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

12 th Congress of the European Hematology Association
patients with unmutated VH genes had higher median lymphocyte
counts (p=0.001), higher total tumor mass score (p=0.001) and more
often presented at an advance clinical stage (p=0.005) compared to
patients utilizing mutated VH genes. Treatment was initiated for symptomatic
or progressive disease CLL cases. Patients with early stage and
stable disease were not treated. First line therapy consisted of Chlorambucil
in 73 patients (67.59) and Fludarabine in 16 patients (14.81%). Early
stage unmutaed cases had very short median time to progression (11
months). Also, unmutated cases had worse response to treatment
(p=0.005) compared with mutated CLL patients, regardless of the treatment.
Moreover, the median survival of patients with unmutated VH
genes was considerably shorter (VH unmutated, 56 months, VH mutated,
125 months; p< 0.001). Summary/Conclusions. Our data confirmed
the prognostic value of immunoglobulin VH genes mutational status in
CLL, which divides the disease in two prognostic subsets in terms of
overall survival and clinical characteristics of the disease. Results from
the treatment of unmutated cases indicate that they could have increased
treatment benefit if they are treated earlier with more intensive first line
therapy. We consider that analysis of the mutational status of the
immunoglobulin VH genes may allow for an individualized approach to
CLL treatment in the near future and we suggest clinical trials of more
effective treatment stratified by this single prognostic marker to be
designed.
1411
CLINICAL ASSESSMENT OF THE SENSITIVITY OF LEUKEMIC CELLS TO CHEMOTHERAPY
IN PROGNOSIS OF 7 YEARS DFS SURVIVAL IN CHILDHOOD ALL
T. Astrelina
Research Institute of Pediatric Hematol, MOSCOW, Russian Federation
Background. The determining in vitro drug resistance may reveal clinically
relevant information for prognosis the efficacy of chemotherapy in
childhood leukemia. Aims. of this study was to evaluate the correlation
between blast cells sensitivity profile to chemotherapy ex vivo (according
to range scale) and the probabilities of 7-year disease-free survival.
Methods. The blast cells sensitivity to chemotherapy (10 drugs) was
examined in MTT-assay. The material of the study-bone marrow from
169 children with newly diagnosed ALL. Results. For each drug (Prednisolone,
Dexamethasone, Vincristine, L-Asparaginase - PDVA) LC50
was determined. The degree of cytotoxity was estimated in ranks scale:
each step of a drug dilution (from greatest to lowest) was corresponded
to rank (from 1 up to 7). The high sensitivity to a drug - LC50 value from
1 to 4 ranks; low sensitivity - LC50 value from 5 to 7 ranks. The present
data on analyze correlations between these potential prognostic factors
and well-known favourable and unfavourable markers of prognostic
in ALL. The probability of 7-year disease-free survival was significantly
higher in patients with high sensitivity (1-4 ranks) to Prednisolone
(p=0.036), Dexamethasone (p=0.043), Vincristine (p=0.041), L-Asparaginase
(p=0.042), in comparison with the patients with low sensitivity (5-
7 ranks). The probability of 7-year disease-free survival in patients with
high simultaneous sensitivity to 3 of 4 drugs (PDVA) was 0.88 versus
0.62 in patients with low simultaneous sensitivity to three of these drugs
(p=0.037). Conclusions. the initial sensitivity of leukemic cells to Prednisolone,
Dexamethasone, Vincristine, and L-Asparaginase is very significant
in prognosis of 7 - years disease-free survival in pediatric ALL.
High simultaneous sensitivity to at least 3 of 4 above mentioned drugs
appears to be good prognostic factor.
1412
DONOR TRANSMITTED LYMPHOMA MALIGNUM IN A KIDNEY-TRANSPLANT RECIPIENT
M. Kowal, 1 M. Hus, 1 J. Kocki, 2 M. Majewski, 3 K. Giannopoulos, 1
A. Dmoszynska1 1 Medical University Lublin, LUBLIN; 2 Dept of Medical Genetics Medical
Univers, LUBLIN; 3 Molecular Biology Lab Inst Hemat and Tra, WARSOW,
Poland
Introduction. Transmission of cancer from organ donors is considered
as a fatal risk following solid organ transplantation. The Danish Cancer
Registry (2002) quantified the risk in a population-risk register of 1.3%
for having a donor with an undetected malignancy and 0.2% risk of
getting a transmitted cancer. In the most recent commentary from the
UNOS/OPTN a cancer transmission rate of 0.018% was identified utilizing
a cadaveric donor source (2005). To the best of our knowledge, no
example exists of a acute lymphoblastic leukemia (ALL) T-cell accidentally
transplanted to recipient of renal from donor with the malignant
lymphoma, lymphoblastic T-cell. Case report. A 19-year old donor suf-
506 | haematologica/the hematology journal | 2007; 92(s1)
fered from deep cerebral anoxia due to a choked with tablet, without
any history of malignant. His family consented for multiorgan transplantation.
On June 2005, at the time of organ retrieval no abnormalities
were detected. After transplantation autopsy was performed, this
demonstrated the limited infiltration of the mediastinal tumor arising in
thymus. The diagnosis of lymphoma type lymphoblastic of T cell origin
was made. A recipient of first kidney, 59 year old woman with a history
of end stage renal disease secondary to glomerulonephritis, having
been informed of the donor autopsy findings, decided to retain her allograft.
Immunosupresion consisted of tacrolimus, mycophenolate mofetil
and prednisolone. At the first, third and 5-month assessments she was
asymptomatic and renal function remained good. Ultrasound scans of
the graft were reported as normal. On december 2005, 6 month after
transplantation she developed general malaise. It was noted a mild
leukopenia and thrombocytopenia. A bone marrow specimen revealed
massive infiltration of lymphoblasts. The immunophenotyping analysis
showed the same antigenic profile and immunoglobulin monotypic
restriction of the abnormal T cells, both in the thymus of the donor and
the bone marrow of the recipient. FISH studies for sex chromosomes
were performed to evaluate the origin of the blastic cells. The gene
rearrangement studies confirmed the clonal origin of the blasts in the
recipient. These findings lead us to speculate that the clonal origin of the
tumor was the same in the both donor and recipient. At nearly the same
time after transplantation, the identical type of tumor were observed in
the other centers, in the second renal and liver recipients with grafts
from same cadaveric donor (data unpublished). It is probable that lesions
in the grafts were metastases that developed in the recipients over several
months. This malignant clone was more aggressive and became at
a disseminated stage, partly due to the effects of immunosupression. In
conclusion, organs transplant recipiens shouls be carefully followed up
for malignancy, despite the absolute risk of cancer transmission with solid
organ transplantation is low but real.
1413
ACTIVATION OF AKT PREDICTS POOR OUTCOME IN NEUROBLASTOMA
S. Fulda, 1 D. Opel, 1 C. Poremba, 2 T. Simon, 3 K.M. Debatin, 1
S. Fulda1 1 University Children's Hospital, ULM; 2 University of Duesseldorf, DUESSEL-
DORF; 3 University of Cologne, COLOGNE, Germany
While aberrant activation of the PI3K/Akt pathway, a key survival
cascade, has previously been linked to poor prognosis in several human
malignancies, its prognostic impact in neuroblastoma has not yet been
explored. We therefore investigated the phosphorylation status of Akt,
S6 ribosomal protein as target of mTOR and ERK in 116 primary neuroblastoma
samples by tissue microarray and its correlation with established
prognostic markers and survival outcome. Here, we provide for
the first time evidence that phosphorylation of Akt at serine 473 (S473)
and/or threonine 308 (T308), S6 ribosomal protein and ERK frequently
occurs in primary neuroblastoma. Importantly, we identified Akt activation
as a novel prognostic indicator of decreased event-free or overall
survival in neuroblastoma, whereas phosphorylation of S6 ribosomal
protein or ERK had no prognostic impact. Also, Akt activation correlated
with parameters of aggressive disease, including MYCN amplification,
1p36 aberrations, advanced disease stage, age at diagnosis and
unfavorable histology. Monitoring Akt at T308 or both phosphorylation
sites improved the prognostic significance of Akt activation in neuroblastoma
specimens compared to S473 phosphorylation. Parallel experiments
in neuroblastoma cell lines revealed that activation of Akt by IGF-
1 significantly inhibited TRAIL- or chemotherapy-induced apoptosis in
a PI3K-dependent manner, since the PI3K inhibitor LY294002 completely
reversed the IGF-1-mediated protection of neuroblastoma cells from
apoptosis. By demonstrating that activation of Akt correlates with poor
prognosis in primary neuroblastoma in vivo and with apoptosis resistance
in vitro, our findings indicate that Akt presents a clinically relevant target
in neuroblastoma that warrants further investigation.
1414
SPONTANEOUS SPINAL EPIDURAL HEMATOMA IN POLYCYTHEMIA VERA.
REPORT OF A CASE
N. Fernandez Mosteirin, C. Salvador Osuna, N. Padron, A. Godoy,
B. Soria, F. Sevil, P. Mayayo, M. Torres, P. Delgado, J.F. Lucia, M. Giralt
Hospital Universitario Miguel Servet, ZARAGOZA, Spain
Background. Bleeding manifestations in polycythemia vera (PV) are
commonly observed during therapy of anticoagulants or antiplatelet