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Prepublished online as a Blood First Edition Paper on July 25, 2002; DOI 10.1182/blood-2002-04-1033.
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Blood, 1 December 2002, Vol. 100, No. 12, pp. 3908-3918
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Host defense and inflammatory gene polymorphisms are associated
with outcomes after HLA-identical sibling bone marrow
transplantation
Vanderson Rocha,
Rendrik F. Franco,
Raphaël Porcher,
Henrique Bittencourt,
Wilson A. Silva Jr,
Aurelien Latouche,
Agnès Devergie,
Hélène Espérou,
Patricia Ribaud,
Gérard Socié,
Marco Antonio Zago, and
Eliane Gluckman
From the Hematology Department and Bone Marrow
Transplant Unit and the Biostatistics Department (INSERM U444),
Hôpital Saint Louis, Paris, France; and Center for
Cell Therapy, Faculty of Medicine of Ribeirão Preto,
Brazil.
We made the hypothesis that donor and recipient gene polymorphisms
that drive the host response to microorganisms could be associated with
infections after bone marrow transplantation (BMT). HLA-identical BMT
was performed for patients with acute (n = 39) or chronic leukemia
(n = 68). Genotyping was performed in 107 D/R DNA pairs for gene
polymorphisms of cytokines (tumor necrosis factor- [TNF-]
and TNF- , interleukin-1 receptor antagonist [IL-1Ra], IL-6, and
IL-10), adhesion molecules (CD31 and CD54), Fc receptors (FcRIIa,
IIIa, IIIb), mannose-binding lectin (MBL), and myeloperoxidase (MPO).
First infection (overall) and first episodes of bacterial, viral, or
invasive fungal infection were studied retrospectively for 180 days
after BMT. Univariate and multivariate analyses, using death as
a competing event, were performed to study risk factors. In
multivariate analysis, first overall infections were increased in
patients with the FcRIIa R-131 genotype (hazard ratio
[HR] = 1.92; P = .04), and severe bacterial
infections were increased when the MPO donor genotype was AG or AA
(HR = 2.16; P = .03). Viral and invasive fungal
infections were not influenced by any genetic factor studied.
Interestingly, we also found that (1) time to neutrophil recovery was
shorter when donors were FcRIIIb HNA-1a/HNA-1b
(HR = 1.77; P = .002); (2) donor IL-1Ra (absence of
IL-1RN*2) increased the risk for acute graft-versus-host disease (GVHD)
(II-IV) (HR = 2.17; P = .017); and (3) recipient IL-10
(GG) and IL-1Ra genotypes increased the risk for chronic GVHD
(P = .03 and P = .03,
respectively). Finally, 180-day transplantation-related mortality rates
were increased when donors were FcRIIIb HNA-1a/HNA-1a or
HNA-1b/HNA-1b (HR = 2.57; P = .05) and donor MPO
genotype was AA (HR = 5.14; P = .004). In conclusion,
donor and recipient gene polymorphisms are informative genetic risk
factors for selecting donor/recipient pairs and could help in the
understanding of mechanisms involved in host defenses of BM
transplant recipients.
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