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Major prognostic value of complex karyotype in addition to TP53 and IGHV mutational status in first‐line chronic lymphocytic leukemia
Author(s) -
Le Bris Yannick,
Struski Stéphanie,
Guièze Romain,
Rouvellat Caroline,
Prade Naïs,
Troussard Xavier,
Tournilhac Olivier,
Béné Marie C.,
Delabesse Eric,
Ysebaert Loïc
Publication year - 2017
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.2349
Subject(s) - ighv@ , chronic lymphocytic leukemia , karyotype , trisomy , medicine , fludarabine , oncology , cyclophosphamide , cytogenetics , gastroenterology , immunology , leukemia , biology , chemotherapy , genetics , chromosome , gene
Abstract 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.