Haematologica 2003 - Supplements

levels, 11q abnormalities and the presence of chromosome 13
deletions and/or monosomy (P=0.8). Overall, cyclin D1
overexpression was detected in 32 out of 74 (43%) patients. The
expression of.cyclin D1 was also correlated with the presenting
clinical features and disease outcome in the entire series of 74
patients. There was no difference in terms of age, gender,
immunoglobulin isotype and concentration, stage, creatinine,
bone marrow plasmacytosis, serum -2-microglobulin and C-
reactive proteine levels between patients who overexpressed
cyclin D1 (group A; n=32) and patients who did not overexpress
(group B; n=42). On intention-to-treat basis, the probabilities of
attaining stringently defined complete remission following
autotransplant(s) were similar for both these groups. At a median
follow-up of 34 months (range, 9–64), the median overall
survival was not reached after 48 months in group A and was 43
months in group B (P=0.6). On the other hand, patients who
overexpressed cyclin D1 had a significantly longer duration of
remission compared to patients who did not (median, 41 vs. 26
months, respectively) (P = 0.02). As a result, median event-free
survival (EFS) was longer in group A than in group B (33 vs. 24
months, respectively); the difference between the two groups was
of borderline significance (P = 0.055). It is concluded that cyclin
D1 overexpression 1) is a common molecular abnormality in de
novo MM; 2) is closely related to 11q abnormalities and 3) does
not predict for poor prognosis, as previously emphasized, rather
identifying a subset of patients who are more likely to have
longer duration of remission and extended EFS following
autotransplant(s).
Supported by MIUR, FIRB project RBAU012E9A_001 (M.
Cavo), Università di Bologna, Progetti di Ricerca ex-60% (M.
Cavo) and Fondazione Carisbo.
174
The network of cytokines in multiple myeloma:
diagnostic, prognostic and therapeutical implications
Lauta Vito Michele
Department of Biomedical Sciences and Human Oncology -
Section of Internal Medicine and Clinical Oncology
The study of the network of cytokines seems to be useful in
multiple myeloma. IL-6 and IL-2 with their soluble receptors, IL-
3, IL-4, IL-10, IL-11 have been examined. Among target cells,
growth of normal and myeloma plasmacells is supported by IL-6
together with IL-3, IL-4 and probably IL-8 and IL-10.
Differential diagnosis between multiple myeloma and
monoclonal gammopathies of undetermined significance is
generally based on clinical and laboratory parameters such as the
value of monoclonal component, bone marrow plasma cell
proportion, the serum level of different classes of
immunoglobulins and bone lesions. Nevertheless, the evaluation
of the serum level of IL-6, soluble IL-6 receptor, soluble IL-2
receptor together with the activity exerted by IL-3 and IL-4 on
some cellular subsets may be an additional element in the
differential diagnosis of border-line cases. However, concomitant
evaluation of all immunological parameters could be more useful
than the value of a single interleukin. Prognostic value of
interleukins may be considered as their most useful property as
all the interleukins involved in multiple myeloma exhibit this
significant value in different manners. Serum levels of IL-6,
soluble IL-6 receptor, soluble IL-2 receptor and the expression of
membrane-bound IL-2 receptors, both on bone marrow
plasmacells and on peripheral blood mononuclear cells, are
correlated with the disease activity and the disease stage. In
addition, IL-6 and sIL-6R serum level are correlated with the
duration of disease-free survival as a high value at the time of
diagnosis is connected to a short duration of survival. However,
some laboratory parameters may express the same prognostic
value as high β2 microglobulin and LDH serum levels together
with the high value of plasma cell labelling index are correlated
with the disease activity. Furthermore, if the evaluation is
performed at the time of diagnosis, high values of these
parameters are related to a short duration of disease-free survival.
A correlation between laboratory parameters and the serum level
of several cytokines was demonstrated. Therefore, the real
advantage of prognostic evaluation of cytokines is reserved to
patients who do not exhibit uniform results of β2 microglobulin
and LDH serum levels or better to border-line cases. Finally,
most studies indicate that interferons are mainly used in the
immunotherapy of multiple myeloma as the effectiveness of anti-
IL-6 antibodies or anti-idiotypic vaccines has not been confirmed.
175
LEVELS OF SERUM PHOSPHOLIPIDS AS PROCESS OF
SIGNAL TRANSDUCTION IN PATIENS WITH MYELOMA
N.Andjelkovich,M.Colovich.V.Jakovljevich,A.Stokovich,
P.Djurdjevich,S.Simich
Clinical hospital center Kragujevac Internal clinic, Haematology
dep.Kragujevac, Serbia and Montengro
Myeloma is very interesing field for investigation of disturbances
lipids.as reperesent of limfoproliferative malignat disorders.
Accordinig biology of disease, phopholipids disturbances is very
interesing in myeloma, as processes of signal transduction in
defect synthesis of pathological proteins. Corelation between
phopholipids an precesee of signal transduction is the aim of this
investigation.
This study included 57 patients with myeloma and 20 healthy
persons as control grop. Serum phospholipidslipids was presented
by total serum phospholipids, phospatidiletanolamin/ PE/,
sphingophospholipids, lysolecitin, phsophpatidicholin in alll
patiets and control group. Biochemical method of level detection
was thin layer chromatography/TLC/. Corelation between
phospholipid levels in idfferetn group of patients according of
Durie end Salmon clasification was the aim of study and
statistical analise presented facts:
-significant difference between group of patientis and control
group was very strong
-difference between group of pateints accordin D/S clasificatrions
was strong
-levels of lyzolecitin was higher in group of patiets in III group
ac.D/S clasification
-phosphatidiletanolamin is higher in patients with myeloma v.s
control group
-sphingophospholipids is higher in terminal phase of disease
ac.D/S clasification
Synthesis of this results shown that phospolipids in patietent
with myeloma are veru predictabl and prognostic factor of
prograsiviv disease. Process of signal transduction is definitly
damaged and depend of phase according D/S classification.
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