MD Anderson Cancer Center (MDACC) Score Adds Prognostic Information To The Distinction Between High COUNT Monoclonal B-CELL Lymphocytosis (HC-MBL) and RAI STAGE 0 Chronic Lymphocytic Leukemia (CLL)

Immunogenetic characteristics and clinical outcome findings suggest that high-count monoclonal B-cell lymphocytosis (HC-MBL) (i. e, more than 0.5 x 10E9 clonal B cells/L in peripheral blood) and Rai stage 0 CLL (i. e, more than 5.0 x 10E9 clonal B cells/L in peripheral blood) are similar entities. However, it is not clear whether prognostic variables generally useful to forecast the likelihood of transformation to an active phase of disease requiring therapy of patients with early CLL can be applied to subjects with HC-MBL. We therefore analyzed clinical outcome of a multi-institutional, prospective cohort including 94 subjects with HC CLL-like (i.e., CD19-, CD5-, CD23-positivity, and CD20dim expression) MBL and 158 Rai stage 0 CLL patients diagnosed at different Italian hematologic institution between January 2006 and December 2010 (O-CLL1 protocol; clini- caltrial.gov identifier NCT00917540). In this cohort we wondered whether the new prognostic index proposed by MD Anderson Cancer Center (MDACC) which includes either clinical (i.e., number of lymph node sites involved, lymph node size in neck, LDH) or biological (i.e., mutational status of IGHV, presence of 11q or 17p deletion by FISH) variables could add prognostic information to that afforded by distinction between HC-MBL and Rai stage 0.

Using time to first treatment (TTFT) as endpoint, we found that likelihood to receive therapy was significantly lower for subject with HC-MBL in comparison to patients in Rai stage 0 (P<0.001). Furthermore, a total point score of 25, used as threshold, identified two different patterns of TTFT among either subjects with HC-MBL (P=0.02) or patients with Rai stage 0 CLL (P<0.001). We then stratified our cohort taking into account either the distinction between HC-MBL and Rai stage 0 or MDACC prognostic index. Accordingly, 4 groups were identified: 1. HC-MBL with MDACC total point score lower than 25 (n=66); 2. HC-MBL with MDACC total point score equal or higher than 25(n=28); 3. Rai stage 0 with MDACC total point score lower than 25 (n=74); 4. Rai stage 0 with MDACC total point score equal or higher than 25 (n=84). The probability of remaining free from therapy at 5 years was 97% for subjects with HC-MBL and MDACC score lower than 25 while it was 20% for patients with Rai stage 0 and score equal or higher than 25. In between there were HC-MBL subjects with MDACC total point scorre equal or higher than 25 and Rai stage 0 patients with MDACC total point score lower than 25. Curves of TTFT of these two groups virtually overlapped and 5-year probability of remaining free from therapy was 68% for both.

In conclusion, we demonstrated that MDACC score adds information to the distinction between HC-MLB and Rai stage 0 leading to the identification of three significantly different patterns of TTFT on the basis of objective data of clinical outcome (P<0.0001) (Fig1). These results support the idea that HC-MBL and Rai stage 0 are a mixture of real patients whose clinical outcome is affected by the disease but also of individuals who will never develop clinical signs and symptoms.

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