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

medullary involvement of multiple myeloma and was helpful in differentiating
between post therapeutic changes and residual/recurrent tumor
cells also in assessing response to therapy. In six patients PET demonstrated
a favorable treatment response by showing a decline in lesion
metabolic activity. In another patients PET showed progression of disease,
by demonstrating diffuse or focal bone lesions or higher lesion glucose
metabolism, concordant with the clinical evaluation. Conclusions.
FDG PET is able to detect bone marrow involvement in patients with
multiple myeloma. FDG PET is useful in assessing extent of disease at
time of initial diagnosis, contributing to more accurate staging. FDG PET
is also useful for evaluating therapy response. PET can detect the extent
of marrow involvement in multiple myeloma patients and is very useful
in monitoring of the treatment results.
1533
LIPOSOMAL ANTHRACYCLINES IN THE TREATMENT OF MULTIPLE MYELOMA
A. Gagliardi
ASL NA 1 Ospedale S.Giovanni Bosco, NAPOLI, Italy
Backgrounds. Not pegylated liposomal doxorubicine (Myocet) shows a
better pharmacokinetic profile and a much lower cardiological toxicity
than conventional anthracyclines. Methods. In Our Department, from
October 2003 to October 2006, we have treated 24 patients affected by
Multiple Myeloma (MM), either at a first line approach (n=13) or in resistant
and relapsed disease (n=11). At admission diagnosis concerned
patients with IgG Myeloma (n=20), IgA Myeloma (n=3) and micro-molecular
Myeloma (n=1). All the patients have been treated with one or more
cycles according to chemiotherapic scheme: VCR 1mg iv at day 1 +
Myocet 25mg/sm iv at day 2 + CTX 100mg/sm iv days 1-4 + PDN
60mg/sm os days 1-4. In all patients Monoclonal Component (MC) and
Left Ventricular Ejection Fraction (LVEF) have been assessed in order to
evaluate treatment efficacy and cardiotoxicity of liposomal anthracycline
administered. Results. We have evaluated 24 patients (12 M, 12 F), mean
age 68.71±7.96 years (50 min., 82 max.), mean baseline MC
2488.00±1791.74 and mean baseline LVEF 56.04±6.4%. Evaluation of
treatment efficacy has been made in 24 patients: MC has been reduced
from 2488.00±1791.74 to 1981.30±1240.86 (CR 49%, PR 17%, NR 13%,
PD 21%). The possible Myocet cardiotoxicity has been evaluated by
assessment of LVEF: before therapy, the mean value was 56.04±6.4% and
slightly lowered to 54.08±5.90% (p=ns) as a sign of cardiac function maintenance.
Conclusions. Treatment with liposomal anthracycline (Myocet)
lowers MC in patients with MM and leaves cardiac function unaltered.
1534
PROGNOSTIC IMPACT OF NORMAL KARYOTYPE IN CHRONIC LYMPHOCYTIC LEUKEMIA.
CLASSICAL CYTOGENETIC ANALYSIS OR FISH?
A. Athanasiadou, K. Stamatopoulos, G. Papaioannou, M. Gaitatzi,
C. Vadikolia, Z. Lazarou, I. Athanasiadou, R. Saloum, A. Fassas,
A. Anagnostopoulos
G. Papanicolaou Hospital, THESSALONIKI, Greece
Cytogenetic analysis of chronic lymphocytic leukemia (CLL) patients,
despite inherent technical limitations, has provided important information
on disease biology and clinical outcome. FISH analysis is more sensitive;
however, it only covers regions often involved in numerical or
structural rearrangements and, therefore, does not allow assessment of
the entire karyotype. We evaluated 86 CLL patients with normal karyotype
by interphase FISH and explored possible additional prognostic
information. Study group: 55 males/ 31 females, median age: 62,5 years,
Binet stage-A/B/C: 65/17/4/ median time from diagnosis to cytogenetic
testing: 4,8 months/ median follow-up time: 36.8 months. CD38 expression:
21/86 cases (24.5%)/ unmutated IGHV genes (U-IGHV): 28/86 cases
(33%; 17/28: Binet-A). The FISH panel included probes for detection
of trisomy 12 and deletions of 13q14/11q22.3/17p13. Deletion 13q14
was detected in 33/86 cases (38,4%); 12/33 carried biallelic deletions. Trisomy
12 (+12) was detected in 4/86 cases. Deletions 11q22.3/17p13
were identified in, respectively, 2/86 and 1/86 cases, who also carried
del(13)(q14). Forty-nine cases (57%) were not found to carry cytogenetic
aberrations on FISH analysis. Patients were divided in four subgroups:
(i) normal karyotype/FISH; (ii) +12; (iii) isolated del13q14; (iv) 11q-17p
aberrations. The four subgroups were not significantly different with
regard to age/sex/clinical stage at diagnosis. On univariate analysis,
advanced clinical stage, CD38 expression and U-IGHV genes were associated
with a shorter progression-free survival (PFS). CD38 expression
and U-IGHV genes were significantly more frequent in +12 cases
(p=0.0001/ p=0.002, respectively). Patients with +12/11q-17p had signif-
12 th Congress of the European Hematology Association
icantly shorter PFS (Log rank test=0.0007). Biallelic del(13)(q14) did not
affect prognosis. On multivariate analysis, only U-IGHV genes and
advanced clinical stage were found to adversely affect prognosis
(p=0.001/ p=0.0001, respectively). In conclusion, interphase FISH analysis
of CLL patients significantly increases the detection rate of cytogenetic
aberrations. The most frequent abnormality on FISH analysis in
normal karyotype cases was del(13)(q14), which did not affect prognosis.
This finding suggests that del(13)(q14) could very likely represent a
secondary event associated with disease evolution.
1535
HUMAN HEART-TYPE FATTY ACID-BINDING PROTEIN AS AN EARLY DIAGNOSTIC
MARKER OF DOXORUBICIN CARDIAC TOXICITY
A. Elghandour, 1 S. Azab, 1 M Abd El Rahaman2 1 2 Faculty of Medicine, ALEXANDRIA; Military Medical Academy, ALEXAN-
DRIA, Egypt
Background. Late cardiac toxicity following treatment with doxorubicin
in patient with non-Hodgkin’s Lymphoma may lead to latent cardiomyopathy.
So, early prediction of toxicity can lead to prevent the occurrence
of heart failure. Aim. the aim of this work was to investigate the clinical
applicability of H-FABP as early diagnostic marker of chemotherapy
induced cardiac toxicity. Patients and Methods. This study enrolled 10 normal
controls and 40 patients with non-Hodgkin’s lymphoma (NHL)
received chemotherapy based doxorubicin for 6 cycles (one day CHOP)
not exceeded total allowed dose. Human heart-type fatty acid-binding
protein (H-FABP) was assessed 24 hours post first cycle of chemotherapy.
Plasmatic levels of brain natriuretic peptide (BNP) were measured at the
end of chemotherapy cycles. Resting echocardiography was done before
starting chemotherapy and after last cycle. Results. follow up examination
echocardiography showed that ejection fraction (EF) of nine patients
decreased below 50% while eighteen patients demonstrated diastolic
dysfunction. Elevated levels of both H-FABP and BNP were found in all
patients with decreased EF and diastolic dysfunction, positive correlation
was found between them. Conclusion. our study showed that H-FABP
may serve as early prediction reliable marker for latent myocardial damage
secondary to doxorubicin chemotherapy which may be of practical
importance in preventing heart failure in future with subsequent planning
for alternative chemotherapy modalities with no cardiac toxicity.
1536
THE PROGNOSTIC SIGNIFICANCE OF THE EXPRESSION OF UROKINASE PLASMINOGEN
ACTIVATOR RECEPTOR (UPAR) ON ACUTE MYELOID LEUKEMIA CELLS
M. Cioch, M. Jarosz, A. Dmoszynska
Medical University of Lublin, LUBLIN, Poland
Introduction. The receptor for urokinase plasminogen activator (uPAR;
CD87) expressed by many normal and malignant cells is an important
component of cell migration, adhesion, chemotaxis and tumor-cell invasion.
Over-expression and negative prognostic role of uPAR has been
reported in many malignant tumors. There are less reports on the role of
uPAR in hematologic malignancies, especially in acute leukemias. The aim
of this study was to determine the prognostic significance of the expression
of uPAR on acute myeloid leukemia (AML) cells. Material and methods.
Thirty seven patients (pts: 20 males and 17 females) were included
in the study. They were treated with induction therapy acc. Polish Adult
Leukemia Group (PALG) programme. The uPAR (CD87) expression was
measured by labelling fresh viable bone marrow cells with anti-CD87
monoclonal antibody (Chemicon) and analysis in FACSCalibur flow
cytometer. Results. The mean expression of uPAR on bone marrow blast
cells was 44.67% (from 10.1% to 94.4%; SD=26.77%). There was no correlation
between uPAR expression and sex, age of pts and type of AML.
We found positive correlation between uPAR expression and the expression
of CD4 (p=0.049), VCAM-1 (p=0.035) and MDR1 (p=0.002). Twenty
one pts obtained CR after one or more induction therapy, but 16 pts
never had CR. There was no statistical significant difference in uPAR
expression between pts with CR and pts without CR (p=0.87). We found
correlation between uPAR expression and disease free survival (DFS), but
without statistical significance (p=0.056). There were statistical significant
correlation between uPAR expression and overall survival (OS) (p=0.028).
Conclusions. The correlation between uPAR and CD4 and also VCAM-1
expression confirm the role of uPAR in blast cells migration, adhesion and
invasion. The unfavorable prognostic importance of uPAR expression is
suggested by correlation between uPAR and MDR1 expression and statistical
significant influence on OS.
haematologica/the hematology journal | 2007; 92(s1) | 543