The chronic lymphocytic leukemia international prognostic index predicts time to first treatment in early CLL: Independent validation in a prospective cohort of early stage patients

Abstract

The chronic lymphocytic leukemia International Prognostic Index (CLL-IPI) combines 5 parameters (age, clinical stage, TP53 status [normal vs. del(17p) and/or TP53 mutation], IGHV mutational status, serum β2-microglobulin) to predict survival and time-to-first-treatment (TTFT) in CLL patients. We performed an observational study in 337 prospectively collected, Binet stage A patients to validate the ability of the CLL-IPI to predict TTFT in an independent cohort of early stage CLL patients. The CLL-IPI score stratified Binet stage A patients into three subgroups with different outcome. Since the CLL-IPI was originally developed to predict survival, we next investigated the optimal cut-off score to predict TTFT in Binet stage A patients. Recursive partitioning analysis identified three subsets with scores of 0 (n = 139), 1 (n = 90), and ≥ 2(n = 108). The probability of remaining free from therapy 5 years after diagnosis was 85%, 67% and 46% in these three categories (P < 0.0001.; C-statistic:c = 0.72; 95% CI:0.58-0.81). This optimized CLL-IPI scoring for TTFT was subsequently validated in an independent cohort of Binet A patients from the Mayo Clinic (n = 525). The ability of either original or optimized CLL-IPI to predict TTFT was equivalent to other prognostic models specifically designed for this endpoint (2011 MDACC score and O-CLL1 score). Although originally developed to predict suvival, the CLL-IPI is useful for predicting TTFT in early stage CLL patients. Am. J. Hematol. 91:1090-1095, 2016. © 2016 Wiley Periodicals, Inc.

Keywords: leukemia.

Figure 1

(A) Kaplan-Meier estimate of time to first treatment (TTFT) of Binet stage A patients stratified according to CLL-IPI score: Low-risk (CLL-IPI score 0–1); Intermediate-risk (CLL-IPI score 2–3); High-risk (CLL-IPI score ≥ 4). (B) TTFT of Binet A CLL patients based on Revised Scoring System Derived from Recursive Partitioning (RPART). The CLL-IPI risk categories were the following: Low-risk (CLL-IPI score 0); Intermediate-risk (CLL-IPI score 1); High-risk (CLL-IPI score ≥ 2).

Figure 2

(A)) TTFT of Rai stage 0 patients based on revised scoring system derived from Recursive Partitioning (RPART). The CLL-IPI risk categories were the following: Low-risk (CLL-IPI score 0); Intermediate-risk (CLL-IPI score 1); High-risk (CLL-IPI score ≥ 2). (B) TTFT of Rai stage 0 patients based on the original CLL-IPI: Low-risk (CLL-IPI score 0–1); Intermediate-risk (CLL-IPI score 2–3); High-risk (CLL-IPI score ≥ 4).

Figure 3

(A) TTFT of Rai stage 0-II patients (Mayo clinic cohort) based on the original CLL-IPI: Low-risk (CLL-IPI score 0–1); Intermediate-risk (CLL-IPI score 2–3); High-risk (CLL-IPI score ≥ 4). (B) TTFT of Rai stage 0-II patients (Mayo clinic cohort) based on the revised CLL-IPI: The CLL-IPI risk categories were the following: Low-risk (CLL-IPI score 0); Intermediate-risk (CLL-IPI score 1); High-risk (CLL-IPI score ≥ 2).