The CTG18.1 repeat expansion may reduce gene expression of TCF4 and ZEB1, suggesting that a mechanism triggering a loss of function may contribute to FECD. The correlation of CTG18.1 repeat expansion from blood and the cornea may represent the first step toward investigating the potential relevance of testing the blood of cornea donors to minimize the risk of transplanting grafts potentially affected with FECD.

An expanded TGC allele with more than 50 TGC repeats in intron 2 and the described risk allele G of the polymorphism rs613872 in intron 3 of the TCF4 gene appear as an association to FECD. The chance to be affected by FECD is up to 30 times higher. With molecular genetics also donors with clinically unknown FECD may be detected.

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Introduction: Keratinocyte Growth factor (KGF) prophylaxis reduces the extent and duration of mucosal barrier injury following intensive chemotherapy. Following this prophylaxis a marked reduction of infections and consecutively the need for antibiotic treatment can be observed. The extent of oral mucositis (OM) is easely to access. The extent of instestinal musocitis (IM) is more difficult to determine: The serum level of Citrulline, an intermediate product of the uric acid cycle mainly synthesized in the small intestine, serves as a marker of small intestine injury. Aim of the present study was to determine the extent of OM and IM before and after the introduction of KGF-prophylaxis in their treatment. METHODS: In 09/2006 KGF (60μg/kg body weight per day, for 3 days before conditioning therapy respectively after HSCT) was introduced at our institution on a compassionate use basis. Five months before the introduction and thereafter the extent of OM and IM in autologous and allogeneic HSCT was evaluated prospectively. Beside routine clinical and laboratory values including the daily oral mucositis score (DMS) and daily gut score (DGS) the plasma citrulline level was determined in week 1 (W1), week 2 (W2) and week 3 (W3) following HSCT. Moreover the dosage of therapeutic intravenous (i.v.) antibiotic treatment with meropeneme, piperacilline/combactam and teicoplanin in addition to antibiotic prophylaxis was noted. Pt with oropharyngeal radiotherapy were excluded from analysis. RESULTS: Until 04/2007 36 pt were evaluated. 27 pt underwent autologous and 9 allogeneic HSCT. 13 of the autologous and 6 of the allogeneic transplanted pt received KGF. In pt with KGF clinically significant OM and moderate to severe IM were seen less often (W1: 1/19 pt vs. 3/17 pt and W2: 1/19 pt vs. 2/17 pt without KGF). These differences were statistically non significant. Citrulline serum levels (in μmol/l) were significantly higher in pt receiving KGF (W2: average 16.8 vs. 15.9 in pt without KGF (p = 0.02)). The therapeutic use of i.v. antibiotics was lower for pt receiving KGF (average of 10.5 days vs. 26.8 days for pt without KGF (p = 0.0001)). Subgroup analysis confirmed the described tendencies in autologous HSCT. SUMMARY: Even in this small number of pt a positive effect of KGF on oral and intestinal mucositis was detectable. The reduced need for therapeutic i.v. antibiotics seen as a tendency in this study should be re-evaluated in a prospective pharmacoeconomic study to prove cost effectiveness of KGF treatment.