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

ecause some of the patients were originally misdiagnosed in other clinics
as thalassemia major and were started early on regular transfusion.
Results. The overall analysis population was formed of 92 patients out of
a total of 109. Females comprised 51.1%. All patients are born in the
time period between 1970 and 2004. Average serum ferritin for patients
without complications was lower than those with complications
(911±771 vs. 1347± 764). In the survival analysis, the most recent birth
cohorts (after 1994) had a more extended complication free period
(p=0.009) with no reported complications. There are 44 patients born
before 1983 and 31 patients born between 1984 and 1993. There is significant
difference in the complications of both groups with a far worse
disease progression for those born between 1984 and 1993 (p=0.003).
Male gender seems to confer worse disease free- survival than female
gender (p=0.078). Furthermore, our results have shown that one patient
suffered from congestive heart failure, and 25 patients (54.3%) sustained
pulmonary hypertension. The other frequent complications are
endocrinologic, with hypogonadism affecting 10.9% of patients (n=10)
and hypothyroidism present in 9.8% (n=9). Of the 109 patients who had
their charts reviewed, 79.8% were splenectomized and 43.1% were on
chelation therapy. After crossmatching each complication with splenectomy
and chelation separately for any possible relationship, hypothyroidism
versus splenectomy was significant with all splenectomized
patients developing hypothyroidism as a complication (p=0.049). Conclusions.
Survival analysis of thalassemic groups is difficult. Traditional
Kaplan-Meier survival analysis requires all patients be followed from
birth and have similar exposure during follow up. The presence of a single
care center has annulled the issue of exposure and follow up. There
is significant difference in the complications of both groups with a far
worse disease progression for those born between 1984 and 1993
(p=0.003). The most common complications reported among Lebanese
thalassemics are attributed to pulmonary hypertension (54.3%).
Endocrinologic dysfunction (hypogonadism 10.9% and hypothyroidism
9.8%), infection and thrombotic events are documented. Furthermore,
79.8% of TI patients were splenectomized and 43.1% were on chelation
therapy. Crossmatching each complication with splenectomy and chelation
separately for any possible relationship, hypothyroidism versus
splenectomy was significant with all splenectomized patients developing
hypothyroidism as a complication (p=0.049).
Table 1. Complications of TI among 92 patients.
1175
RITUXIMAB IN COMBINATION WITH DOSE-DENSE THERAPY IN DIFFUSE LARGE B-CELL
LYMPHOMA (DLBCL) AUSTRIAN WORKING PARTY MEDICAL TUMOR THERAPY (AGMT)
STUDY NHL-8
M.A. Fridrik, 1 J. Thaler, 2 G. Hopfinger, 3 U. Jäger, 4 R. Greil5 1 AKH-Linz, LINZ, Austria; 2 Klinikum Kreuzschwestern, WELS, Austria;
3 Hanusch Krankenhaus, WIEN, Austria; 4 Medizinische Universitätsklinik 1,
VIENNA, Austria; 5 Medizinische Universitätsklinik, SALZBURG, Austria
Background. For centuries polychemotherapy with cyclophosphamide,
doxorubicin, vincristin, and prednisolon (CHOP) was the standard treatment
for DLBCL. Recently the concept of dose density emerged. With
dose-dense CEOP/IMVP-Dexa (cyclophosphamide, epirubicin, vincristin,
12 th Congress of the European Hematology Association
prednisolon, ifosfamide, etoposide, methrotrexate, and dexamethasone)
we were able to improve the survival of patients with aggressive lymphomas
in comparison to CHOP. However, others have shown a
improvement of survival by adding rituxmab to CHOP. Aim of our phase
II study was to evaluate the feasibility and results of the combination of
dose-dense CEOP/IMVP-Dexa with rituximab in untreated DLBCL.
Methods. We treated 30 patients under the age of 61 years with untreated
DLBCL with R-CEOP/IMVP-Dexa: Rituximab 375 mg/qm i.v. d1+15,
cyclophosphamide 750 mg/qm i.v. d1, vincristine 1,5 mg/qm i.v. d1+8,
prednisolon 100 mg p.o d1-5, ifosfamide 2000 mg/qm i.v. d15-17, etoposide
80 mg/qm i.v. d15-17, dexamethasone 20 mg p.o. d15-19, and
methotrexate 800 mg/qm i.v. d22. Cycles were repeated every 29 days 4
times. The results were compared with an age matched historical control
group treated with the same chemotherapy without rituximab and another
age matched historical control group treated with 3-weekly CHOP.
Results. Twenty-five of 29 (86%) and 34 of 37 (91%) patients treated with
dose-dense chemotherapy with and without rituximab, respectively
achieved a complete remission (CR) or CR undetermined (Cru). Time to
treatment failure after 2 years was better for rituximab plus dose-dense
therapy (0.94 (95% CI 0.63-0.99) versus 0.72 (95%CI 0.55-0.83)), but this
difference did not reach statistical significance (p=0.06). Two year survival
was identical in both groups. Compared with 3-weekly CHOP dosedense
therapy with and without rituximab achieved an absolute benefit
in overall survival after 2 years of 30% (p=0.025). With the exception of
lymphopenia we observed no increase of toxicity by the addition of rituximab
to dose-dense therapy. Summary and Conclusions. The early results
of this trial show that the addition of rituximab to dose-dense therapy is
feasible, but it does not improve the results. Longer follow up is necessary
for final analyses of the role of rituximab in combination with dosedense
therapy. In comparison to 3-weekly CHOP dose-dense therapy
with rituximab improves survival by 30%.
1176
RITUXIMAB, GEMCITABINE AND OXALIPLATINUM: AN EFFECTIVE REGIMEN IN PATIENTS
WITH REFRACTORY AND RELAPSING MANTLE CELL LYMPHOMA
J. Rodriguez, 1 A. Gutierrez, 1 A. Palacios, 2 M. Navarrete, 2 I. Blancas, 3
J. Alarcon, 1 P. Mut, 1 A. Lopez2 1 University Hospital Son Dureta, PALMA DE MALLORCA, Spain; 2 Hospital
Vall d’Hebron, BARCELONA, Spain; 3 Hospital Clínico de Granada, GRANA-
DA, Spain
Background. Mantle cell lymphoma constitutes one of the poorest prognosis
non-Hodgkin lymphomas. The median survival is less than 3 years
and at present is incurable with conventional chemotherapy. Although
new intensive regimens and high-dose chemotherapy with stem cell rescue
give raise a higher response rate, the outcome for patients who
relapse is very poor. Moreover, due to the advanced age of presentation,
limited effective salvage regimens are available. Thus, the development
of effective regimens with acceptable toxicity in this elderly population
is warranted. Aims. To evaluate the clinical activity and toxicity of a new
salvage regimen, which combines gemcitabine, oxaliplatin, and rituximab
(GEMOX-R), in patients with relapsing or refractory mantle cell
lymphoma. Patients and Methods. Herein, 13 patients of an ongoing phase
II study for refractory or relapsing mantle cell lymphoma are reported.
GEMOX-R consisted of Rituximab (375 mg/m 2 ) on day 1, gemcitabine
1000mg/m 2 and oxaliplatin 100 mg/m 2 . Treatment was given every 15
days if feasible or every 21 days. The median number of cycles was 6.
The median age of the patients was 72 years. Seven patients were primary
refractory and the other 6 patients received the treatment for
relapsing disease. Five patients had received previously the HyperCVAD
regimen and 2 patients had undergone an autologous stem cell transplant.
At GEMOX-R treatment, 92% percent of the patients presented
an Ann Arbor stage III-IV, high LDH in 36% of patients, a higher than 1
ECOG performance status in 30% of patients and IPI>2 was present in
46%. Results. Sixty-seven percent of the patients achieved a CR and 17%
a PR for a total response rate of 84%. With a median follow up for alive
patients of 14 months, OS was 56% and PFS was 46% at 24 months. The
median survival was 14.3 months. At present 5 patients remain free of
progression. Two patients remain free of disease at 17 and 36 months
respectively. The major toxicity was thrombopenia grade III-IV present
in 31% of the patients. Neurotoxicity grade I-II was present in 46% of
patients. Factors related with overall survival were ECOG performance
status and a-IPI at GEMOX-R. Summary/Conclusions. These preliminary
observations in 13 patients suggest that GEMOX-R displays an outstanding
efficacy with an excellent toxicity profile in an elderly population
heavily treated with prior intense regimens for this disease. The high
response rate with a high CR rate suggests a striking synergism between
haematologica/the hematology journal | 2007; 92(s1) | 431