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

1295
HEMOPHAGOCYTIC LYMPHOHYSTIOCYTOSIS PRESENTED AS A COMPONENT
OF MULTIPLE ORGAN DYSFUNCTION SYNDROME IN PEDIATRIC INTENSIVE CARE UNIT
D. Yilmaz, B. Karapinar, C. Balkan, Y. Aydinok, S. Can, B. Erer,
K. Kavakli
Ege University Faculty of Medicine, IZMIR, Turkey
Background. In Pediatric Intensive Care Unit (PICU) multiple organ dysfunction
syndrome(MODS) is a frequent diagnosis. Most of the patients
with MODS are secondary to sepsis. Hemophagocytic lymphohystiocytosis
is a rare disorder which can cause a sepsis like syndrom with multiple
organ dysfunction. Aims. Here we describe 7 children presented with
HLH and MODS to PICU of a tertiary care center to notice that HLH can
be presented as a component of MODS. Unless the diagnosis of HLH is
considered and appropriate treatment started it can be fatal. Methods. All
patients records who admitted to PICU of Ege University Hospital
between December 20005 and February 2007 were reviewed. The records
of the patients presented with MODS and HLH at the admittion to PICU
were evaluated retrospectively. Results. Seven children (female/male= 4/3)
were admitted to PICU of Ege University Hospital because of prolonged
fever of unknown origin, pancytopenia and MODS between December
2005 and February 2007. The median age at the admittion was 13 months
(range 3 months -15 years). Five of the patients had 6 organ dysfunction,
one had 5 and the other had 3. The lowest PELOD score was 12 and the
highest was 62 with a median of 51. All of the patients met the diagnostic
criteria of Hemophagocytic lymphohystiocytosis (HLH) and in all
patients Bone marrow aspiration revealed hemophagocytosis without
malignancy. All the patients required mechanical ventilation, 6 out of 7
were supported by inotropic±vasopressor agents. Neurologic system
involvement was seen in 6 patients and all had a Glascow Coma Score
below 7, and two had seizure at the admittion to PICU. Severe clinical
hemorrhage was seen in all patients at the presentation. Of the 7 children,
4 (%57.1) died. Two of these children expired just after they were admitted
to PICU. They had the highest PELOD scores in this small series (62
and 61). Other 2 patients expired during the first days of HLH- 2004 treatment
protocol. Among the patients survived, one with brucellosis was
given only anti Brucella treatment and IVIG. His clinical and laboratory
findings resolved rapidly. This patient had the lowest PELOD score at the
time of diagnosis. Other two patients were put on HLH- 2004 protocol
and they are still in remission. Conclusions. HLH is a rare disorder with a
high mortality rate. HLH can share the same pathophysiologic elements
with MODS and severe sepsis, septic shock. Clinician should be aware
of the diagnostic criteria of HLH. In the presence of prolonged fever and
pancytopenia in PICU patients who presented with MODS the diagnosis
of HLH should be recognized.
1296
CLINICAL EFFECTS OF 5-AZACITIDINE FIVE DAYS/MONTHLY SCHEDULE IN THREE
SYMPTOMATIC LOW-RISK (IPSS: 0-1) MYELODISPLASTIC PATIENTS
C Fili’, C. Bergonzi, C. Skert, M. Malagola, A.M. Roccaro, A. Peli,
E. Capuzzi, D. Russo
Chair of Hematology, Brescia, BRESCIA, Italy
Promising results have been reported by the use of nucleoside 5-azacitidine
(5-Aza) in the treatment of myelodysplastic syndrome (MDS).
When 5-Aza was administered at a dose of 75mg/mq/day subcutaneously
for 7 days, every 28 days, it showed to be superior to supportive care,
with higher response rates and reduced risk of progression to acute
myeloid leukaemia (AML), mainly in the high risk MDS patients. We
attempted to use an alternative schedule, 75 mg/mq subcutaneous daily
for 5 consecutive days every 28 days, to evaluate its efficacy and tolerability
in low risk MDS patients. Between May and December 2006 we
treated five patients affected by refractory anemia (RA) with Low Risk
IPSS (score 0-1). Age at diagnosis ranged between 66 and 73 years. All
patients failed EPO therapy and were in chronic red blood cell (RBC) supportive
care with a median transfusions requirement of 4 units/monthly.
The 5-Aza five days/monthly schedule was administered for a total of 8
courses. The response treatment criteria was according to International
Working Group (IWG) as reported by Cheson et al. Two months after the
end of therapy (8 courses) the evaluation of response was completed in
3 out of 5 patients. An hematologic improvement (HI) was observed in
two patients, both reaching a major erythroid response (major HI-E), with
no longer needed transfusions and RBC transfusion independence of 20
and 16 weeks respectively. The third patient obtained a transitory major
HI-E after the 2th course of treatment, maintaining a transfusion independent
time for 16 weeks and increasing haemoglobin greater than 2
12 th Congress of the European Hematology Association
g/dL; he failed after the 7th course of therapy. Quality of life (QOL) measured
by the FACT-An score improved in all patients. Extrahematologic
toxicity was mild and consisted in nausea and vomiting (WHO grade I)
in two patients and flu-like syndrome with fever (WHO grade I) in one
patient. Hematologic toxicity consisted in neutropenia (WHO grade III)
and thrombocytopenia (WHO grade II) in one patient; it was transitory
and no delay of treatment was necessary. Our preliminary results show
that the 5-Aza five days/monthly schedule is very well tolerated and it
appears to have an efficacy similar to the seven days/monthly schedule,
at least in low-risk MDS setting. Considering that the optimal schedule
and duration for demethylating agents has not yet been established, further
MDS patients recruitment is warranted to confirm the efficacy of this
alternative 5-Aza low dose regimen.
1297
APOPTOTIC CHARACTERISTICS OF MESENCHYMAL STROMAL CELLS FROM BONE
MARROW OF CHILDREN
H. Dimitriou, C. Perdikogianni, G. Martimianaki, I. Pelagiadis,
E. Stiakaki, M. Kalmanti
University of Crete, HERAKLION, CRETE, Greece
Background. Mesenchymal stromal cells (MSC) represent a novel promising
field in transplantation. Their relatively easy and quite effective in
vitro expansion makes them even more attractive. The aim of the study
was to assess the effect of pro apoptotic conditions and that of long - term
expansion through serial passages on the characteristics of MSC from
children. Material-Methods. Sixteen bone marrow (BM) mononuclear cell
cultures from children with benign hematological disorders (n=10) and
solid tumours without BM involvement (n= 6) have been initiated and
were assessed for 10 passages. The expression of CD105, CD146 and
CD95 as well as apoptosis by 7AAD staining, were evaluated by flow
cytometry. In every passage CFU-F assay was performed and the cell
doubling time was calculated. Cell cycle characteristics were assessed
by propidium iodide staining at P2 and P6. Results. CFU-F counts ranged
from 40.71+4.3 in P1, to 15.5 + 6.7 in P10. The cell doubling time was
found to be 2.01±0.14 days at P1, increasing to 3.5±1.19 days at P8. A low
percentage of apoptotic and dead cells was detected by 7AAD staining
at P2 (3.0±0.6%) and this did not change until P10. In order to test if
CD95 is functional, induction of apoptosis was triggered by the addition
of different concentrations of an agonistic antibody (20ng and 1
microg/mL, anti-Fas CH-11) under standard culture conditions. A minor
effect on MSC survival was observed at the highest anti-Fas concentration
used. Additionally, serum deprivation of MSC for up to 72 hours
revealed no substantial apoptotic effect. According to the cell cycle analysis,
cells at P2 are mostly at GoG1 phase (72.9 + 8.4%, S phase: 19.6 +
7.4%) while at P6 there is a slight increase in the cells that have entered
cell cycle (GoG1 64.5+7.5% and S 24.4 + 5.8%). Conclusions. It seems that
MSC from children with benign hematological diseases and solid tumors
without BM involvement, retain their functional characteristics throughout
serial passages and are very stable under conditions that usually cause
apoptosis although progression in passages results in a lower number of
cells maintaining quiescence. This could be very useful in the setting of
transplantation as long as serum deprivation for up to 72 hours does not
seem to affect in vitro expanded MSC, while, in the clinical setting, avoiding
the use of serum protects from the possible risk of immune responses
attributable to serum contamination. These features make MSC, especially
those of early passages, optimal candidates for use in transplantation
and cellular therapy.
1298
EPIDOMIOLOGIE STUDY OF ACUTE LEUKEMIA IN TUNISIA (MULTICENTRIC NATIONAL
STUDY)
M. Elloumi, R. Jeddi, M. Laatiri, L. Aissaoui, H. Bouaziz, A. Khelif,
B. Meddeb, T. Souissi
Hematology, SFAX, Tunisia
This is a retrospective multicentric national study, in which we present
epidemiologic data concerning Acute Leukemia cases followed up in
all haematology departments in Tunisia during a ten year period (1995-
2004). 1801 acute leukaemia cases are recorded : 1037 acute myeloid
leukaemia (AML) (57,6%), 752 (41,8%) acute lymphoblastic leukaemia
le (ALL), 5(0,3%) biphenotypic and 7 (0,4%) undifferentiated. The
national incidence is 1,9 cases per 100 000 habitants per year ; i.e 1,1 for
AML and 0,8 for ALL. The incidences in the differents gouvernorats (districts)
vary from 1 per 100 000 inhabitants per year in Kebily (south) to
2,66 in Beja (north), the difference being statistically significant ( p<
haematologica/the hematology journal | 2007; 92(s1) | 469