A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia

Abstract

W e present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia (CLL) developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count >32.0x10 3 /microliter, 1 point. Low-, intermediate-and high-risk categories were established by recursive partitioning in a training cohort of 478 cases, and then validated in four independent cohorts of 144 / 395 / 540 / 322 cases, as well as in the composite validation cohort. Concordance indices were 0.75 in the training cohort and ranged from 0.63 to 0.74 in the four validation cohorts (0.69 in the composite validation cohort). These findings advocate potential application of our novel prognostic calculator to better stratify early-stage CLL, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 CLL being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemofree era.

CLL-IPI applied in Binet A CLL: a nationwide cohort study

“…1,[12][13][14][15][16][17][18] The recently developed laboratory-based prognostic calculator demonstrated superior or equal discriminatory power compared with CLL-IPI for TFS across validation cohorts (0.63-0.72 vs. 0.61-0.70), with most estimates within the CI of TTFT in our study. 11 The international prognostic score-A, a novel score including genetic and clinical variables for predicting TTFT in early stage CLL, has exhibited c-statistics (0.66-0.75) similar to CLL-IPI in direct comparison and with estimates within our CI. 9,18 Studies applying the observational-CLL1 score for TTFT or TFS, which uses genetic and clinical variables, have also found c-statistics (0.69-0.75) comparable to ours, and with identical estimates or overlapping CIs when comparing directly to CLL-IPI.…”

“…However, it was similar to previous findings for TTFT and treatment-free survival (TFS) in newly diagnosed Binet stage A (0.69-0.70) and Rai stage 0 (0.61-0.75) and OS in Rai stage 0 (0.65), with most estimates overlapping our CIs. 4,[9][10][11] Several approaches have been developed for assessing the prognosis of newly diagnosed patients with CLL, though the performance of the predictions has not improved over time. 1,[12][13][14][15][16][17][18] The recently developed laboratory-based prognostic calculator demonstrated superior or equal discriminatory power compared with CLL-IPI for TFS across validation cohorts (0.63-0.72 vs. 0.61-0.70), with most estimates within the CI of TTFT in our study.…”

Precision Medicine Management of Chronic Lymphocytic Leukemia

“…Recent studies have tried to identify the clinical and molecular features of early stage CLL patients managed with a watch and wait approach and who might manifest treatment requirement soon after diagnosis [6,[55][56][57][58]. The pattern of tumor growth of untreated CLL has been investigated by analyzing serial longitudinal samples collected between diagnosis and the time of treatment requirement [6].…”

Lymphocyte Doubling Time As A Key Prognostic Factor To Predict Time To First Treatment In Early-Stage Chronic Lymphocytic Leukemia

“…The breakthrough of novel biologic variables has led to several prognostic indexes to weigh TTFT in early-stage (Binet A) CLL patients (1,2,(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52). Indeed, over the past few years, there has been a great effort to use novel molecular markers in prognostic modeling.…”