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

0994
INCIDENCE OF INVASIVE ASPERGILLOSIS (IA) IN A TERTIARY HEMATOLOGICAL CENTRE
IN CZECH REPUBLIC, EVALUATION OF THE GALACTOMANNAN MONITORING
M. Kouba, 1 P. Cetkovsk˘, 1 J. Cermák, 1 J. Maaloufová, 1 M. Marková, 1
D. Pohlreich, 1 G. Smelá, 2 P. Soukup, 1 V . Válková, 1 A. Vítek 1
1 Institute of Hematology and Blood Transf, PRAGUE, Czech Republic; 2 The
General Teaching Hospital, PRAGUE 2, Czech Republic
Background. IA is a major opportunistic infection in patients with hematological
malignancies. The incidence of IA has increased in the past years.
The high mortality due to IA reflects both the invasivity of the pathogen
and the profound immunosuppression of the host organism. Aims. We retrospectively
evaluated the monitoring of galactomannan (GM) - twice a
week sampling using a commercial kit (one-stage immunoenzymatic
sandwich microplate assay) in a tertiary hematological centre. The aim
was to assess the burden of IA and to evaluate the benefit of GM monitoring.
Methods. In the study period (5/2005-12/2006) 330 patients at risk
of IA (407 patients were hospitalized in the same period in total) were
repetitively sampled for GM. Median number of samples per patient was
12. The spectrum of underlying diseases for the 330 sampled patients
was: 33% AML, 19% MDS, 21% lymphoproliferative diseases and multiple
myeloma, 14% myeloproliferative diseases, 6% high dose corticosteroid
treatment, 7% others. The same population of 330 patients divided
according transplant status: 35% after allogeneic stem cell transplant
(SCT), 3% after autologous SCT and 62% nontransplanted. For the IA
case-definition we used the EORTC/MSG criteria, but as clinically relevant
we considered only the proven and probable categories. We omitted
the possible EORTC/MSG category from our analysis. For the defining
positivity of GM we used the dynamic cut-off (index > 0,5 in two samples)
for serum samples and static cut-off (index > 0,5 in a single sample)
for bronchoalvelar lavage (BAL) samples. Results. None of the GM nonmonitored
patients developed IA in our centre in the study period and
there was no autopsy or biopsy proven case of IA in the study period in
the GM monitored group, which would escape early diagnosis. 23
patients in the sampled group (n=330, all hospitalized) fulfilled the criteria
of proven (2 cases) or probable IA (21 cases). Of the 23 proven and
probable cases: 15 patients were treated for hematological malignancies
- nontransplanted, 7 patients were after allogeneic SCT and 1 suffered
from severe aplastic anemia. As a microbiological criterion for diagnosis
served in 19 cases positive serum GM, in 2 cases positivity of GM from
BAL, in 1 case cultivation from blood culture and concomitantly positive
serum GM and in 1 case positive histology of pulmonary tissue and concomitantly
positive serum GM. Only two of the 23 patients diagnosed
to have IA are alive on follow-up (at 2/2007). The incidence of IA among
hospitalized patients in our centre was in the study period 5,7% (23/407).
The overall mortality (both IA related and IA non related) in patients
with diagnosed IA reached 91% on follow up. Summary. We conclude
that the incidence of 5,7% in our cohort is in concordance with published
numbers for its the risk profile. GM is of considerable help in the
diagnosis of IA (although we could not validate its performance in terms
of sensitivity and specificity). The mortality in patients with IA is very
high on follow-up.
0995
THE SIZE OF THE ACTIVE HEMATOPOIETIC STEM CELL POOL FROM BIRTH
TO ADULTHOOD
D. Dingli, 1 J.M. Pacheco2 1 Mayo Clinic, ROCHESTER, USA; 2 University of Lisbon, LISBON, Portugal
Background. Hematopoietic stem cells (HSC) are the targets of a variety
of genetic disorders, both inherited and acquired that can lead to
either marrow failure or neoplastic proliferation. The risk of acquiring
mutations is related to the replication rate, mutation rate and the population
of stem cells at risk. It is thought that only a fraction of the HSC
are actively contributing to hematopoiesis and it is this fraction that is
at highest risk of acquiring mutations. Aims. To determine the size of the
active HSC pool (NSC) from birth to adulthood. Methods. HSC contribute
to formation of all types of blood cells. Hence, the total circulating
reticulocyte count is a marker of the size of the active HSC pool for
any adult mammal. We determined the total number of circulating reticulocytes
in adult mammals across 40 species and correlated this with
their average mass. NSC should scale in the same way with mass. Utilizing
the known size of the active stem cell pool in cats, we can determine
the size of the active HSC pool in any mammal including adult
humans. We utilize a similar relationship for humans during growth to
estimate how the HSC pool expands from birth to adult life. Results. In
12 th Congress of the European Hematology Association
adult mammals, including humans, the active stem cell pool scales with
mass as NSC ~ M 3/4 while during human growth, NSC ~ M. Using the
known size of NSC in cats, we estimate that an adult human (M~70kg)
has an active stem cell pool, NSC ~385 cells, while a newborn (M~3.5kg)
has NSC~22 cells. In addition, using data obtained from transplantation
in cats suggests that in adult humans, the average size of NSC~116 after
a bone marrow transplant. We estimate that HSC replicate approximately
1/year. Our results are in excellent agreement with published reports
on informative patients with chronic granulomatous disease and after
marrow transplantation respectively. Summary/Conclusions. The active
hematopoietic stem cell pool is small in humans and it expands linearly
with mass during ontogeny growth. HSC replicate slowly and this may
be one mechanism to decrease the risk of acquiring mutations in a pool
of cells that contribute to hematopoiesis for many years.
0996
PRE-TRANSPLANT MYELOFIBROSIS IS INVERSELY CORRELATED WITH
THE DEVELOPMENT OF EXTENSIVE CHRONIC GRAFT-VERSUS-HOST DISEASE
IN PATIENTS WITH MYELOID MALIGNANCIES AFTER REDUCED INTENSITY STEM
CELL TRANSPLANTATION
M. Yoo Hong, Y.R. Kim, I.H. Park, S.H. Yoon, S.J. Kim, H.W. Lee,
D.Y. Hwang, J.S. Kim, J.W. Cheong
Yonsei University College of Medicine, SEOUL, South-Korea
Background. Secondary myelofibrosis (MF) frequently occurs in patients
with hematologic malignancies and successful treatment of underlying
disease has resulted in the reversal of bone marrow fibrosis. MF in
patients with acute leukemia has been regarded as an adverse prognostic
factor, attributable to the possible interference with marrow regeneration
after transplantation. However, the clinical significance of secondary
MF in reduced intensity stem cell transplantation (RIST) has not been
fully evaluated. Aims. We evaluated the effects of pre-transplant MF on
the transplantation outcomes in patients with acute myeloid leukemia
(AML) or myelodysplastic syndromes (MDS) undergoing RIST. Methods.
We evaluated pre-RIST bone marrow MF grade using conventional
method (N= 39, median age 42.0). Donors were HLA-matched siblings
in 30 cases (76.9%) and HLA-matched unrelated volunteers in 9 (23.1%).
Eleven (28.2%) patients received bone marrow and 28 (71.8%) received
G-CSF-mobilized peripheral blood. All patients received fludarabinebased
conditioning regimens combined with busulfan (82.0%),
cyclophosphamide (10.3%) or melphalan (5.1%). Cyclosporin A or FK506
was used for graft-versus-host disease (GVHD) prophylaxis. Patients were
divided into two groups according to the existence of pre-transplant MF
(20 as non-MF group and 19 as MF group). Results. Number of total nucleated
cells and CD34 + cells infused was not different between two groups.
Engraftment was documented 11 days after RIST in non-MF and 13 days
after RIST in MF group (p=0.528). The platelet recovery was not different
according to the MF. Graft failure was totally documented in 3 cases
(7.7%) which all had advanced disease status in the absence of MF. There
were no differences in the incidence of acute GVHD, bacterial or fungal
infections, and cytomegalovirus (CMV) infection according to the MF.
However, the incidence of extensive chronic GVHD was significantly
lower in the MF group compared to the non-MF group (11.2% vs 40.7%;
p=0.035). Relapse rate and non-relapse mortality were not different
according to pre-transplant MF (p=0.060 and p=0.350, respectively).
Extensive chronic GVHD significantly correlated with increased eventfree
survival rate (p=0.01). Multivariate analysis revealed that pre-transplant
MF significantly associated with reduced risk of extensive chronic
GVHD (odds ratio 0.107, 95% CI 0.014'0.838, p=0.033). Conclusions. Pretransplant
MF was significantly associated with reduced risk of extensive
chronic GVHD after RIST. The underlying immunologic mechanisms
should be further evaluated.
0997
BONE MARROW TRANSPLANTATION IN A GIRL WITH HERMANSKY-PUDLAK SYNDROME
AND LEUKEMIA
P. Brons, N. Meijer, H. Verbrugge, P. Hoogerbrugge
Radboud Univ. Nijmegen Medical Centre, NIJMEGEN, Netherlands
Introduction. Hermansky-Pudlak syndrome (HPS) is a rare, autosomalrecessive
disorder characterized by oculocutaneous albinism and bleeding
tendency caused by a platelet storage pool disease. The patient
reported here also suffered from acute myeloid leukemia (AML). To our
knowledge a correlation between HPS and leukemia has not been reported.
As the patient was transplanted for her AML we could also study the
effect of BMT on the bleeding disorder associated with HPS. Case report.
haematologica/the hematology journal | 2007; 92(s1) | 369