An international consortium devised an international prognostic index for chronic lymphocytic leukemia (CLL-IPI) that combines genetic, biochemical, and clinical parameters into a prognostic model to enable more targeted management of patients with CLL.1

Novel therapies and an array of biologic and genetic variables that enhance clinical staging systems for CLL are improving disease management for patients with CLL. These researchers sought to create an index that integrates the major prognostic parameters to allow for more targeted management of patients with the disease.

For the study, the researchers used a systematic search of the Cochrane Haematological Malignancies Group of MEDLINE, Embase, and Central databases. Their search identified 13 prospective, clinical phase 2 and 3 trials of CLL, published between January 1, 1950, and December 31, 2010. Of these 13 trials, the principal investigators of 8 phase 3 trials from France, Germany, Poland, the United Kingdom, and the United States agreed to provide individual patient data. These data were used to create the full analysis dataset (N = 3472 treatment-naïve patients).

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Overall survival was determined by univariate analysis and multivariate analyses using 27 baseline factors. Discriminatory value was assessed using C-statistics; subgroup analysis was used to assess the validity and reproducibility of the CLL-IPI. In addition, datasets from the Mayo Clinic (Rochester, Minnesota; MAYO cohort [N = 838 patients]) and the SCALE Scandinavian population-based case-control study (SCAN cohort [N = 416]) were used as external-validation datasets.

Using a random sample procedure, the full analysis dataset was randomly divided into a training dataset (N = 2308 patients) and an internal-validation dataset (N = 1164 patients). Independent prognostic factors identified in the training dataset included:

  • TP53 status (no abnormalities vs del[17p] or TP53 mutation or both)
  • IGHV mutational status (mutated vs unmutated)
  • Serum β2-microglobulin concentration (up to 3.5 mg/L vs more than 3.5 mg/L)
  • Clinical stage (Binet A or Rai 0 vs Binet B–C or Rai I–IV)
  • Age (65 years and younger vs older than 65 years).

Using a weighted risk score assigned to each independent factor, a prognostic index of 4 risk groups with significantly different overall survival at 5 years were identified within the training dataset: low risk (93.2% [95% CI, 90.5–96.0]), intermediate risk (79.3% [95% CI, 75.5–83.2]), high risk (63.3% [57.9–68.8]), and very high risk (23.3% [12.5–34.1]; log-rank test comparing survival across the 4 risk groups P < .0001; C-statistic, c = 0.723 [95% CI, 0.684–0.752]). These risk groups were confirmed in both validation datasets.

“The index will allow a more targeted management of patients with CLL in clinical practice and in trials testing novel drugs,” reported the researchers.

This study received funding from José Carreras Leukaemia Foundation.


1. International CLL-IPI Working Group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data [published online May 13, 2016]. Lancet Oncol. doi:10.1016/S1470-2045(16)30029-8.