It was recently reported that RDW is a prognostic factor for infection diseases, cardiovascular and pulmonary diseases, as well as some neoplasms. Moreover, RDW is remarkably strong predictor of longevity, including all causes of death, for adults aged 45 years and older. To explain this occurrence it was proposed that persistent IGFs/mTOR signaling is one of the factors that play a role in affecting the RDW and mortality.The above observations induced us to analyze the prognostic role of RDW in chronic lymphocytic leukemia (CLL) being the most frequent type of adult leukemia in Western countries. The obtained results have shown that RDW may be considered as a potential CLL prognostic marker. Elevated RDW level at the moment of diagnosis was associated with advanced disease and presence of other poor prognostic factors. It is also connected with overall survival indicating shorter time in patients with elevated RDW. It is possible that the presently observed correlation between mortality and RDW of the CLL patients is affected by their metabolic (IGF-1/mTOR driven)- rather than chronological- aging. The patients with high level of RDW are expected to have an increased persistent level of IGF-1/mTOR signaling. Within the framework of personalized therapy, these CLL patients therefore would be expected to be more sensitive to the treatment with mTOR inhibitors.

Keywords: CD38; CLL; RDW; ZAP-70; mTOR.

Figure 1. Clinical stadium according to Rai classification [30] of the analyzed CLL patients in High-RDW group (RDW > 14.5%) and Low-RDW group (RDW < 14.5%)

Figure 2. RDW values in CLL risk groups

RDW values in ZAP-70 negative (ZAP-70-) and ZAP-70 positive (ZAP–70+) CLL patients (A). RDW values of CLL patients in CD38 negative (CD38−) and CD38 positive (CD38+) group (B). RDW values of analyzed patients in the standard-risk cytogenetic group (del13q14.3, trisomy 12, or no changes detected) and in the high-risk cytogenetic group (17p13.1 or 11q22.3) (C). All graphs show mean ± standard deviation. NS not statistically significant.

Figure 3. Time to treatment (A) and total survival time (B) demonstrated by Kaplan-Meier curves

The patients were stratified according to RDW level (Low-RDW group versus High-RDW group). Statistical significance is indicated.