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

12 th Congress of the European Hematology Association
and least toxicity with the BEACOPP principle for the treatment of
advanced stage HL. Recently, an interim FDG-PET study was suggested
that FDG-PET after two cycles of CT is the most powerful tool available
for predicting treatment outcome in HL Purpose: To evaluate the efficacy
of a time-dense regimen BEACOPP-14 in naïve patients with advanced HL
They were assigned to therapy according to defined risk. Patients were
defined depending on the International Prognostic Score (IPS). Those with
IPS of 3 or higher received 2 cycles of BEACOPP-14 making a FDG-PET
after them in order to decide the total cycles. Design: observational,
prospective trial in a consecutive and previously untreated patients diagnosed
of HL non Lymphocyte Predominant with advanced stage in one
centre. Exclusion criteria: HIV positivity, other malignancies and CNS
involvement. Patients and Methods. Since September 2005 to December
2006, 10 patients were included in a bleomycin, etoposide, doxorubicin,
cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP-
14) regimen administered in outpatient setting. At baseline assessment:
demographic data, clinical and physical exam, blood counts, serum and
urine biochemistry, body scan, bone marrow biopsy. Patients were classified
according IPS and clinical stage. All patients receiving prophylaxis
with pegilated granulocyte factor on day +4. Response was evaluated by
FDG-PET after 2 cycles and classified as: complete remission (CR), partial
remission (PR), and non response (NR). Patients with CR received 2 additionally
cycles and patients on PR 6 cycles. Adverse effects were registered.
Statistical analysis: Survival analysis was performed using Kaplan-Meier
and Cox regression. Overall survival (OS), relapsed free survival (RFS).
Results. 9 valuable classic HL patients Mean age 27.6 y (17-51), male 6 and
female 4. IPS 4 (3), 5(4). Bulky disease 2 patients. 1). FDG-PET after 2
cycles: positive 4 patients, negative 5. Total cycles: 4 in 4 patients, 8 in 3.
Response (5 valuable patients): 3 CR, 1 PR, 1 NR. Toxicity: anaemia 6 (all
received erythroid agents), neutropenia 1, respiratory infection 2, erythema
1, peripheral neuropathy 1, acute hearth infarction 1. Cycles delayed:
10 in 5 patients. Early relapse: 1 (on 6 month). No death have been
observed. Mean OS was 6.6 months (2-12) and mean RFS 5 (1-9). Conclusions.
Overall response has been 80% (CR60%). Adverse events are frequent
(78%) and we had to delay cycles in 50% of patient by myelotoxicity.
It necessary more patients and a longer follow-up to know the effectiveness
of BEACOPP-14 and the value of FDG-PET after 2 cycles of BEA-
COPP-14 to predict response.
1305
RESPONSE TO BORTEZOMIB IN RELAPSED/REFRACTORY MULTIPLE MYELOMA COHORT
A. Rubio-Martinez, 1 V. Recasens, 2 M.A. Montañes, 2 P. Mayayo, 2
P. Delgado, 2 J.C. García-Zueco, 2 D. Rubio-Félix, 2 P. Giraldo2 1 Hospital U Miguel Servet, ZARAGOZA; 2 Haematology Department. HU
Miguel Servet, ZARAGOZA, Spain
Background. Bortezomib has been shown to be effective in multiple
myeloma (MM), but there is limited experience in response to re-treatment.
Aims. To evaluate the efficacy and safety of Bortezomib in an
every day clinical use in refractory/relapsed MM between December
2003 to November 2006 in a single institution. Patients and Methods. 43
patients with relapsed/refractory MM receiving Bortezomib alone (1,3
mg/m 2 on days 1,4,8,11 in a 21-day course) as second or more line of
therapy. The response was evaluated according EGBMT criteria (Bladé
J, Samson D, Reece E et al.). Patients without response after 4 courses and
patients that relapsed after reached CR or PR with Bortezomib alone, a
combination of bortezomib + dexamethasone (BD) or bortezomib+melphalan+prednisone
(BMP) were administered. Adverse effects were registered.
Results. 43 patients (males 41.8%), mean age 67.3 years (34-89),
over 65 years (51.1%). Bortezomib was administered in second line: 14
(32.5%), in third or more: 29 (67.4%). Overall response: 31 (77.5%);
CR+PR: 29 (72.5%); MR: 2 (5.0%); CR: 16 (40.01%); CR-EIF negative:
11 (27.5%); failure: 9 (22,5%), mean courses to reached response: 3.6.
No relation to response and presence or not chromosomal aberrations.
At 36 months on follow-up, of 40 valuable patients, 18 (45%) are in stable
response without therapy. Seven patients (16.3%) do not reached
response after 4 courses and received a Bortezomib combination therapy,
10 patients (23.2%) were relapsed after a mean of 18 months followup
in stable response. In 12 patients (70.5%) a combination of BD was
applied and 5 patients(29.5%) received BMP by relapse or progression.
Responses: group BD 1 CR EIF+, 7 PR, 4 F; group BMP 1 CR-EIF-, 2 PR,
1 F, 1 NV. 14 patients died by progression or infectious complications
(35%). Adverse events. thrombocytopenia 40% (grade III: 20), fatigue
25%, peripheral neuropathy 37.7%, constipation 35%, diarrhoea 22.5%,
ZHV 15%, non documented infection 35%, fever 12.5%, hypotension
5%, leucopenia grade 3 15%. Only 3 patients (7.5%) need disrupted
therapy by toxicity. No more adverse events were observed in patients
472 | haematologica/the hematology journal | 2007; 92(s1)
treated with bortezomib in combination. Comments. In our experience
a high response to Bortezomib in an every day clinical use in
relapsed/refractory MM was observed. In addition re-treatment with
Bortezomib in combination induces response (64.7%). The safety is
good with tolerable adverse effects. It is necessary prolonged follow-up
time and to perform more studies in order to establish the best schedule
for relapsed/refractory MM.
1306
EXPRESSION OF THE MICROVESSEL DENSITY, GP-130, VCAM-1, AND KI67 WITHIN
THE BONE MARROW COMPARTMENT IN MULTIPLE MYELOMA
M. Perunicic Jovanovic, J. Bila, Lj. Jakovic, T. Terzic, D. Tomin,
M. Gotic, D. Boskovic
Institute for Haematology KCS, BELGRADE, Serbia
In multiple myeloma (MM), the interaction between myeloma cells
and bone marrow microenvironment has an important role in the pathogenesis
of MM. The functional interplay between the myeloma cells
and the surrounding microenvironment within the bone marrow (BM)
includes increased activity of endothelial cells resulting in neovascularisation,
and enhanced sensitivity to the IL-6 as a main growth factor in
multiple myeloma (MM). This cytokine, as a member of gp130 family,
binds on the surface of myeloma cells to the IL-6 receptor gamma chain
that associates with the gp130 transducer chain providing the proliferation
signal to the tumor cells. VCAM-1 is adhesion molecul from the
immunoglobulin gene superfamily. High proliferative rate has been associated
with worse survival. The aim of study was to investigate the correlation
between expression of BM angiogenesis estimated as microvessel
density (MVD), and expression of the transmembrane signal transducer,
gp130, VCAM-1 , and proliferative rate of the myeloma cells in
the bone marrow of MM patients (pts). The study included 60 newly
diagnosed MM pts (33 male and 27 female pts, mean age 60 years, range
35-75). According to the clinical stage (CS, Salmon&Durie), distribution
of MM pts was as follows: I 8pts, II 22pts, III 30pts. There were 35pts
with IgG monoclonal (m) protein, 12pts with IgA, and 12pts with secretion
of kappa/lambda chain. Renal failure had 17 pts. All pts were treated
with standard chemotherapy regimens. BM vessels were visualized
by immunohistochemical staining for CD34 on slides of formalin-fixed,
paraffin-embedded BM biopsies. MVD was calculated by the number
of vessels per 400x high-power microscopy field in the area of the most
dense vascularization. All samples were further analyzed for the
immunohistochemical expression of the gp130, VCAM-1 which showed
cytoplasmic and membrane localization. The intensity of these stainings
was graded as weak (0-30% myeloma cells), moderate (31-60% myeloma
cells), and strong (>60% myeloma cells). We also analyzed the percentage
of Ki67 + MM cells. According to the CS of myeloma, positive
correlation was found between MVD and expression of GP130 in
myeloma cells. The expression of MVD was significantly higher in MM
pts in III CS than in pts in I CS of myeloma (15 vs. 7,5/ x400 field,
p< 0.001). Similarly, significantly higher expression of gp130 was found
in pts in III CS of myeloma comparing to the MM pts in I CS (32 vs.15%,
p