Predictive value of the CLL-IPI in CLL patients receiving chemo-immunotherapy as first-line treatment

An international collaboration has led to the development of a comprehensive tool [CLL-IPI international prognostic index for CLL] for the predicting of overall survival (OS) in chronic lymphocytic leukemia (CLL).1 CLL-IPI was based on data collected from 3500 CLL patients and was based on the following parameters: TP53 deletion and/or mutation, IGHV mutational status, \u3b22-microglobulin plasma levels, clinical stage, and age. CLL-IPI provides the means to stratify CLL patients in the daily clinical practice (Supplementary Table 1).1 Although validated for OS2-4 and time to first treatment (TTFT),5 the predictive value of CLL-IPI on progression-free survival (PFS) has until now only been demonstrated in a single study on patients treated with chlorambucil (CLB), as monotherapy, or in combination with obinutuzumab or rituximab, as a first-line approach (CLL11 study),6 and presented as a poster at the annual meeting of the American Society of Hematology (ASH) in 2016

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture

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

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 \u3b22-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\u2009 65\u20092(n = 108). The probability of remaining free from therapy 5 years after diagnosis was 85%, 67% and 46% in these three categories (P\u2009<\u20090.0001.; C-statistic:c\u2009=\u20090.72; 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