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

12 th Congress of the European Hematology Association
0182
EXPRESSION OF ANGIOGENESIS RELATED FACTORS IN HODGKIN'S LYMPHOMA
F.H. Passam, 1 M. Kafousi, 2 M. Foteinou, 1 G. Tsirakis, 3 P. Roussou, 1
D.S. Kyriakou, 4 M.G Alexandrakis, 3 E. Stathopoulos 2
1 Sotiria Hospital, ATHENS; 2 Dept of Pathology, Medical School Crete, HER-
AKLION, 3 Dept of Hematology, Medical School Crete, HERAKLION; 4 University
Hospital of Larisa, LARISA, Greece
Background. Angiogenesis is a prerequisite for solid tumour growth
and dissemination but there is relatively few data related to its significance
in Hodgkin lymphoma. Aims. The purpose of the study was to
examine the immunohistochemical expression and distribution of angiogenic
and proliferation markers in Hodgkin biopsies and their relationship
to clinical parameters. Materials and Methods. Slides from paraffin
embedded lymph nodes from 62 patients with Hodgkin lymphoma
were obtained from the Pathology Departments of two tertiary hospitals.
Immunohistochemical staining was performed on tissues after
dewaxing and rehydration with Vascular Endothelial Growth Factor
(VEGF) (Santa Cruz), Hypoxia Inducible Factor 1 α (HIF1a) (Santa Cruz),
Platelet Derived Growth Factor Receptor alpha (PDGFRa) and MIB-1
(Neomarker). Alkaline phosphatase polymer was used for detection of
all antibodies. CD31 staining was performed and the microvessel density
(MVD) was defined by identifying three hot spots at 100X magnification
and counting at 400X with a graded graticule corresponding to
a 0,0625 mm 2 surface area. Appropriate negative and positive controls
were used. In all cases neoplastic cells, reactive background cells and
endothelial cells were evaluated. A case had a score of 0 when less than
10% of neoplastic cells reacted with the antibody, 1 for staining of 10-
30% of cells, 2 for 30-50% and 3 when more than >50% of cells were
stained. Results. Immunohistochemistry showed that VEGF was negative
in the neoplastic population in 53% of cases whereas 30% of cases
showed strong staining (score 3). The reactive population in the
lymph node biopsy was positive in over 50% of cases. HIF1a was positive
in the neoplastic compartment in 31% of cases whereas PDGFRa
in 95% of cases. MIB-1 was positive in 70% of cases and in the range
of 20-50% of Reed Stenberg and alike cells. The MVD had a median of
2.6 which was not different from reactive lymph nodes. VEGF in the
non-neoplastic compartment correlated significantly with Ann Arbor
stage with increased staining in I-II versus stages III and IV (spearman
rho: -0.329, p:0.017). Also higher VEGF score in reactive cells correlated
with increased incidence of complete response (p:0.03). Increased MVD
was associated with the presence of necrotic lesions in the material
(p:0.05). Conclusion. Microvessel formation is not increased in Hodgkin
in comparison to reactive lymph nodes although there is expression of
angiogenic molecules by neoplastic and surrounding cells. VEGF shows
a higher level of expression in earlier stages of disease.
66 | haematologica/the hematology journal | 2007; 92(s1)
0183
EARLY INTERIM FDG-PET SCAN IN LOCALISED HODGKIN LYMPHOMA: EVALUATION IN 5
FRENCH CENTERS
M.S. Dilhuydy, 1 P. Brice, 2 T. Traulé, 3 P. Solal-Celigny, 4 S. Hirt, 5
A. Pariente, 6 O. Fitoussi5 1CHU de Bordeaux, PESSAC CEDEX; 2Hopital Saint Louis, PARIS; 3Hospices Civils de Lyon, LYON; 4Centre Jean-Bernard, LE MANS; 5Polyclinique Bordeaux
Nord, BORDEAUX; 6Département de Pharmacologie, BORDEAUX,
FranceBackground.
Long-term survival from Hodgkin lymphoma (HL) in early-stage (I-II)
patients is more than 85%. However, certain patients have a primary
refractory disease with a worse evolution. Early interim FDG-PET scan
performed after 2 courses of chemotherapy (PET-2) provides an early and
accurate assessment of response and a correlation has been demonstrated
between normalization of PET-2 and patient outcome. Aims. To evaluate
the percentage of negative PET-2 in early-stage patients, and to
seek clinical or biological factors predictive of positive PET-2. Methods.
Forty-seven patients from five French centers with early-stage Hodgkin
lymphoma received ABVD as first-line chemotherapy. PET-2 was performed
3 weeks after the second course of ABVD. Radiotherapy and
changes in management according to FDG-PET scan result could be
decided by the clinician. Evaluation was retrospective. Results. The median
age was 33 years (range17-72). Thirty patients were male. Seventy
percent of patients were in unfavorable group according to EORTC criteria
(one or more of the following criteria: age > 50, systemic symptoms,
elevated ESR >50 mm, bulk disease and more than three lymph
node areas involved). Thirty-nine patients had a pre-treatment FDG-
PET scan with a modification of staging in 6 cases. Initial staging according
to CT scan or FDG-PET scan was as follows: IA: 5 patients, IB: no
patient, IIA: 26 patients and IIB: 16 patients. Thirty nine patients (83%)
had a negative PET-2 and 2 had minimal residual uptake whereas 6
patients (13%) had a clearly positive PET-2. Among the 39 patients with
negative PET-2, 31 patients undergo radiation therapy after completion
of four courses of ABVD. Among the 6 patients with positive PET-2,
treatment intensification (BEACOPP) occurred for 3 patients with a negative
FDG-PET scan after two courses. For patients having ABVD, FDG-
PET scan results after four cycles were as follows: one remained with
minimal disease, one had a negative FDG-PET scan and one had a positive
FDG-PET scan. At a median follow-up of nine months, one patient
with negative PET-2 relapsed early after the end of chemotherapy. The
46 other patients are in failure-free survival. Unfortunately, no clinical
or biological factor (from EORTC criteria) was significantly predictive
for PET-2 result. Conclusions. We showed in this series that negative PET-
2 is obtained in 83% of patients with early stage disease. These results
are similar to those expected in the EORTC H10 trial which evaluates
PET-2 guided treatment adaptation and expect about 85-90% of negative
PET-2. No clinical or biological factor was significantly predictive for
PET-2 result. Prospective studies, like H10 EORTC trial are warranted
to confirm these results and find predictive factors for a positive PET-2.