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

phamide 750 mg/m 2 on day 1, vincristine 1.4 mg/m 2 on day 1, and oral
prednisone 100 mg/d on days 1 to 5, preceded on day 1 by Rituximab
375 mg/m 2 . This regimen were repeated every 21days for six cycles.
Granulocyte colony-stimulating factor (G-CSF) and Pneumocystis Carinii
prophylaxis was given. PCR molecular analysis was performed in 14
patients at diagnosis showing in 14 (70%) of them bcl-2 rearrangement.
Results. Arm R-FMD: Out of all patients, 19 and 1 achieved CR and PR,
respectively. The patient in PR achieved CR after Zevalin. Actually, after
a median follow up of 28 months, all patients resulted in CR. At the end
of treatment, bcl-2 appeared to be negative in 15/20 pts (75%). The toxicity
was mild with grade 3-4 neutropenia in 6 pts (30%). CMV infection
was observed in 1 patient. Arm R-CHOP: Ninenteen patients
achieved CR and 1 resulted non responder. Out of all 19 pts in RC: 1 died
in CR for infection and 1 relapsed after 23 months. After a median follow
up of 28 months, 18 patients are still alive and 17 of which are in
continue CR. Grade 3-4 neutropenia was observed in 4 (28%) pts. At the
end of treatment bcl-2 appears to be negative in 6/9 pts (66%). Conclusions.
Our data demonstrate that both frontline R-FMD and R-CHOP
treatments produce high rate of response in terms of CR, OS and molecular
remission (although a more positive trend was observed in R-FMD
Arm) and had very low toxicity. A prolonged follow-up will be needed
to determine the long-term efficacy of these combinations.
1302
R-COMP VS R-CHOP IN THE TREATMENT IN NEWLY DIAGNOSED ELDERLY PATIENTS
WITW AGGRESSIVE NON-HODGKINS LYMPHOMA
M. Dell’Olio, C. Bodenizza, A.M. Carella, A. Falcone, M.M. Greco,
A. La Sala, S. Mantuano, L. Melillo, E. Merla, M. Nobile, G. Sanpaolo,
P. Scalzulli, N. Cascavilla
Casa Sollievo della Sofferenza Hosp., SAN GIOVANNI ROTONDO, Italy
Background. Conventional anthracyclines are active in non-Hodgkin’s
lymphomas(LNH), but cardiotoxicity related to the cumulative dose may
limit their use. Preclinical studies determined that encapsulating conventional
anthracyclines in liposomes can reduce the incidence and
severity of cumulative dose-related cardiomyopathy while preserving
antitumor activity. Aims. In this study we have evaluated the impact of
R-COMP as compared to R-CHOP as a first line therapy in newly diagnosed
ederly patients with aggressive LNH, in terms of complete
response (CR), overall survival (OS) and toxicity (especially cardiac safety)
substituting for conventional doxorubicin with non-pegylated liposomal
doxorubicin (Myocet) in the CHOP regimen. Methods. Between
January 2005 and June 2006, 40 pts with aggressive LNH were enrolled
in the study. Twenty patients : M/F 11/9, median age 69 years (range 57-
81) received R-COMP treatment in stage III-IV, IPI score: intermediate
grade 13 pts, high grade 7 pts. Baselin median left ventricular ejection
fraction (LVEF) was 58(range 50-68). R-COMP regimen was administered
every 21 days for six cycles: Rituximab 375 mg/m2 day 1,
Cyclophosphamide 750 mg/m2 day1, Myocet 50 mg/m2 day 1, Vincristine
mg/ m2 day 1, and oral Prednisone 100 mg/d on day 1-5. Twenty
patients: M/F 8/12, median age 66 years (range 57-70) received R-CHOP
treatment in stage III-IV, IPI score: intermediate grade 14 pts, high grade
6 pts. Baseline median LVEF was 62% (range 55-70). The CHOP regimen
consisted of Doxorubicin 50 mg/m2 on day 1, Cyclophosphamide 750
mg/m2 on day 1, Vincristine 1.4 mg/m2 on day 1, and oral Prednisone 100
mg/d on days 1 to 5, preceded on day 1 by Rituximab 375 mg/m2 . This
regimen were repeated every 21 days for six cycles.Granulocyte colonystimulating
factor and Pneumocystis Carinii prophylaxis was given in
both regimen. Results. Arm R-COMP: An overall response 15 (75%)CR,
4 (20%)PR and 1(10%) NR was achieved in all patients. After a median
follow up of 13 months, all 20 (100%) pts resulted alive. At the end of
treatment, LVEF median was 57,50% . Any cardiac event in relationship
to the therapy.The toxicity was mild with grade 3-4 neutropenia in 4 pts
(20%). Arm R-CHOP: 14 pts (70%) achieved CR , 4(20%) PR, and
2(10%) resulted non responder. Out of all 14 pts in RC: 1 died in CR for
infection, 1 relapsed after 10 months. After a median follow up of 13
months, 19 (95%) pts are alive, 12 (60%) of which are in continue CR.
Grade 3-4 neutropenia was observed in 4 (28%) pts. At the end of treatment
LVEF median was 58%. Conclusions. The substitution of Doxorubicin
with Myocet into the R-CHOP regimen (R-COMP) at an equivalent
dose is anapplicable and active regimenn in elderly patients with
newly diagnosed aggressive LNH and the significant difference in median
post-chemotherapy LVEF (R-COMP 58>57,5; R-CHOP 62 > 58), show
a lower cardiotoxic effect. A long-term follow up and more patients will
be necessary to confirm our preliminary observations.
12 th Congress of the European Hematology Association
1303
OVER AND DOWN EXPRESSION OF GENES TRIGGER THE ACTIVATION
OF DIFFERENTIATION AND PROLIFERATION OF SIGNALLING PATHWAYS IN PLASMA
CELLS OF MULTIPLE MYELOMA
M. Ortega
State University of Campinas (UNICAMP), CAMPINAS, SÃO PAULO,
Brazil
Background. The molecular mechanisms involved in multiple myeloma
(MM) are still not completely clarified. Recent leaps in comprehension
of the intracellular pathways and the complex interaction with the
bone marrow microenvironment have contributed for elucidating its
physiopathology. We previously studied the global gene expression in
malignant plasma cells (MPC) by serial analysis of gene expression
(SAGE) and found abnormalities in expression of several genes potentially
involved in disease. Aims. In the current study, we selected and
quantified the expression of nine genes (IL6-ST, CD19, CD40, PRDM2,
CFOS, FOSB, DUSP1, CJUN and CCND1) with potential action in MPC
maturation, proliferation, and survival. Methods. Purified samples of MPC
and normal plasma cells (NPC) were obtained from 14 MM patients and
one healthy control using the CD138 antibody MACS microbeads and
column magnetic sorting. The gene expression was investigated in MPC
and NPC by quantitative polymerase chain reaction real-time (RT-PCR)
using the B-actin and GADPH genes to normalise reactions. The cut off
ratio for the comparison of profiles was set as 2-fold over expressed or
2-fold under expressed for each gene, with a statistical likelihood of
p