12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
used to assess the two common polymorphisms in the MTHFR gene.
Results. MTHFR 677T genotype frequencies in CML and controls were
25.29% and 13.76%, respectively. MTHFR 1298C genotype frequencies
in CML and controls were 11.76% and 7.84%, respectively. The
MTHFR 677T genotype frequency in CML patients was significantly different
from controls [p=0.03]. MTHFR 1298C genotype frequency was
only marginally lower in cases compared to controls [p =0.05]. Conclusions.
On the basis of the present results it is suggested that decreased
MTHFR activity associated with the presence of the 677T genotype,
may result in increased stability of DNA leading to a protective effect
against CML. Also the effect of the 1298C genotype, even less prominent,
on DNA stability cannot be excluded. Understanding genetic susceptibility
to CML, with particular respect to folate metabolism, will
allow the identification of novel therapeutic strategies. Further studies
are ongoing in a larger population of CML patients, also in relation to
potential susceptibility to ABL kinase domain mutations development
and subsequent resistance to therapy with tyrosine kinase inhibitors.
Results will be presented.
Supported by: European LeukemiaNet, COFIN 2003 (M. Baccarani), Ateneo
Grant (GM), AIL, AIRC, Fondazione Del Monte di Bologna e Ravenna.
0537
IMPACT OF CYTOGENETIC ABERRATIONS IN PHILADELPHIA CHROMOSOME NEGATIVE
HEMATOPOIESIS ON EVENT-FREE SURVIVAL OF CHRONIC MYELOID LEUKEMIA
PATIENTS TREATED WITH IMATINIB MESYLATE
F. Maloisel, 1 S. Struski, 2 C. Gervais, 2 A. Zamfir, 3 A.C. Voegeli, 4
B. Lioure, 3 M.P. Gaub4 1 Hôpitaux Universitaires, STRASBOURG; 2 Laboratory Hematology blood coagulatio,
STRASBOURG; 3 Department of Hematology & Oncology, STRAS-
BOURG; 4 Laboratory of Molecular Biology, STRASBOURG, France
Background. Clonal aberrations (CA) of Philadelphia (Ph) negative
metaphases have been described after treatment with interferon α or
imatinib (IM) in a minority of patients (pts) with cytogenetic response.
Conflicting data suggest selection of pre-existing clones versus induction
of aneuploidy by tyrosine kinase inhibitors. The prognostic impact of
aberrations in the Ph negative hematopoiesis for the individual pts
remains to be determined. Aims. To evaluate the incidence and prognostic
impact of CA occurring during imatinib therapy, we retrospectively
analysed the outcome of our pts with chronic (CP) or accelerated phase
(AP) of CML who obtained at least a major cytogenetic response during
the first year of IM treatment. Material and Methods. between april 2000
and December 2006, 127 pts received IM and 90 obtained a partial cytogenetic
response (PCR) or complete cytogenetic response (CCR) during
the first year of treatment. Cytogenetic analysis was performed every 3
months during the first year and every 6 months after. CA was defined
as abnormalities seen in 2 or more metaphases. Two groups were
defined according with the presence or not of CA. Characteristics of
each population (age, sex, prior therapies, sokal index, disease phase,
response, bcr-abl kinetic) were analysed. During the follow-up, relapse,
progression of the disease or death was noted. Results. with a median
time of follow-up of 41 months, 32 pts developed CA (35%). The median
time from the start of IM to appearance of CA was 278 days (range
82-1495 d). In 15 pts these events have been transient and disappeared
after a median of 4 months (range, 3-9 months). CA were: -7/del 7 (6 pts);
-Y (6 pts), +8 (5 pts), mar (3 pts), der 12p (2 pts), and -1, +6, der 9p, del
10q, der 11p, +15, der 17q, -18, t(3;11), and t(12;14). Characteristic of two
groups (CA- vs CA+) were analysed: no significant difference was seen
according to age, sex, prior treatment, Sokal index and cytogenetic
response. However, the kinetic of bcr-abl transcript decrease was significantly
faster in the group of pts without CA. Furthermore, hematologic
or cytogenetic relapse and blast crisis occurred in 13/32 pts (41%) and
11/58 pts (19%) in CA + and CA – groups, respectively (p