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

to asses intestinal epithelial damage we prospectively measured serum
citrulline levels - a marker of small bowel enterocyte mass - once weekly
during the course of HSCT (timepoints: day-12, -6, 0, +7, +14, +21)
in 11 consecutive palifermin treated patients receiving either an unrelated
or related donor. In a mouse model administration of palifermin
reduced aGVHD documented by preserved citrulline levels, indicating a
reduced injury to the gastrointestinal tract. In our patients median citrulline
serum concentration showed an expectable decline until day+7
(7.70 µM) - reflecting a maximal intestinal barrier injury - followed by
an adequate increase at day+21 (14.86 µM) which is in accordance with
untreated patients at our site (day+7: 9.02 µM, p=ns and day+21: 16.33
µM, p=ns) and a historical cohort receiving allo-sibling-HSCT following
myeloablative therapy. This lack of preserved gut integrity shown by an
equal decline of citrulline concentration may explain the absent reduction
of aGVHD rates. Conclusions. Palifermin in unrelated HSCT shows
a comparable safety profile to sibling donor transplants. However, we
could not find a favourable effect of palifermin on the incidence and
severity of aGVHD.
0464
THE DEVELOPMENT OF CELLULAR IMMUNITY TO ASPERGILLUS FUMIGATUS AFTER
ALLOGENEIC STEM CELL TRANSPLANTATION
D. Bensoussan, L. Clement, N. Daguindau, A. Salmon, F. Namour, M.
Machouart, V. Latger Cannard, V. Decot, C. Andre Botté, B. Fortier,
J.L. Guéant, T. Lecompte, J.F. Stoltz, P. Bordigoni
CHU de Nancy, NANCY, France
Background. Slow immune reconstitution after mismatched and match
unrelated donor transplantation results in a high mortality from viral
and fungal infections. Invasive aspergillosis (IA) is one of the major fungal
infections after hematopoietic stem cell transplantation (HSCT),
although new antifungal drugs have emerged. Part of the problem is the
failure to make an early molecular diagnosis, as for CMV. Invasive
aspergillosis incidence after HSCT is about 10%, variability depending
on environmental conditions. The mortality rate of IA is about 50 to
80%. It has been previously reported that a Th1-type cellular immune
response could favourably influence the IA evolution. Aims. We initiated
a study of cellular immune reconstitution against Aspergillus fumigatus
after HSCT where 70 patients have to be included. We present hereafter
the results of the 41 one first patients. Methods. Cell phenotype
analysis and proliferation capabilities against mitogens and Aspergillus
fumigatus conidies were performed at day 60, 100, 180 and 360 after
HSCT. Secretion of IL10 and IFNγ cytokines was also investigated. Finally,
antigen and molecular monitoring of aspergillosis infection were performed.
Results. Six patients presented antigenic or molecular evidence
of infection but only one developed an IA. Proliferation response against
Aspergillus fumigatus conidies improved regularly after day 60 to be
completely recovered at day 360. IFNγ level seemed to decrease during
the first year post-HSCT whereas IL10 level remained constant. The
patient who presented an IA at day 15 after HSCT was first unsuccessfully
treated with anti-viral drugs. He underwent two surgical procedures
at day 110 and day 160 which finally resulted in negativation of
biological evidence of aspergillosis and development of a proliferation
response against Aspergillus fumigatus conidies at day 265. However, no
cytokine secretion could be detected. Conclusions. The analysis of such
a cohort is interesting to better characterise how immune reconstitution
against Aspergillus fumigatus happens depending on transplantation
conditions.
12 th Congress of the European Hematology Association
0465
FLUDARABINE PHOSPHATE-BASED REDUCED INTENSITY CONDITIONING FOR
ALLOGENEIC STEM CELL TRANSPLANTATION IN PATIENTS WITH ACUTE MYELOID
LEUKEMIA, MYELODYSPLASIA AND CHRONIC MYELOID LEUKEMIA:
UPDATE OF A NATIONAL DOSE- FINDING STUDY
M.C. Ngirabacu, 1 P. Zachee, 2 J. Maertens, 3 K. Theunissen, 4 A. Ferrant, 5
C. Doyen, 6 L. Noens, 7 W. Schroyens, 8 D. Selleslag, 9 H. Demuynck, 10
R. Schots, 11 N. Meuleman, 1 D. Bron1 1 Institue Jules Bordet, BRUXELLES; 2 ZNA Campus Stuivenberg, ANTWER-
PEN; 3 U.Z. Gasthuisberg, LEUVEN; 4 UZ Gasthuisberg (Hematologie), LEU-
VEN; 5 Cliniques universitaires Saint-Luc, BRUXELLES; 6 UCL Mont Godinne,
YVOIR; 7 UZ Gent, GENT; 8 UZ Antwerpen, EDEGEM-ANTWERPEN; 9 AZ
St Jan, BRUGGE; 10 Heilig Hartziekenhuis vzw, ROESELARE; 11 AZ-VUB,
BRUXELLES, Belgium
Objectives. We prospectively studied the role of ATG in a Fludarabine
phosphate (F)-based non myeloablative conditioning regimen to control
the development of graft-versus-host-disease (GVHD), to accelerate
donor engraftment and to maintain graft-versus-leukemia (GVL) effects
in patients with myeloid malignancies not eligible for classical allogeneic
transplant. We also analyzed the outcome of the patients (pts) according
to their age and to the status for disease before transplantation. Population.
A total of 61 pts were enrolled in this phase I-II study. Pts were
conditioned with F (30 mg/m 2 /day for 4 days) plus cytarabine (2 mg/kg/d
for 4 days) or cyclophosphamide (1g/m 2 /day for 3 days). All pts received
cyclosporine (3-5 mg/kg IV, daily) and ATG 10 mg/kg/day either for 4
days (n=13), or for 2 days (n=7), or for 2 days + mycophenolate mofetyl
(n=38) or no ATG (n=3). Chimerism analyses were performed on d30,
45, 60 and 90. Results. 23AML, 22 MDS, 13 CML and 3 Myelofibrosis
(MF) were enrolled in this trial. The median age was 56.5 (18-75) years.
22 pts (36%) had 60 y.o. or more. The median follow-up is 41 (13-81)
months. Prior to transplantation, 51% of pts were in complete remission.
49% had persistent disease (PR, PD). Engraftment rate was 97%. The
occurrence of Acute GVHD (aGVHD) grade II-IV at day 90 was very low
in all groups (90%)
donor chimerism was achieved in 85% of the pts. 3 years OS and EFS
in all patients were respectively 55% and 44%. According to the age, OS
at 3 years seems to be better in young pts (60.5%) than in pts above 60
y.o (39%), p=0.07. For CML, OS and EFS at 3 year were 80% and 60%
respectively in young patients versus 0% in elderly pts. The comparison
of high risk pts (not in CR) and pts in CR didn’t show any difference in
term of OS or EFS. Primarily in diseases very sensitive to the GVL effect
(AML and CML), there were no significant differences in OS and EFS
curves according to the status before transplant. In AML and MDS pts,
a plateau in the EFS curve (respectively 43% and 40% /3 years) suggests
a cure in these pts. Conclusions. Although this series is too small to draw
definite conclusions, these observations suggest that in AML and CML
pts, RIC transplantation can be a curative option whatever the status of
disease before transplant. In MDS pts, the status before transplant
remains a prognostic factor and in CML pts, age (above 60) also has a
negative impact.
haematologica/the hematology journal | 2007; 92(s1) | 173