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

12 th Congress of the European Hematology Association
thy is an antibody-mediated demyelinating neuropathy caused by anti-
MAG monoclonal IgM or rarely IgG in the context of a monoclonal
gammopathy or lymphoproliferative disorder. The clinical picture is
characterized by a distal, symmetric and sensori-motor neuropathy associated
with a reduction or lack of deep reflexes and a decrease of superficial
and deep sensitivity. The diagnosis relies mainly on blood tests
demonstrating, by ELISA or Western blot, the Ig reactivity against MAG.
Anti-MAG neuropathy is frequently treatment-resistant and most of
the therapies currently used (high-dose IV immunoglobulins, chlorambucil,
INF-α and plasma exchange) cause toxicity or patient’s disconfort.
Since it has been demonstrated that the lowering of the MAG-antibody
titer correlates with an improvement in neuropathic symptoms,
the main task of treatment for anti-MAG neuropathy is to reduce the
antibodies concentration. Rituximab, a monoclonal anti-CD20 antibody
suppressing B cell clones, has been recently introduced in the treatment
of this neuropathy. Aims. The aim of this study was to review clinical
characters and therapy in a series of patients treated in our Institution
for anti-MAG neuropathy. The feasibility and effectiveness of rituximab
in patients resistant to first-line treatments was also evaluated. Patients
and Methods. Eleven patients (three women and eight men), with a median
age of 63 years (range 52-71) were included. Five patients were affected
by a monoclonal gammopathy of unknown significance (MGUS),
five by a low-grade B-cell non-Hodgkin lymphoma, one by AL amyloidosis
with MGUS. All patients received, at diagnosis and after each
treatment, a complete haematological staging including bone marrow
biopsy and molecular analysis of BCL-2/IgH or IgH VDJ rearrangements
when required. A neurological assessment was also conducted through
clinical evaluation and motor and sensory nerve conduction velocity
(MCV/SCV) test. Serum anti-MAG antibodies were determined by
ELISA or by Western Blot analysis. All patients received at least one previous
line of therapy and rituximab treatment was delivered in case of
absence of neurological clinical and instrumental response according to
the following schedule: 375 mg/mq I.V. for 4 weekly doses then repeated
every 3-6 months. Results. Patients characteristics and treatment are
summarized in the table. Among the eleven evaluable patients, only
two (n°3 and 4) had a clinical and instrumental improvement following
first-line treatments (chlorambucil + steroids and melphalan respectively)
while the remaining were resistant to more than one line of therapy.
Overall, seven patients of our series received rituximab because of a
worsening of the polineuropathy: two of them obtained a transient clinical
improvement, three a positive neurological response with a reduction
of monoclonal paraproteinemia and anti-MAG antibodies. Two
patients maintained a stable disease. No side effects were registered.
Conclusions. In our experience rituximab appears to be a safe and welltolerated
treatment for anti-MAG neuropathy, causing a positive, sometimes
transient, clinical response even in patients resistant to other therapies.
Since we observed better results in patients with a mild neurological
disability as compared to those with advanced disease, a prompt
introduction of rituximab should be considered in subjects resistant to
first-line treatment.
Table 1.
266 | haematologica/the hematology journal | 2007; 92(s1)
0714
THE FOLLICULAR LYMPHOMA INTERNATIONAL PROGNOSTIC INDEX IS APPLICAPLE IN
LYMPHOPLASMACYTIC LYMPHOMA / WALDENSTROMS MACROGLOBULINEMIA
G.A. Pangalis, T. Tzenou, M.C. Kyrtsonis, C. Kalpadakis,
T.P. Vassilakopoulos, S. Sachanas, Z. Galanis, S. Masouridis,
M.N. Dimopoulou, S.I. Kokoris, E.M. Dimitriadou, P. Korkolopoulou,
M.P. Siakantaris, M.A. Angelopoulou, P. Panayiotidis, G.A. Pangalis
University of Athens Medical School, ATHENS, Greece
Introduction. FLIPI is a simple and effective model for the evaluation of
prognosis in patients with follicular lymphoma. Recently, it has been
applied and validated in primary nodal marginal zone lymphoma (MZL)
and non-gastric MZL. Consequently, the assessment of its prognostic
significanse in other low grade B-cell lymphomas seems reasonable,
especially in LPL/WM, a disease presenting a degree of overlap with
MZL. Aims. To assess FLIPI score validity for prognosis in LPL/WM.
Patients and Methods. 122 patients were studied. Fourty-two (25 women,
17 men) presented LPL (not secreting IgM), their median age was 61
years, 7 were in Ann-Arbor stage I, 2 in II, 2 in III and 31 in stage IV. Lymphadenopathy
was present in 31 and splenomegaly in 6. Their median
follow-up was 96.9 months. Eighty patients presented WM, 31 women
and 49 men with a median age of 64 years. All patients were in Ann-
Arbor stage IV, by definition, due to bone marrow involvement, 15 presented
lymphadenopathy and 10 splenomegaly; their median follow up
was 139 months. FLIPI score at diagnosis was calculated in all patients
who were accordingly classified in three groups (low, intermediate and
high risk). Survival curves were plotted using the Kaplan-Meier method
and compared by the log-rank test. Results. In the LPL group, 13 patients
were classified as low risk, 16 as intermediate and 13 as high risk; median
survival was 65.1, 96.9 and 34.5 months respectively. The corresponding
5- and 10-year survival was 70% vs 94% vs 45% and 35% vs 47%
vs 17% in the low-, intermediate- and high-risk group respectively
(p=0.09). When low and intermediate risk group together were compared
to the high risk one, the corresponding 5- and 10-year survival was
84% vs 70% and 42% vs 35% (p=0.03). In the WM group, 7 were in the
low risk, 23 in the intermediate and 50 in the high risk group. Median
survival for these groups was 132.2 , 155.2 and 62.9 months respectively.
The corresponding 5- and 10- year survival was 100% vs 94% vs
54% and 100% vs 69% vs 29% in the low-, intermediate- and high-risk
group respectively (p=0.03). 5- and 10-year survival was 96% vs 54%
and 76% vs 29% (p=0.008), when the low and intermediate groups
were compared together to the high risk group. Conclusions. FLIPI seems
applicable in LPL/WM.
0715
THERAPEUTIC ROLE OF RITUXIMAB IN THE TREATMENT OF INTRAVASCULAR
LYMPHOMA
G.P. Dognini, 1 A. Szomor, 1 B. Horvath, 2 O. Bairey, 3 L. Uziel, 4
J.F. Seymour, 5 R. Willemze, 6 M. Ponzoni, 1 A.J.M. Ferreri1 1 San Raffaele Scientific Institute MILAN, Italy; 2 Semmelweis University,
BUDAPEST, Hungary; 3 Rabin Medical Center, Beilinson Hospital, PETAH
TIQWA, Israel; 4 Ospedale San Paolo, MILAN, Italy; 5 Australasian Leukaemia
& Lymphoma Group, MELBOURNE, Australia; 6 Dutch Cutaneous Lymphoma
Group, AMSTERDAM, Netherlands
Background. Intravascular lymphoma (IVL) is a rare form of non
Hodgkin lymphoma, characterized by the growth of large neoplastic
lymphocytes within the blood vessel. Diagnosis is often difficult and
outcome generally poor. The standard therapy remains to be defined,
but anthracycline-based chemotherapy is the most commonly used
treatment. A few recent case reports seem to suggest a further improvement
deriving from the addition of rituximab to chemotherapy. Aims. to
explore activity and efficacy of rituximab (375 mg/m 2 on day 1) plus
CHOP or CHOP-like chemotherapy (R-CT) in comparison to the same
chemotherapy alone (CT) in IVL patients selected from the largest series
collected in western countries. Methods. 25 IVL patients eligible for
anthracycline-containing regimen were evaluated. Clinical features and
outcome of 5 patients treated with R-CT strategy were compared to a
series of 20 patients treated with CT. Results. Median age of the 25
patients was 67 yrs (range 39-86 yrs). Twelve patients were males. The
most common involved sites were: skin (12 patients), CNS (7), bone
marrow (7), spleen (5), and liver (4). B symptoms were complained by
19 (76%) patients and an elevation of serum LDH was present in 20
(80%). Anaemia, leucopoenia and thrombocytopenia were observed in
8 (32%), 19 (76%), and 8 (32%) cases respectively. Eighteen (72%)