P188 The effect of killer immunoglobulin-like receptor genes on clinical outcome after hematopoietic stem cell transplantation

Abstract

Aim To investigate the effect of donors’ inhibitory and activating KIR genes on the clinical outcome in patients receiving hematopoietic stem cell transplantation for different hematological malignancies. Effects of 2DS4 allelic variants 2DS4f (001/011/014/015/016) and 2DS4d (003/004/006/007/008/009/010/012/013) were analyzed as well. Methods Retrospective analysis on 32 HSCT recipient/donor pairs transplanted at RUMC was conducted. Detection of all 16 known KIR genes in the donors was done by PCR-SSOP. The outcomes, overall survival (OS) and occurrences of grade II–IV GvHD were assessed using time-to-event analysis and Fisher exact test. Results KIR genes 2DL1, 2DL4, 2DP1, 3DL2, 3DL3 and 3DP1 were detected in all donors. Frequencies of other KIR genes in our donor cohort were 2DL2 (n = 14, 43.8%), 2DL3 (n = 30, 93.8%), 2DL5 (n = 21, 65.6%), 2DS1 (n = 17, 53.1%), 2DS2 (n = 15, 46.9%), 2DS3 (n = 12, 37.5%), 2DS5 (n = 15, 46.9%), 3DL1 (n = 31, 96.9%), 3DS1 (n = 20, 62.5%). Allelic distribution of 2DS4 was assessed in 31 patients and 2DS4 functional gene was not detected in 15 patients (48.4%), 3 were KIR2DS4f homozygous (9.7%) and 13 were 2DS4 heterozygous for both full and deleted version (41.9%). The median follow up was 476 (30–1879) days. The median survival was estimated to be 1151 days and 19/32 (59%) had >1 year survival. Significantly higher OS in HSCT recipients was noted when the donors had 2DS4f and 2DS4d compared to OS in those HSCT recipients with donors who had only 2DS4f gene (median not reached vs 162 days; p = 0.003). The OS of HSCT recipients when the donors had no 2DS4 (1151 days) and the OS of those who had donors with 2DS4 (162 days) were not different statistically (p = 0.19). Significantly higher OS was also seen in presence of 2DL3 (1151 days vs 106 days, p = 0.013) and absence of 2DL5 (median not reached vs 210 days p = 0.032). Presence of 3DS1 in the donor showed a positive trend towards one year survival (p = 0.062). Individual KIR genes did not influence GvHD. The 2DS4 gene variants also did not have significant effect on GvHD (p = 0.37). Conclusions Further mechanistic studies to explain the differential effects of inhibitory and activating KIR genes on OS of HSCT recipients are required. Higher OS seen in those who had donors with 2DL3, without 2DL5 and with 2DS4 heterozygous (2DS4f + 2DS4d) could lead to mechanistic approaches.