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

0588
EXTRACORPOREAL PHOTOPHORESIS FOR TREATMENT OF ACUTE GVHD IN
PAEDIATRIC PATIENTS
L. Rivabella, G. Tripodi, L. Scarso, M. Risso, G. Morreale, E. Lanino,
M. Faraci
Gaslini Children Institute, GENOVA, Italy
Background. Extracorporeal photophoresis (ECP ) represent a possible
and efficacious treatment in management of acute or chronic Graft versus
Host Disease (aGvHD/cGvHD) resistant to first line treatment consisted
in steroid therapy given to low (2 mg/Kg/day) or high dose
(5mg/Kg/day). Methods. In our department ECP was used to treat drug
resistant acute and chronic GvHD, to reduce the early and late steroid
toxicity and to increase the immunological reconstitution until to
decrease the incidence of opportunistic infections. ECP (1,5 TBV utilizing
COBE Spectra Auto PBSC6.1) was administered according to a schedule
consisted in 2 cycles/week for the first month, 2 cycles/every 15 days
for the second month and 2 cycles/month for the following 4 months.
Results. During the period between 2000-04, we enrolled 14 children
(median age 9.3 yrs) affected by aGvHD after an allogeneic haematopoietic
stem cell transplantation. ECP was administered to cure aGvHD
(global grade 1 = 8 pts, grade 2 = 3 pts; grade 4=1 pt) treated with steroid
therapy (2 mg/Kg/day in 8pts, 5 mg/Kg/day in 6pts) or to maintained a
CR obtained with steroid (2 pts). Steroids were associated to other
immunosuppressive therapies in 3 pts (anti CD25 in 2 pts and anti-TNF
in 1). We evaluated the response to ECP at the end of first, second and
six months of treatment. After the 1st month of ECP, 7/14 pts improved,
4/14 pts not responded, while 3/14 pts worsened. At the end of 2nd
month of ECP, 12/14 pts raised CR of aGvHD (3 pts received other
immunosuppressive therapies), 1 pt showed a grade 1, and 1 a grade 2
of aGvHD. The cGvHD evaluated at the end of ECP schedule (after 6
months) was absent in 11/14 pts, it was limited in 1/14 pts and extensive
in 2/14 pts. After 6 months, 6 pts received ECP for relapse of cGvHD
(4/6) or for a consolidation of CR obtained after a first treatment (1/6) or
to reduce the immunosuppressive therapy (remaining 1). Five pts died
:2 for cGvHD, 2 for sepsis and 1 for relapse of underlying disease. 6 pts
without a relapse of cGvHD are alive and they are in CR, 2 of pts who
not relapsed of cGvHD died for haematological relapse. Conclusions. We
confirm that ECP represent an efficacious treatment of aGvHD also in
paediatric patients. No events adverse were observed in our populations.
In our experience the major response was obtained after the first 2
months of therapy, when ECP was administered more frequently, in
particular the patients who obtained a CR during this first period rarely
developed a cGvHD. Patients who relapsed after a complete treatment
of ECP and who were treated with a new ECP treatment not obtained
a improved of cGvHD (2 of them died for cGvHD). We suggested that
probably ECP cycles should be increase in the first months of treatment
until to obtained a better and prolonged response.
0589
INFLUENCE OF NON-HLA GENETIC POLYMORPHISMS ON THE INCIDENCE OF GRAFT-
VERSUS-HOST DISEASE AND MORTALITY AFTER ALLOGENEIC STEM CELL
TRANSPLANTATION
G. Reddiconto, 1 P. Chiusolo, 2 A. Fiorini, 2 G. Farina, 2 S. Marietti, 2
S. Bellesi, 2 S. Giammarco, 2 D. De Ritiis, 2 L. Laurenti, 2 A. Catalano, 2
G. Leone, 2 S. Sica2 1 2 Università Cattolica del Sacro Cuore, ROME; Università Cattolica S. Cuore
Hematology, ROME, Italy
Hematopoietic stem cell transplantation (HSCT) may be associated
with a variety of complications such as graft-versus-host disease (GVHD)
and major non infectious transplant-related complications. Although
HLA compatibility has a central role in selecting donors and determining
transplant outcome, the sequencing of human genome has revealed
numerous non HLA single nucleotide polymorphisms (SNPs), whose
significance in allogeneic HSCT could be relevant. Due to these polymorphisms,
patients may be predisposed to releasing high levels of certain
cytokines pre and post trasplant during the cytokine storm and therefore
may be more predisposed and/or protected from GVHD and mortality.
In our study we examined the association of SNPs at position 677 and
1298 in the MTHFR gene, at -308 in the TNF α gene and -252 in the TNF
β gene, at -1082 and -592 in the IL10 gene, at -238 in the IL10 receptor
gene and at 908, 702, 1007 in the NOD2/CARD15 gene, on incidence of
GVHD (grade II-IV) and mortality in a group of 42 patients submitted to
allogeneic HSCT in our Institute from 2004 and in their donors respectively.
Variant genotypes were determined using PCR/restriction frag-
12 th Congress of the European Hematology Association
ment length polymorphisms, except for variant 1007 and 702 determined
using allele-specific PCR. Table 1 presents patients’ characteristics.
Kaplan Meyer incidence curves, with differences compared by the
Log-Rank test, were used to assess the association between polymorphisms
and clinical covariates (age, disease status, regimen conditioning,
gender compatibility, HLA mismatch) and GVHD development and
mortality. The level of significance was performed to p