Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first-line chronic lymphocytic leukemia.
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disorder of remarkable heterogeneity as demonstrated by cytogenetics and molecular analyses. Complex karyotype (CK), TP53 deletions and/or mutations (TP53 disruption), IGVH mutational status, and, more recently, recurrent somatic mutations have been identified as prognostic markers in CLL. On a cohort of 110 patients with CLL treated with first-line fludarabin, cyclophosphamide, and rituximab treatment compared with 33 untreated (watch and wait) patients with CLL, we report more frequent complex karyotypes (34 vs 15%; P = .05), unmutated IGHV (70 vs 21%; P < .0001), ATM deletion (25 vs 6%, P = .02), and NOTCH mutation (3 vs 17%, P = .04). Among treated patients, 39 relapsed during the follow-up period. These patients were characterized before treatment by a higher incidence of trisomy 12 (38 vs 11%, P < .001) and TP53 disruption (31 vs 4%, P = .0002). A significantly shorter 5-year overall survival was found for treated patients with CK (72.4 vs 85.8%; P = .007), unmutated IGHV (70 vs 100%; P = .04), or TP53 disruption (55.7 vs 82.7%; P < .0001). Three risk groups were defined based on the status of TP53 disruption or unmutated IGVH, which differed significantly in terms of 5-year overall survival. Moreover, the presence of CK impacted pejoratively 5-year overall survival and progression-free survival in all these 3 groups. Conventional karyotyping therefore appears to be of value, CK being an additional factor, undetectable in classical FISH, in patients with CLL at the stage when therapy becomes required.
Laboratoire d'Hématologie, CHU de Toulouse, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.|Service d'Hématologie Biologique, CHU de Nantes, Nantes, France.
Yannick
Y
Le Bris
Laboratoire d'Hématologie, CHU de Toulouse, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.
Stéphanie
S
Struski
Service d'Hématologie Clinique, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
Romain
R
Guièze
Laboratoire d'Hématologie, CHU de Toulouse, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.
Caroline
C
Rouvellat
Laboratoire d'Hématologie, CHU de Toulouse, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.
Naïs
N
Prade
Laboratoire d'Hématologie, CHU de Caen, Caen, France.
Xavier
X
Troussard
Service d'Hématologie Clinique, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
Olivier
O
Tournilhac
Service d'Hématologie Biologique, CHU de Nantes, Nantes, France.
Marie C
MC
Béné
Laboratoire d'Hématologie, CHU de Toulouse, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.
Eric
E
Delabesse
Service d'Hématologie Clinique, CHU de Toulouse, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France.
Loïc
L
Ysebaert
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D059785:Karyotype; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality*; D008297:Male; D009154:Mutation; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D016159:Tumor Suppressor Protein p53
CLL; IGHV; TP53; complex karyotype