Haematologica 2003 - Supplements

Objective: To compare the impact on disease outcome of
abnormalities on chromosome 13 detected by FISH vs karyotype
detection in a series of MM patients treated with intensive
chemotherapy.
Material and Methods: Cytogenetics (CG) and FISH analysis
(LSI 13/RB1 probe, Vysis Inc.) were performed simultaneously
in 318 consecutive patients with newly diagnosed MM, registered
in the Spanish GEM trial since January 2000. So far, a
preliminary prognosis study have been carried out in the first 140
enrolled patients which had clinical, biological and follow-up
data available.
Results: An abnormal karyotype was detected in 48/120 (40%)
successful cultures, of whom 13 (11%) showed chromosome 13
monosomy. A del(13q) by FISH was present in 35 of the 140
patients (25%): all patients with -13 by CG had del(13q) by FISH
(group 1: CG+/FISH+) and in addition, FISH detected del(13q) in
16/92 (17%) patients with normal or non informative karyotype
(group 2: CG-/FISH+). 13q- by FISH was significantly associated
with hypodiploidy (12 patients, p=0.005), and high serum
2microglobulin (p=0.007), calcium (p=0.02) and % of bone
marrow plasma cells (p=0.009). Patients with 13q- detected either
by CG or FISH showed very poor prognosis. Upon comparing the
outcome of group 1 vs group 2 patients no significant differences
were observed. The estimated median EFS times were 17.4 vs
93.7 months for patients with and without del(13q), respectively.
Abnormal karyotype affected EFS but not OS and the median
EFS time (23.2 months) was longer than that observed in del
(13q) group (17.4 months). When impact of del(13q) was
analysed in the normal karyotype group, the adverse outcome of
this abnormality remained invariable. On multivariate analysis,
the most important negative factor for both EFS and OS was
del(13q) (p35%. 74% of the
patients were in stage III. All patients were homogeneously
treated according to Spanish protocols (PETHEMA 94 and 96).
Survival analysis was carried out on the group of 73 patients
treated with conventional chemotherapy without autotransplant.
Methods: Comparative genomic hybridization was carried out in
all patients. Ratio values above 1.25 and below 0.75 were
considered to represent chromosomal gains and losses
respectively. A high-level amplification was considered when the
fluorescence ratio values exceeded 1.5. Abnormalities on
chromosomes 13 and 11 were confirmed by FISH. In all cases the
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