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

even when ADP-induced plt activation varies considerably from one
individual to one, as observed by other groups. b) Patients with ACS
present less response to plt agonist showing less degree of plt activation
due to antiplatelet drugs administration. c) Flow cytometry represents an
useful method to measure effect of antiplatelet drugs according to our
results, altough more studies are nedeed.
1526
SECONDARY HEMOSIDEROSIS, IRON DEPLETION AND HEPATITIS C VIRAL LOAD
M. D’Onofrio, 1 L. Paesano, 1 I. Gentile, 2 C. Viola, 2 E. D’Agostino, 2
M. Piazza, 2 G. Borgia, 2 S. Formisano2 1 Hospital S. Giovanni Bosco, NAPLES; 2 University Federico II, NAPLES, Italy
Background. Iron overload is observed in about 30% of patients affected
with chronic hepatitis HCV-related. Although relations between
hemosiderosis, HCV genotype and viral replication do not seem to exist,
some studies have suggested that plasmatic and tissual iron levels may
be related with hepatic inflammation and with fibrogenesis. Aims. Aim
of this study has been to detect an eventual reduction in viral replication
consequently to modification in hematological parameters after a therapeutic
cycle of blood letting, performed, in order to reduce the secondary
iron overload, in patients affected with HCV-RNA+ chronic hepatitis.
Methods. In 19 patients, enrolled and treated in University, the iron
overload has been evaluated by assaying ferritin, plasmatic iron, total
iron binding capacity (TIBC) and transferrin saturation (TS). The most
frequent genetic mutations of HFE gene (C282Y e H63D) were searched;
moreover HCV-RNA load and HCV genotype were also investigated.
The patients have been treated by phlebotomy, taking away 400-450 mL
of whole blood every week. The laboratory evaluation has been performed
before starting the treatment (time 0), and after a follow up of 7
days (time 1) and of 30 days (time 2) after the last phlebotomy. The statistical
analysis has been performed by the Wilcoxon test. Results. At
time 0, patients showed these values (mean±SD): Ferritin=399±244
ng/mL, Iron=146±27 µg/mL, TIBC=350±48 µg/mL, TS=43±6%. Genetic
mutations for C282Y were absent either in homozygosis either in heterozygosis,
while 4 patients were heterozygote for H63D. The patients
have been submitted to a mean of 5±2 blood letting. At sequent controls,
Ferritin levels significantly decreased (51 at time 1, p=0.0002; 39 at time
2, p=0.0004); Iron also significantly decreased at time 1 (=63, p=0.0008),
but not at time 2 (87, p=0.06); TIBC showed no statistical significant
variations; moreover TS significantly decreased between time 0 and 1
(p=0.001) and it did not significantly go up at time 2 (p=0.059). Viral typing
resulted: genotype 1 for 16 viruses, genotype 2 in 1 case, as genotype
3 and 4. Viral load has not been significantly influenced by phlebotomy
(time 0: 657.500 UI/mL and time 2: 655.805, p=0.47). Conclusions. Blood
letting results effective in the treatment of hemosiderosis, permitting a
rapid iron depletion; this is not limited to period of therapeutic cycle, but
it is maintained, on the basis of our data, at least for a follow up of
47.7±13.9 days. From a clinical point of view, patients refer a generic
improvement of general health conditions. Our results demonstrate that
iron overload, in our patients, is certainly secondary, in fact only 4 subjects
carried a minor HFE mutation, but this was unable alone to determine
hemosiderosis because present in heterozygosis. Moreover we
have observed a total indifference of viral load, independently by viral
genotype, to phlebotomy treatment, demonstrating that blood letting
represents a valid therapy to prevent some complications of viral infection
but it is not of aid in the treatment of primary pathology, linked at
active viral replication.
1527
A PHASE II STUDY OF THALIDOMIDE PLUS BOLUS VINCRISTINE/ADRIAMYCIN AND
MODIFIED DEXAMETHASONE COMBINATION THERAPY FOLLOWED BY AUTOLOGOUS
STEM CELL TRANSPLANTATION FOR MULTIPLE MYELOMA: PRELIMINARY DATA
J.-Ch. Jo, S. Kim, B.W. Kang, S.S. Lee, S.J. Sym, G.D. Jang, C. Suh
Asan Medical Center, SEOUL, South-Korea
Background. High-dose chemotherapy supported by autologous stem
cell transplantation (ASCT) after the combined chemotherapy with vincristine,
doxorubicin and dexamethasone (VAD) for initial cytoreduction
is effective therapy for newly diagnosed, symptomatic multiple myeloma
(MM). Bolus vincristine/doxorubin intravenous infusion as an outpatient
route is convenient and is acceptable efficacy and toxicity. Thalidomide
has recently shown significant antimyeloma activity. Aims. We studied
the efficacy and toxicity of the combination of bolus administrating
vincristine/doxorubicin and reduced-dose of dexamethaxone with
thalidomide, administered on an outpatient basis, as initial cytoreductive
12 th Congress of the European Hematology Association
treatment in previously untreated patients with symptomatic myeloma.
Methods. Twenty-six myeloma patients were treated with vincristine 0.4
mg intravenously (i.v.), doxorubicin 9 mg/m 2 (i.v.) administered as single
dose on day 1, and dexamethasone 20 mg per os daily for 4 days. Dexamethasone
was also given on days 8-11, 15-18 of the each cycle of treatment.
The regimen was administered every 4 weeks for three courses.
Thalidomide was given daily at a dose of 200 mg at bedtime. Response
to treatment was evaluated after each cycles of treatment. After completion
of three cycles, the patients were allowed to proceed to high-dose
chemotherapy with ASCT or to receive further chemotherapy including
changed regimen. Results. On an intention-to-treat basis, 23 of the 26
patients (88.4%) responded to treatment. Sixteen patients (61.5%)
achieved complete and seven (26.9%) partial response. Only two (7.6%)
were rated as non-responders. In total 78 cycles, major grade 3 or 4 toxicities
consisted of neutropenia (8.9%), neutropenic fever (6.4%), anemia
(7.6%), thrombocytopenia (3.8%) without significant nonhematologic
event including cardiomyopathy and peripheral neuropathy. But, ten
patients (38.4%) experienced pneumonia and one patient (3.8%) deep
vein thrombosis during this regimen. In twelve patients who received
ASCT, the event free survival was 67% and the overall survival was 100%
for one year. Conclusions. In initial cytoreductive treatment, the combination
of bolus administrating vincristine/doxorubicin and reduced-dose of
dexamethaxone with thalidomide would be expected to have exellent
efficacy and be relatively well-tolerated. Now this study for previously
untreated MM is going to enroll more number of patients.
1528
THE IMPACT OF AGE AND SEX ON GAMMA-DELTA T LYMPHOCYTE PREVALENCE
IN PERIPHERAL BLOOD OF MULTIPLE MYELOMA (MM) AND LYMPHOMA MALIGNUM
(NHL) PATIENTS
E. Sowinska, L. Usnarska-Zubkiewicz, K. Kuliczkowski
Wroclaw Medical University, WROCLAW, Poland
Background. Gamma-delta T lymphocytes (gd T) constitute average
4% of all T lymphocytes population in peripheral blood. Activated gd T
cells express antigens CD 25 + (late activator) and CD69 + (early activator)
on their surface. They appear to posses an intrinsic cytolytic activity
against tumor cells in carcinomas, sarcomas, acute lymphoblastic
leukemia and lymphomas. Statistically, higher multiple myeloma (MM)
morbidity among men and higher lymphoma malignum (NHL) morbidity
in women was documented. Aims. Comparison of gd T cell mean percentage
(%) in peripheral blood of MM and NHL patients (pts) regarding
age and sex discrepancies. Material and Methods. A total of 59 pts:
35 of MM and 24 of NHL, treated in Department of Hematology, Blood
Neoplasms and Bone Marrow Transplantation of Wroc∏aw Medical
University and 14 healthy controls were included into analysis. 35 MM
pts: 8 pts were in stage I, 6 in II and 21 in III stages, according to Durie-
Salomon classification; sex: F/M- 23/12, age: 42-77, Me=62 years. 24
NHL pts: 2 were in I, 2 in II, 2 in III and 18 in IV stages according to Ann-
Arbor classification; sex: F/M-11/13, age: 20-85, Me= 65 years. Samples
of blood were taken at the time of MM and NHL diagnosis. gd T cells
were estimated by flow-cytometry (FACS), using a fluorescence-activated
cell sorter and monoclonal antibodies: MoAbs:Ab-anti TCRgamma1-
FITC (Becton-Dickinson), anti CD14-RPE, anti CD-45-FITC, anti CD25-
RPE, anti-CD69-RPE and Ab IgG1- RPE as negative controls ( DAKO ).
Results. gd T lymphocytes mean% in peripheral blood of MM pts was
higher than in NHL pts (4,33 vs 2,73, p=0,05); moreover in both pts
groups is lower than in control healthy group: MM: 4,33 vs 5,63, p=NS,
NHL: 2,73 vs 5,63, p=0,0003. In 23 MM women gd T % in blood was
higher than in 12 MM men: 4,44 vs 4,14, whereas in 11 NHL women it
was lower than in 13 NHL men: 2,48 vs 2,93. In MM higher activated
gd T CD25 + mean % in female than in male sex was observed: 0,19 vs
0,05, p=0,07. There were no differences in activated gdT CD25 + lymphocytes
number in blood between male and female sex in NHL and in
healthy individuals: 0,08 vs 0,11 and 0,07 vs 0,06,respectively. Activated
gd T CD69 + mean % in MM women was higher than in MM men:
0,65 vs 0,38, whereas in NHL women mean % of these cells was lower
than in men 0,48 vs 0,7. Statistically significant negative correlation
between gd T cells % and NHL pts age was found, r=-0,42, p=0,04. Conclusions.
Lower gd T lymphocyte number in peripheral blood in MM and
NHL pts, compared to healthy individuals, is probably due to gd T cells
migration from peripheral blood to other tissues included in tumor
process, where these cells directly eliminate tumor cells. Higher multiple
myeloma morbidity among men and higher lymphoma malignum
morbidity in women may be result from dissimilar gd T lymphocyte
antitumour cytolytic activity disorders, occurred in men and women,
predispose given sex to MM or NHL development.
haematologica/the hematology journal | 2007; 92(s1) | 541