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

(range, 1-6) and 11 treatment cycles (range, 6-22). All patients were evaluated
for response and toxicities. The total objective response rate was
35.0% (1 CR, 6 PRs), and 55.6% in low-grade lymphoma, 18.2% in DLB-
CL. There was a trend of higher response in low-grade lymphoma than
DLBCL, but this difference was statistically insignificant (two sided Fisher’s
exact test, p=0.16). Adverse events were primarily hematologic toxicities;
the incidence of grade 4 neutropenia and thrombocytopenia was
each 25.0%. The treatment-related mortality was observed in one
patient, who had been previously treated with high-dose chemotherapy
plus TBI with autologous stem cell transplantation. Summary and conclusions.
RIT with I-131 rituximab seems to be effective and tolerable in
refractory low-grade B-cell NHL, although modest activity in refractory
DLBCL. Further studies to define the efficacy of I-131 rituximab in DLB-
CL are warranted, such as consolidation RIT followed by standard
chemotherapy or high-dose RIT with autologous stem cell transplantation.
0301
RITUXIMAB AND CHLORAMBUCIL AS FIRST LINE TREATMENT OF LOW-GRADE OCULAR
ADNEXAL LYMPHOMAS
L. Nassi, 1 L. Rigacci, 1 M. Puccioni, 1 E. Polito, 2 S. Mappa, 1 S. Dal Pozzo, 1
R. Alterini, 1 V. Carrai, 1 B. Puccini, 1 A. Bosi1 1 Careggi Hospital, FL; 2 Policlinico Le Scotte, SIENA, Italy
Background. Ocular adnexal lymphomas (OALs) represents 5-15% of
primary extranodal lymphomas, and are constituted largely by extranodal
marginal zone lymphomas (EMZL). Radiotherapy is associated to
high rates of local disease control, but also to the risk of relapse and
immediate and delayed complications, such as xerophtalmy, corneal
ulcerations, cataract and retinal damage. Surgery is a feasible option, but
not always satisfactory in terms of disease control. Single-agent
chemotherapy with alkylating agents is used for the treatment of lowgrade
lymphomas, including OALs. Rituximab, a chimeric anti-CD20
monoclonal antibody, is effective in EMZL and in OALs. Aims. We investigated
the efficacy and the safety of a combination of chlorambucil and
rituximab as first line treatment in patients with OALs. Methods. Patients
with histologically proven low-grade OALs were enrolled in this study.
Staging included CT-scan of the orbit, neck, chest and abdomen, MR of
the orbit, and bone marrow biopsy, and was done according to Ann
Arbor classification. Treatment consisted of chlorambucil (0,1 mg/Kg/die
for 45 days, then on days 1 to 15 monthly for 4 months) and rituximab
(375 mg/sqm weekly for 4 doses, then monthly for 4 infusions). Toxicities
were reported according to WHO criteria. At the end of treatment
patients were restaged clinically and with a MR of the orbit. Results.
Since November 2003 to December 2005 nine consecutive histologically
proven low-grade OALs (eight EMZL, a grade I follicular lymphoma)
have been treated according to this protocol. The median interval
between onset of the first symptoms and diagnosis was 13 months
(range, 4 months - 3 years). Six patients were female (66%). Median age
at diagnosis was 78 years (range, 56-86 years). Disease was localized in
the conjunctiva in four patients, in the lacrimal glands in 3 patients and
in other orbital sites in the last two patients. Eight patients had a stage
I disease, one stage IV, and no patient presented B-symptoms. LDH was
within normal range in all patients, ECOG-PS was 0 in all patients. All
patients completed the treatment without delay; there was no grade III-
IV toxicities nor hospitalizations. Five patients had grade 1-2 rituximab
infusion-related reactions usually during the first infusion. We did not
observe infectious complications. Haematological toxicity was mild. At
the end of treatment local symptoms were not present: eight patients
(89%) were in CR, and the remaining patient (11%) obtained a PR. After
a median follow-up of 22 months (range, 10-38 months) all patients are
alive and we did not observe disease progressions; the median EFS was
19 months (range, 8-36 months). All patients underwent periodic ophthalmologic
follow-up visits: we did not report ocular toxicities, and all
patients conserved a normal visual function, including acuity. Conclusions.
The combination of rituximab and chlorambucil proved to be a
safe, feasible and effective therapy for primary OALs. However, a longer
follow-up would be necessary to determine the long-term efficacy of this
treatment.
12 th Congress of the European Hematology Association
0302
PHASE I STUDY OF SMILE CHEMOTHERAPY FOR ADVANCED-STAGE OR
RELAPSED/REFRACTORY EXTRANODAL NK/T-CELL LYMPHOMA/LEUKEMIA
Y.L. Kwong, 1 M. Yamaguchi, 2 R. Suzuki, 3 W.S. Kim, 4 Y. Hasegawa, 5
K. Izutsu, 6 J. Suzumiya, 7 T. Okamura, 8 S. Nakamura, 3 K. Kawa, 9
K. Oshimi10 1 University of Hong Kong, HONG KONG, China; 2 Mie University, TSU,
Japan; 3 Nagoya University, NAGOYA, Japan; 4 Samsung Medical Center,
SEOUL, South-Korea; 5 Tsukuba University Hospital, TSUKUBA, Japan; 6 University
of Tokyo, TOKYO, Japan; 7 Fukuoka University, FUKUOKA, Japan;
8 University of the Ryukyus, NISHIHARA, Japan; 9 Osaka Medical Center,
OSAKA, Japan; 10 Juntendo University, TOKYO, Japan;
Background. Extranodal NK/T-cell lymphoma, nasal type, and aggressive
NK-cell leukemia are rare, and their standard therapy has not been established.
They are Epstein-Barr virus (EBV)-associated lymphoid malignancies,
and lymphoma/leukemia cells express P-glycoprotein leading to multi-drug
resistance (MDR) of the disease. Almost all patients with stage IV,
relapsed, and refractory diseases die within 1 year. Aims. To establish a
more effective induction therapy for these neoplasms with untreated stage
IV or relapsed/refractory state, we conducted a dose escalating feasibility
study of a newly designed chemotherapeutic regimen, SMILE
[Steroid=dexamethasone (DMS) 40 mg/body d2-4 IV, Methotrexate
(MTX) 2 g/m 2 d1 6hr IV, Ifosfamide (IFM) 1.5 g/m 2 d2-4 IV, L-asparaginase
(L-asp) 6000U/m 2 d8,10,12,14,16,18,20 IV, and Etoposide (ETP) 100 mg/m 2
d2-4 IV; every 28 days]. SMILE comprised MDR-unrelated agents and
ETP that shows both in vitro and in vivo efficacy for EBV-associated lymphoproliferative
disorders. Methods. Primary endpoint is MTD (maximum
tolerated dose), and secondary endpoints are the overall response rate
(ORR) and the complete response (CR) rate. Pts with newly diagnosed
stage IV diseases (including aggressive NK-cell leukemia), first relapsed/
recurrent diseases after CR/PR, refractory (either NC or PD) diseases with
first-line chemotherapy, 15-69 years of age, and PS 0-2 were eligible. A
standard 3+3 design was used to evaluate dose-limiting toxicities (DLTs).
The doses of DMS, IFM, and L-asp were fixed. Four dose levels of
MTX/ETP were planned to be evaluated. Results. At Level 1, 6 pts with
extranodal NK/T-cell lymphoma, nasal type were enrolled, and showed
the following features; age 28-69 yrs (median 48), M:F=5:1, newly-diagnosed
stage IV: 3, 1st relapse: 2, primary refractory: 1, BM involvement:
2, elevated serum LDH: 4, and PS0: 2 , PS1: 3, PS2: 1. Among the first 3
pts, 1 pt died from sepsis with grade 4 neutropenia due to disease and
delayed initiation of G-CSF administration. 1 pt developed grade 3 infection
and hypofibrinogenemia. The remaining 1 pt did not develop DLT
other than transient grade 3 hyponatremia, and obtained a CR. We made
a protocol amendment to initiate G-CSF administration from day 6, and
proposed to register additional 3 pts in Level 1. It was approved by the
Data and Safety Monitoring Committee. Additional 3 pts developed DLTs
(grade 3 APTT 1, grade 3 gamma-GTP 1, grade 3 hyponatremia 2, and
grade 3 hyperglycemia 1) that were all manageable, and pts recovered
from the toxicities rapidly. The incidence of grade 4 neutropenia was
comparable, but grade 3/4 leukopenia/ anemia/ thrombocytopenia were
less frequent than the first 3 pts. Of all 6 enrolled pts, 3 achieved CR, 1
PR, 1 NR, and 1 NE.%ORR was 67%, and%CR was 50%. Summary and
Conclusions. Our results suggest that dose level 1 of SMILE is feasible and
promising for advanced, refractory or relapsed NK/T-cell lymphoma. To
determine the efficacy and feasibility of SMILE in a large number of cases,
we will start the subsequent phase II study of SMILE in spring 2007.
0303
RITUXIMAB MAINTENANCE THERAPY FOR PATIENTS WITH FOLLICULAR LYMPHOMA. A
COST-EFFECTIVE STRATEGY?
C. Francisco J., 1 E. Conde, 2 P. Giraldo, 3 J. Gomez Codina, 4
M. Provencio, 5 E. Rios, 6 A. Rueda, 7 C. Rubio-Terres, 8 C. Varela9 1 Hospital Universitario Puerta del Mar, CADIZ; 2 Hospital U. Marqués de
Valdecilla, SANTANDER; 3 Hospital Universitario Miguel Servet,
ZARAGOZA; 4 Hospital Universitario La Fe, VALENCIA; 5 Hospital Universitario
Puerta de Hierro, MADRID; 6 Hospital Virgen del Rocío, SEVILLA; 7 Hospital
Virgen de la Victoria, MALAGA; 8 HEALTH VALUE, MADRID; 9 Roche
Farma, MADRID, Spain;
Background. Rituximab, a chimeric anti-CD20 monoclonal antibody, has
shown to significantly improve overall survival (OS) (p=0.011) and progression
free survival (PFS) (p