Results of Simultaneously Performed Analysis of 48 Gene Variants Reported to Have Influence on Transplant outcome

Abstract

Abstract 3047Up to date, there are many conflicting reports existing in which different gene variants have been proposed to have influence on the outcome of allogeneic transplant. Hereby many of the published studies bare a distressing high weakness in the study set up as for example low number of study patients, large heterogeneity of donor types and/or GVHD prophlyaxis regimens and/or T cell depleting of grafts and/or type of conditioning regimens. In this study we aimed to evaluate in 285 patients and their HLA identical sibling donors the following in table 1 shown 48 different gene variants from which were reported to have influence on the outcome of transplants. Our study group consists of a homogenous group of patients who underwent all a non T cell-depleted transplantation after receiving a myeloablative conditioning regimen and a GVHD prophylaxis with MTX and CSA or CSA and MMF. Patients were transplanted from a HLA-identical sibling donor for various diseases like acute leukemia, CML, MDS, lymphoma and MM between January 2000 and June 2010 at our centerWe could confirm an influence of gene variants of NOD2 (80, 4% vs 61, 6%, p=0.0013), IL23R, MTHFR1298, and LCT 13910 on the occurrence of acute GVHD grade 1–4 on recipients side, whereas no influence was seen of any gene variant on the occurrence of grade 2–4 acute GVHD. But, NOD2 gene variants had a significant (p=0.041) influence on the occurrence of severe acute GVHD grade 3–4. The occurrence of acute GVHD grade 1–4 was significantly modified by the detection of following gene variants at donors side: CCL5 28 promotor (30, 8% vs 69, 2% p=0.033), GSTP 313 (74, 3% vs 62, 4%, p=0.043);IL23R (69, 9% vs 48%, p=0.049), MTHFR129 (86, 7 vs 37, 3% p=.0.06), MTHFR 677 (53, 8% vs 70%, p=0.05), NOD2 (65, 9% vs 84, 4%, p=0.01). Acute GVHD grade 2 –4 was significantly influenced only by GSTP (p<0.015) and MTHFR129 (p<0.025). Severe acute GVHD grade 3–4 was only influenced by GSTP gene variants (p<0.04).The 5-year TRM was influenced by MTHFR677 (30, 4% vs 19, 2%, p=0.05) at recipient side, and at donor side by the genes IL18 Rap (38, 5% vs 19%, p=0.046) and CYP1B1 (28, 8% vs 15, 6%, p=0.07).IL10 gene variants at recipients side influenced the 5-year OS significantly, at donor side the 5-year OS was influenced by CTLA4 (69, 4 vs 52, 2%, p=0.06) IL23R (53, 6% vs 71, 6%, p=0.044) and MBL2CD55 48, 9% vs 65, 2% p=0.02).In this study we could confirm that the above described gene variants might influence moderately the transplant outcome and may therefore be qualified for screening in patients and their respective donors prior to transplant.CCL5 28 promotor G/Crs1800825MBL2 Codon220rs7096206CCR5 2086 A/Grs1800023MBL2 Codon4rs7095891CCR5 2554 G/Trs2734648MBL2 Codon550rs11003125CP2C19*2rs4244285MBL2[G54D]rs1800450CP2C19*3rs4986893MBL2[G57E]rs1800451CTLA4 A/G pos.49rs231775MBL2[R55C]rs5030737CYP1B1 432rs1056836MCP1 1543 C/Trs13900CYP2C9*2rs1799853mdr1 C3435Trs1045642CYP2C9*3rs1057910MTHFR1298rs1801131CYP2D6*3rs4986774MTHFR677rs1801133CYP2D6*4,rs1800716NFKBIL1rs2857605CYP2D6*6rs5030655NOD2 G908Rrs2066847CYP3A4*1BNOD2 L1007F insCrs2066847CYP3A5*3NOD2 R702Wrs2066844FAS 670 G/Ars4934436TLR2 R753Qrs5743708GSTA1 A567T, 69C 52Grs3957356TLR3rs3775291GSTP1 313A/Grs1695TLR4 [D299G]rs4986790IL10 -1082rs1800896TLR4 [T399I]rs4987233IL10 592 C/Ars1800872TLR5rs764535IL23RTLR6 745C>Trs5743810IL18 137 G/Crs187238TLR9 C-1237Trs5743836IL18 RAPrs917997TLR9 T-1486Crs187084IL6 G174Crs1800795TNF alpha 238 A/Grs361525LTArs2844484VEGF 405G/Crs833061 Disclosures:No relevant conflicts of interest to declare.