PMID- 17541398
OWN - NLM
STAT- MEDLINE
DCOM- 20070925
LR  - 20220419
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 21
IP  - 8
DP  - 2007 Aug
TI  - Chromosomal translocations independently predict treatment failure, 
      treatment-free survival and overall survival in B-cell chronic lymphocytic 
      leukemia patients treated with cladribine.
PG  - 1715-22
AB  - Chromosomal translocations represent an important prognostic indicator in B-cell 
      chronic lymphocytic leukemia (B-CLL). However, their value had been neither 
      determined in homogeneously treated patients nor compared to that of IgV(H) 
      mutational status. Sixty-five B-CLL patients were investigated using 
      cytogenetics, interphase fluorescence in situ hybridization (FISH), analysis of 
      IgV(H) and of TP53 mutational status before treatment with 
      2-chloro-2'-deoxyadenosine (CdA). Translocations (n=45) were detected in 42% of 
      the patients, including both balanced (n=12) and unbalanced (n=33) types. IgV(H) 
      was mutated in 43% of the patients. Patients with translocations were more 
      heavily pretreated (P=0.05), presented with more complex karyotypes (P<0.001), 
      17p abnormalities and TP53 mutations, and had a higher failure rate (59 vs 21% in 
      patients without translocations, P=0.004). Patients with unbalanced 
      translocations displayed a shorter median treatment-free survival (TFS, 6.9 vs 
      35.9 months, log rank 22.72, P<0.001) and overall survival (OS, 13.0 vs 68.0 
      months, log rank 16.51, P<0.001), as compared to patients without translocation. 
      In multivariate analysis, unbalanced translocations were independently associated 
      with therapeutic failure, short TFS and short OS. IgV(H) mutational status was 
      independently associated with risk of failure and TFS, but not OS. In B-CLL 
      patients treated with CdA, translocations are strong predictors of outcome.
FAU - Van Den Neste, E
AU  - Van Den Neste E
AD  - Department of Hematology/Hematological Biology, Cliniques Universitaires UCL 
      Saint-Luc, Brussels, Belgium. vandenneste@sang.ucl.ac.be
FAU - Robin, V
AU  - Robin V
FAU - Francart, J
AU  - Francart J
FAU - Hagemeijer, A
AU  - Hagemeijer A
FAU - Stul, M
AU  - Stul M
FAU - Vandenberghe, P
AU  - Vandenberghe P
FAU - Delannoy, A
AU  - Delannoy A
FAU - Sonet, A
AU  - Sonet A
FAU - Deneys, V
AU  - Deneys V
FAU - Costantini, S
AU  - Costantini S
FAU - Ferrant, A
AU  - Ferrant A
FAU - Robert, A
AU  - Robert A
FAU - Michaux, L
AU  - Michaux L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070531
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 47M74X9YT5 (Cladribine)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*therapeutic use
MH  - Chromosome Aberrations
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Chromosomes, Human, Pair 13/genetics
MH  - Chromosomes, Human, Pair 17/genetics
MH  - Cladribine/*therapeutic use
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Interphase
MH  - Karyotyping
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/*genetics/*mortality
MH  - Male
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Prognosis
MH  - Risk Factors
MH  - Survival Rate
MH  - *Translocation, Genetic
MH  - Treatment Failure
MH  - Tumor Suppressor Protein p53/genetics/metabolism
EDAT- 2007/06/02 09:00
MHDA- 2007/09/26 09:00
CRDT- 2007/06/02 09:00
PHST- 2007/06/02 09:00 [pubmed]
PHST- 2007/09/26 09:00 [medline]
PHST- 2007/06/02 09:00 [entrez]
AID - 2404764 [pii]
AID - 10.1038/sj.leu.2404764 [doi]
PST - ppublish
SO  - Leukemia. 2007 Aug;21(8):1715-22. doi: 10.1038/sj.leu.2404764. Epub 2007 May 31.