Invasive aspergillosis (IA) remains a major cause of morbidity and mortality in pts undergoing alloSCT. The association between single nucleotide gene polymorphism (SNP) of components of the innate immune system and the risk for IA development has been reported recently. Objective: analysis of molecular risk for IA development in pts with acute leukemias undergoing alloSCT based on gene polymorphism studies. Material and methods: Gene-candidates (TLR4, DECT1, IFNG, TNFR2) were based on published data and our previous research. The primer for TLR4 SNP was designed using Lasergene Primer Select. IFNG, TNFR2 and DECT1 polymorphisms were screened with published primers. PCR conditions were common to all reactions. Gene polymorphisms were analyzed in a cohort of 90 pts with primary or secondary AML (64) or ALL (26) and their sibling (36) or unrelated (54) donors. Pts were conditioned with myeloablative (54) or RIC (36) regimen and grafted with 3.5 (0.8-5.2)x10^6/kg of CD34+ cells. Standard definitions for neutropenic, bacterial, fungal and viral infections were used. Results: neutrophil recovery occurred in all pts at a median 22 (range; 13-36) days with complete donor chimerism by day +30. Infectious complications included neutropenic fever in 81 (90%), CMV infection in 39 (43.3%) and documented IA in 22 (24.4%) pts (proven-4 and probable-18). Acute GVHD 2-4 grade was seen in 26 (29%), while chronic extensive in 9 (10%) pts. Among pretransplant factors (donor/recipient gene polymorphisms, age, sex, disease stage) the only significant factor for development of documented IA, by multivariate logistic regression analysis, was donor DECT1 SNP (p=0.016, HR 5.7). Among transplant-related factors (dose and source of stem cells, intensity of conditioning, neutropenia duration, GVHD) significant for IA development was CMV infection (p=0.021, HR=5.3). Over a median follow-up of 26.5 (range; 2.5-77.5) months, 65 (72.2%) pts were alive with median survival 27.5 (95%CI=5.0-78.9) months. Among 25 (20%) deaths, 8 were related to IA. None of analyzed factors was significant for death from infections. No factors predicting the outcome of IA pts were identified. Conclusion: Our data suggest that the donor DECT1 SNP may be used as a prognostic factor for IA development in acute leukemia pts after alloSCT. SNP profile, performed with easy and cheap assay, may guide antifungal prophylaxis and preemptive treatment in this group of patients.
Full conference title:
- EBMT 39th (2013)