Gene Polymorphism Profile May Predict Late Complications In Patients Undergoing Allogeneic Stem Cell Transplantation

Abstract

Gene polymorphism analysis may predict infection development, especially invasive fungal disease, in recipients of allogeneic stem cell transplantation (alloSCT), as previously reported (Gil et al., BMT 2013). It is also suggested that gene polymorphism may contribute to non-infectious complications occurrence. ObjectiveAnalysis of late complication after alloSCT with respect to gene polymorphism profile. Material and MethodsAnalysis for infectious or non-infectious complications was performed in a cohort of 126 adult patients (pts) with acute leukemias (94), chronic leukemias (10) or lymphoid malignancies (22) who underwent alloSCT and survived at least 100 days. All pts and their sibling (58) or unrelated (68) donors were previously screened for TLR4, IFNG, TNFR2 and DECT1 single nucleotide polymorphisms (SNP). The primer for TLR4 SNP was designed using Lasergene Primer Select. IFNG, TNFR2 and DECT1 polymorphisms were screened with published primers with PCR conditions common to all reactions. Patients were conditioned with myeloablative (58) or reduced intensity (68) regimen and grafted with 3.8 (0.8-5.2)x10^6/kg of CD34+ cells. Standard definitions for relapse, graft versus host disease (GVHD) and infections (neutropenic, bacterial, fungal and viral) were used. ResultsInfectious complications that occurred after 100 days posttransplant included bacterial infection in 28 (22%), CMV infection in 19 (15%) and invasive fungal infection in 12 (9%) pts. Late onset acute GVHD 2-4 grade was seen in 15 (12%), while chronic extensive GVHD in 18 (14%) pts. Relapse was diagnosed in 30 (24%) pts. Secondary malignancies were observed in 2 pts. Over a median follow-up of 34.5 (range; 6-85.5) months, 90 (71%) pts were alive with median survival 35.5 (95% CI=8-87) months. Among genetic factors by multivariate logistic regression analysis donor DECT1 SNP was significant for fungal infection development (p=0.016, HR 5.7); chronic GVHD development (p=0.038, HR=4.4) and death from chronic GVHD (p=0.028; HR=4.8). Additionally, donor INFG SNP was significant for CMV occurrence (p=0.019; HR=5.5). None of studied polymorphisms had impact on the outcome. Among transplant-related factors (age, sex, diagnosis, disease stage, dose and source of stem cells, type of transplant, intensity of conditioning, neutropenia duration) only alloSCT from unrelated donor was significant for late CMV infection (p=0.47; HR=3.9) and bacterial infection (p=0.036; HR=4.4) development. ConclusionOur results suggest that gene polymorphism profile may predict late infectious and non-infectious complications in patients undergoing alloSCT. It may influence stratification of pts to offer an individualized therapy. Disclosures:No relevant conflicts of interest to declare.