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Bone Marrow Transplantation (2004) 34, 339344
& 2004 Nature Publishing Group All rights reserved 0268-3369/04 $30.00www.nature.com/bmtLack of IFN-gamma 2/2 homozygous genotype independently of recipient
age and intensity of conditioning regimen inuences the risk of aGVHD
manifestation after HLA-matched sibling haematopoietic stem cell
transplantationA Mlynarczewska1, B Wysoczanska1, L Karabon2, K Bogunia-Kubik1 and A Lange1,21L Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland; and 2Lower Silesian
Center for Cellular Transplantation & National Polish Bone Marrow Donor Registry, Wroclaw, PolandSummary:A total of 110 patients (71 adults and 39 children) who
received allogeneic haematopoietic stem cell transplantation from HLA-matched sibling donors were studied for
the incidence of acute graft-versus-host disease (aGvHD)
in relation to IFN-gamma gene microsatellite polymorphism. A strong tendency was observed towards the lower
incidence of grades IIIV aGvHDin patients having an
IFN-gamma 2/2 genotype as compared to the recipients
with other IFN-gamma genotypes (0.12 vs 0.33, P 0.06).
This relationship was independent of the intensity of
conditioning regimen and diagnosis. IFN-gamma polymorphic features, together with other clinical and
biological factors (patients age, donorrecipient gender,
diagnosis, conditioning regimen, transplant material and
GvHDprophylaxis), were subjected to multivariate
analysis for aGvHDmanifestation in order to exclude
indirect association of the IFN-gamma 2/2 genotype.
In multivariate analysis, myeloablative therapy
(OR 11.462, P 0.013), recipient age (OR 4.896,
P 0.009) and lack of IFN-gamma 2/2 genotype
(OR 4.311, P 0.048) were found to signicantly
contribute to the development of grade IIIV aGvHD,
while type of GvHDprophylaxis showed less-strong
inuence (OR 2.963, P 0.066). Thus, it appeared that
the IFN-gamma 2/2 genotype constituted an independent
and protective factor associated with a decreased risk of
grade IIIV aGvHD. However, this genotype was not
found to be associated with the risk of cGvHDor survival.
Bone Marrow Transplantation (2004) 34, 339344.
doi:10.1038/sj.bmt.1704581Published online 5 July 2004Keywords: IFN-gamma intron 1 polymorphism; (CA)n
microsatellite; aGvHD; HSCT
Allogeneic haematopoietic stem cell transplantation
(HSCT) is an effective therapeutic approach for the
treatment of haematological malignancies and nonmalignant haematopoietic disorders. Graft-versus-host disease
(GvHD) is one of the major complications occurring in
the recipients of allogeneic HSCT. IFN-gamma is a
cytokine strongly involved in perpetuation of this disease and plays the central role in donor and host cell
expansion.1Single-nucleotide polymorphism (SNP) and microsatellite polymorphism were detected in...