Different Panel of Gene Variants Influence Outcome of Transplant From Sibling Donors Compared to HLA-Identical Unrelated Donors

Abstract

AbstractAbstract 4182 Introduction and methods:In two different study populations with sibling (SIB) or unrelated (URD) HLA-identical donors we evaluated the role of 48 different genes (table1) reported to have influence on the outcome of allogeneic transplant and compared them between the transplant settings. 314 patients and their HLA identical URD and 285 patients and their HLA-identical SIB donors were analyzed after T cell repleted myeloablative transplantation and use of GVHD-prophylaxis with only MTX and CSA or CSA and MMF. Patients were transplanted for acute leukemia, CML, MDS, lymphoma and MM between Jan. 2000 and June 2011 at our center. Results:In the URD-cohort the occurrence of acute GVHD grade 2–4 was influenced adversely by gene variants on recipient side of LTA (40% vs 28%, P=0.013), MBL2 codon550 (47% vs 31%, P= 0.03), MCP1 (69% vs 42%, p=0.03) and NFKBIL1 (51% vs 34%, P=0.02). Further, the occurrence of severe aGVHD 3–4 was influenced adversely by gene variants of MBL codon 550 (10% vs 23%, P= 0.025), MBL2 codon 4 (10% vs 36% P=0.04), LCT13910 (9% vs 26%, P= 0.04) and CYP1B1 (8% vs 20%; P=0.05). Favorable effect was induced by a gene variant of IL6 on aGVHD 3–4 (4% vs 19%, P=0.04) in the URD setting, whereas NOD2 gene variants, but none of these gene variants had influence on aGVHD in the SIB cohort.Further, we found that the rate of 5-year none-relapse mortality (NRM) was associated adversely with the detection of variants of IL16 (60% vs 34%, P=0.01) and MCP1 (58% vs 27%, P=0.02), which influenced the 5-year estimate for overall survival (OS) of patients (MCP1 40% vs 53%, P=0.01 and IL16 46% vs 28%, P=0.03) in the URD setting.On donor side the occurrence of aGVHD grade 2–4 was influenced by MBL2 codon4 (69% vs 32%, P= 0.007), TLR2 (66% vs 41%, P=0.02), TLR5 (75% vs 42%, P=0.041). AGVHD 3–4 was influenced by IL23R favorably (0% vs 20%, p=0.01) and adversely by IL18 (10% vs 36%; p= 0.01) in the URD setting.The 5-year NRM was associated with the detection of gene variants at donor side of CCR5 (53% vs 27%, p=0.01), CTLA4 (23% vs 44%, P=0.02), CYP1B1 (14% vs 26%, P=0.045), TLR2 (34% vs 66%, P=0.025). Also, IL10 gene variants at donor side influenced the 5-year OS significantly (23% vs 54%, p=0.03) as well as the gene variants TLR2 (28% vs 50%, P= 0.04), IL18 Rap (40% vs 72%, P= 0.03) and FAS (60% vs 36%, P=0.04).In SIB cohort the 5-year TRM was influenced by MTHFR677 (30% vs 19%, p=0.05) at recipient side, and at donor side by the genes IL18 Rap (39% vs 19%, p=0.046) and CYP1B1 (29% vs 16%,p=0.07). IL10 gene variants at recipients side influenced the 5-year OS, too. At donor side the 5-year OS was influenced by IL23R (54% vs 72%, p=0.04) and MBL2CD55 49% vs 65% p=0.02).In conclusion we report here that except IL23R and IL10 different panels of gene variants have influence on outcome of transplants from SIB donors compared to transplants from URD.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.