Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation

Abstract

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). HLAidentical BMT was performed for patients with acute (n ‫؍‬ 39) or chronic leukemia (n ‫؍‬ 68). 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 Fc␥RIIa 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 Fc␥RIIIb 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 Fc␥RIIIb 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. (Blood. 2002;100:3908-3918)

Influence of mannose-binding lectin genotypes and serostatus in allo-SCT: analysis of 131 recipients and donors

“…Donations of livers (the main MBL source) from variant donors to wild-type recipients resulted in rapidly decreasing MBL serum levels. 21 This is in line with earlier studies 22 in which donors' genotypes did not influence transplant-related complications. Therefore, it is unclear how to explain the findings of Mullighan et al and Granell et al 10,12 that transplantation outcome depended on MBL genotypes of both recipients and donors.…”

Association of MBL gene polymorphisms with major bacterial infection in patients treated with high-dose chemotherapy and autologous PBSCT

“…11,12 An association of MBL deficiency and infection is also reported in patients treated with conventional chemotherapy 13,14 or high-dose myeloablative chemotherapy followed by allogeneic stem cell transplantation, 15 which is not confirmed by others. 16,17 In the present study, we report an increased risk of major bacterial infection in patients carrying the MBL polymorphism when treated with high-dose chemotherapy (HDT) followed by autologous peripheral blood stem cell transplantation (auto-PBSCT). In addition, the allele frequencies of the MBL polymorphism in a total of 2623 healthy individuals were determined in seven different areas in Japan, which is, to our knowledge, the largest scale of study for MBL polymorphism in a single ethnic group.…”

“…It has recently been demonstrated that MBL deficiency is a genetic risk factor of infection in patients treated with HDT and allogeneic stem cell transplantation, 15 which was not confirmed by others. 16 As a variety of complex factors other than MBL polymorphism such as the effect of donor cells should be considered in allogeneic stem cell transplantation, HDT and auto-PBSCT will provide a clearer model to analyze the contribution of MBL polymorphisms to infection after myeloablative treatments. The condition with more reduced dose of chemotherapy, conventional-dose chemotherapy without stem cell support, has been demonstrated to be at an increased risk of infection or prolonged fever in several reports, 13,14 but not by others.…”

Relationship between TNFA, TNFB and TNFRII gene polymorphisms and outcome after unrelated hematopoietic cell transplantation in a Chinese population

“…27,28 Two previous studies failed to find an association between the TNFB þ 252 polymorphism and aGVHD. 29,30 The results of this study provide the first evidence that TNFB þ 252 G allele-positivity of recipients and/or donors was associated with an increased susceptibility to aGVHD in a Chinese population. The role of TNF-b in aGVHD is much less well known than that of TNF-a.…”