12th Congress of the European Hematology ... - Haematologica
12th Congress of the European Hematology ... - Haematologica
12th Congress of the European Hematology ... - Haematologica
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12 th <strong>Congress</strong> <strong>of</strong> <strong>the</strong> <strong>European</strong> <strong>Hematology</strong> Association<br />
to a poor prognosis in MM patients, reflecting a high tumour burden.<br />
Renal damage is uncommonly described in <strong>the</strong> absence <strong>of</strong> BJP. However,<br />
high prevalence for older age and cardiovascular disease in our population<br />
suggest potential o<strong>the</strong>r causes <strong>of</strong> renal involvement. So, renal<br />
impairment in <strong>the</strong> MM population needs a particular attention. Even in<br />
<strong>the</strong> absence <strong>of</strong> BJP, a mild renal dysfunction must be worthwhile examined<br />
for adequate haematological, cardiovascular and renal care. Cardiovascular<br />
disease and older age are common in our newly diagnosed<br />
MM patients. Ei<strong>the</strong>r BJP is present or absent, renal function is comparable.<br />
Mild renal dysfunction in MM patients could appear as a multifactorial<br />
entity, needing a multidisciplinary careful analysis for adequate<br />
assessment and treatment.<br />
1292<br />
VALGANCICLOVIR IS SAFE AND EFFECTIVE AS PRE-EMPTIVE TREATMENT FOR CMV<br />
REACTIVATION IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION<br />
R. Pastano, F. Gigli, G. Andreola, F.A. Peccatori, G. Martinelli<br />
<strong>European</strong> Institute <strong>of</strong> Oncology, MILAN, Italy<br />
Background. Despite significant advances in prevention and <strong>the</strong>rapy,<br />
cytomegalovirus (CMV) infection still represents an important cause <strong>of</strong><br />
morbidity and mortality in patients undergone allogeneic haematopoietic<br />
stem cell transplant (HSCT). The standard pre-emptive treatment<br />
is based on intravenous administration <strong>of</strong> Ganciclovir (GCV). Valganciclovir<br />
(VGC), <strong>the</strong> pro-drug formulation <strong>of</strong> GCV is characterised by an<br />
excellent bio viability, making this drug suitable for oral administration.<br />
Aims. To evaluate <strong>the</strong> safe and <strong>the</strong> efficacy <strong>of</strong> Valganciclovir as preemptive<br />
treatment for CMV reactivation in allogenic hematopoietic<br />
stem cell transplantation. Methods. Since March 2003 patients enrolled<br />
in our Institute to undergo allogeneic HSCT have been started CMVpre-emptive<br />
treatment with VGC, administrated in outpatient setting.<br />
Thirty patients were followed by weekly monitoring both <strong>of</strong><br />
CMV/PCR and pp65/assays. Patients resulted positive (3 cells pp65+ or<br />
1000/100000 PCR + ) started oral treatment with VGC 900 mg bid, for <strong>the</strong><br />
first fourteen days, followed by 900 mg q.d. up to at least seven days<br />
after assays negativization. Results. Overall 15 episodes <strong>of</strong> CMV positivity<br />
were detected in seven patients (all with sibling donors). In <strong>the</strong>se<br />
patients, <strong>the</strong> median duration <strong>of</strong> <strong>the</strong>rapy was 21 days (range 10-21<br />
days), with a response rate (RR) <strong>of</strong> 100%, as confirmed by <strong>the</strong> assays<br />
negativization within fourteen days. No significant toxicity was<br />
encountered. In two patients <strong>the</strong> oral VGC <strong>the</strong>rapy was changed to <strong>the</strong><br />
intravenous administration <strong>of</strong> Foscavir, because <strong>of</strong> concomitant neutropenia<br />
and acute GvHD. Conclusions. Pre-emptive treatment <strong>of</strong> CMV<br />
reactivation with VGC is safe and effective. Fur<strong>the</strong>rmore, <strong>the</strong> oral<br />
administration <strong>of</strong> this drug in outpatient setting, reduces significantly<br />
<strong>the</strong> costs compared with a <strong>the</strong>rapy that needs hospitalization as intravenous<br />
Ganciclovir.<br />
1293<br />
COMPARISON OF TWO METHODS OF HEMATOPOIETIC STEM CELL ISOLATION<br />
AND EVALUATION OF THE EX VIVO CULTURED AND DIFFERENTIATED CELLS<br />
WITH CDNA MICROARRAYS<br />
M. Klabusay, 1 V. Hrabcakova, 1 I. Koutna, 2 P. Krontorad, 2 J. Mayer, 1<br />
D. Horky2 1 2 University Hospital Brno, BRNO; Masaryk University, BRNO, Czech<br />
Republic<br />
Background. CD34 + cells are clinically used in transplantation <strong>of</strong> bone<br />
marrow or peripheral blood stem cells (PBSC) after conditioning regimens<br />
in patients with diagnosis <strong>of</strong> leukemia or lymphoma. The CD34 +<br />
cell count increases in peripheral blood after stimulation with granulocyte<br />
colony-stimulating factor (G-CSF). Hematopoietic stem cells are<br />
found within <strong>the</strong> compartment <strong>of</strong> CD34 + cells and <strong>the</strong>y are able to regenerate<br />
hematopoiesis in all <strong>of</strong> its lineages, as well as renew <strong>the</strong>mselves.<br />
Aims. We wanted to assemble a suitable method for evaluating gene<br />
expression in enriched populations <strong>of</strong> hematopoietic stem cells and compare<br />
<strong>the</strong>ir biological properties during ex vivo culture in time. Methods.<br />
We used two ways <strong>of</strong> immunomagnetic separation: positive selection<br />
<strong>of</strong> CD34 + cells and negative selection <strong>of</strong> Lin – cells. CD34 + and Lin’ cells<br />
were enriched from PBSC grafts <strong>of</strong> patients with non Hodgkin’s lymphoma.<br />
After <strong>the</strong> immunomagnetic separation, <strong>the</strong> cells were cultivated<br />
in <strong>the</strong> presence <strong>of</strong> cytokines stem cell factor, interleukin-3, interleukin-6,<br />
Flt-3-L and G-CSF in serum-free media in order to induce granulocytic<br />
differentiation. At days 0, 4, 6, 8, 10, 12 and 14 cells were harvested<br />
and analyzed by cDNA microarrays. O<strong>the</strong>r analyses included<br />
colony forming assays, immunophenotyping <strong>of</strong> <strong>the</strong> surface differentia-<br />
468 | haematologica/<strong>the</strong> hematology journal | 2007; 92(s1)<br />
tion antigens (CD13, CD33, CD34, CD36, CD65, CD116, CD117,<br />
CD123, CD124 a CD133), electron microscopy, vitality, total cell and<br />
CD34 + cell counts. Results. The purities <strong>of</strong> CD34 + cells after CD34 + and<br />
Lin – separation procedures were comparable. CD34 + expression was <strong>the</strong><br />
highest in <strong>the</strong> beginning <strong>of</strong> <strong>the</strong> cultivation and decreased rapidly in time.<br />
23.94±10.29 (average±s.d.) fold expansion <strong>of</strong> <strong>the</strong> CFU-GM and<br />
2.56±3.31 fold expansion <strong>of</strong> CFU-Meg in CD34 + cultures were reached.<br />
In Lin – cultures, 30.39±16.64 fold expansion <strong>of</strong> <strong>the</strong> CFU-GM and<br />
1.28±1.93 fold expansion <strong>of</strong> <strong>the</strong> CFU-Meg were observed. Comparison<br />
<strong>of</strong> gene expression maps <strong>of</strong> two different types <strong>of</strong> hematopoietic cell<br />
enrichment pointed to a suitability <strong>of</strong> cDNA microarray analysis <strong>of</strong> ex<br />
vivo cultured and differentiating hematopoietic cells. Equivalence <strong>of</strong> <strong>the</strong><br />
two enrichment methods from PBSC samples was demonstrated. Summary/Conclusions.<br />
Microarray analysis <strong>of</strong> <strong>the</strong> short-term ex vivo cultured<br />
hematopoietic cells enabled us to investigate up- and down- regulation<br />
<strong>of</strong> <strong>the</strong> gene expression during granulocytic differentiation. This methodological<br />
approach is helpful in characterizing ex vivo cultured cells, but<br />
it is also suitable for more general purposes. Equivalence <strong>of</strong> CD34 + and<br />
Lin – selection methods from PBSC samples proved by cDNA microarray<br />
may have an implication for graft manipulation in an experimental<br />
setting <strong>of</strong> hematopoietic stem cell transplantation.<br />
This work was supported by research grant MSM CR No. 0021622430.<br />
1294<br />
AN AUDIT ON THE USE OF 20% HUMAN ALBUMIN IN A TERTIARY CARE HOSPITAL<br />
G.A. Zakout, 1 M.A. Greiss2 1 Aberdeen Royal Infirmary, ABERDEEN; 2 Aberdeen Blood Transfusion Center,<br />
ABERDEEN, United Kingdom<br />
Background. The use <strong>of</strong> human albumin has been looked into for<br />
almost a decade. Most <strong>of</strong> <strong>the</strong> evidence we have comes from systemic<br />
review <strong>of</strong> randomised-controlled trials as well as meta-analysis. The<br />
main conclusions from such evidence were that current data suggest <strong>the</strong><br />
lack <strong>of</strong> evidence <strong>of</strong> mortality benefits from human albumin and<br />
increased cost when compared to cheaper alternatives such as crystalloids.<br />
Moreover, fluid resuscitation with albumin or saline produced<br />
similar outcomes irrespective <strong>of</strong> patients’ baseline serum albumin concentration.<br />
Certainly <strong>the</strong> use <strong>of</strong> albumin in <strong>the</strong> United Kingdom<br />
decreased by at least 40% following <strong>the</strong>se publications. Never<strong>the</strong>less<br />
<strong>the</strong>re is growing evidence to support <strong>the</strong> use <strong>of</strong> 20% human albumin<br />
in terms <strong>of</strong> mortality reduction in specific patient populations such as<br />
following large volume paracentesis in diuretic refractory ascites and in<br />
preventing renal failure in spontaneous bacterial peritonitis associated<br />
with cirrhosis. Aim. Based on this evidence, we ask through this audit<br />
how far does our hospital practice comply with <strong>the</strong> current data and<br />
what possible economic repercussions may result from inappropriate<br />
use. Methods. We carried out a retrospective review <strong>of</strong> all <strong>the</strong> requests<br />
for 20% human albumin, which North East <strong>of</strong> Scotland Blood Transfusion<br />
Service (NESNBTS) received from 1st May 2005 to 31st April<br />
2006 from <strong>the</strong> Aberdeen Royal Infirmary; a tertiary care hospital. The<br />
use <strong>of</strong> 20% human albumin was deemed appropriate in: 1. Ascites for<br />
drainage 2. Hepatorenal syndrome. 3. Spontaneous bacterial peritonitis.<br />
Results. NESNBTS received a total <strong>of</strong> 461 orders from <strong>the</strong> 1st May<br />
2005-31st April 2006 from different subspecialties at <strong>the</strong> Aberdeen Royal<br />
infirmary, which was mainly from <strong>the</strong> gastroenterology ward-around<br />
79% (n=364). 130 adult patients aged 19-92 years received a total <strong>of</strong> 1-<br />
77 vials. A total <strong>of</strong> 1056 total vials (each <strong>of</strong> which was 100ml) were<br />
issued . 4% (n=43) <strong>of</strong> <strong>the</strong> vials had to be discarded, as <strong>the</strong>y were not<br />
required after being dispensed to <strong>the</strong> ward (as per MRHA regulations).<br />
Indications ranged variably but paracentesis in cirrhotic patients was<br />
<strong>the</strong> most common - 66% (n=304) <strong>of</strong> <strong>the</strong> total orders. 81% (n=855) <strong>of</strong><br />
<strong>the</strong> total orders were considered appropriate. 14.96% (n=158) did not<br />
comply with evidence to support its use and this comes mainly from<br />
medical wards. The total expenditure for <strong>the</strong> amount <strong>of</strong> human albumin<br />
issued over <strong>the</strong> audit year was approximately £38300. It is estimated<br />
that approximately £4000 worth <strong>of</strong> human albumin has been wasted<br />
through discarded and inappropriately used vials. Summary. Our<br />
hospital practice is reasonably appropriate. This might well be due to<br />
<strong>the</strong> controlled 20% human albumin prescription by <strong>the</strong> medical <strong>of</strong>ficer<br />
at <strong>the</strong> NESNBTS. Although <strong>the</strong>se results are encouraging <strong>the</strong>re still<br />
remains space for improvement through fur<strong>the</strong>r educational measures.<br />
The use <strong>of</strong> 20% human albumin remains controversial even to this<br />
date. We still require more well-conducted, large scale, randomised<br />
controlled trials <strong>of</strong> sufficient statistical power to determine its indications.<br />
However till <strong>the</strong>n, we are bound to justify and rationalise its use.