Prospective validation of a risk score based on biological markers for predicting progression free survival in Binet stage A chronic lymphocytic leukemia patients: results of the multicenter O-CLL1-GISL study.
A risk score based on three biological features (CD38, ZAP-70, and IGHV mutational status) was previously developed to predict progression-free survival (PFS) in untreated Binet A CLL patients. Here we perform a score validation analysis in a prospective and independent cohort of patients. Biological markers (CD38, ZAP-70, and IGHV mutational status) and gene expression profiles (GEP) of leukemic cells from CLL patients included in a prospective multicenter observational study (O-CLL1-GISL protocol, clinicaltrial.gov ID:NCT00917549) were used to assess the value and reproducibility of this score. To date, 468 Binet A patients were classified as low- (0 positive marker), intermediate- (1 positive marker), or high-risk (2 or 3 positive markers) using the progression risk score. The 3-year PFS probability was 91.7%, 82.9%, and 57.4% for low-, intermediate-, and high-risk (P < 0.0001) cases, respectively. These values were similar to those found in the original cohort. At Cox multivariate analysis, Rai stage, absolute lymphocyte count, progression risk score, and β-2 microglobulin maintained an independent prognostic impact on PFS. This score remained a predictor of progression when analysis was limited to 371 Rai 0 cases (P < 0.0001). Finally, the cells from the different CLL risk groups showed differences in their gene expression patterns. These results confirm the ability of this progression risk score to predict PFS among Binet A patients. The utility of the score was also extended by demonstrating that it retains prognostic value when applied exclusively to Rai 0 patients. Specific transcriptional patterns were significantly associated with risk groups.
Hematology Unit, Department of Onco-hematology, A.O. of Cosenza, Cosenza, Italy.
Massimo
M
Gentile
Giovanna
G
Cutrona
Laura
L
Mosca
Serena
S
Matis
Sonia
S
Fabris
Marta
M
Lionetti
Fiorella
F
Ilariucci
Simona
S
Zupo
Caterina
C
Musolino
Luciano
L
Levato
Stefano
S
Molica
Francesco
F
Di Raimondo
Iolanda
I
Vincelli
Nicola
N
Di Rienzo
Emanuela Anna
EA
Pesce
Francesco
F
Angrilli
Massimo
M
Federico
Antonino
A
Neri
Manlio
M
Ferrarini
Fortunato
F
Morabito
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment
D014408:Biomarkers, Tumor
biological markers; chronic lymphocytic leukemia; early stage; gene expression profiles; prognosis