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BackgroundGaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy.Case presentationWe report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient’s spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient’s quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no adverse events have been reported.ConclusionsOral miglustat therapy proved to be a valid alternative treatment to intravenous enzyme replacement therapy for long-term maintenance in this patient with Gaucher disease type 1, who showed persistent allergic intolerance to imiglucerase infusions. This report exemplifies the type of patient with Gaucher disease type 1 who can benefit from switching from enzyme replacement therapy to substrate reduction therapy.

4568 Forty patients affected by various haematological malignancies who underwent high dose chemotherapy and autologous stem cell transplant (ASCT) were treated with Palifermin, this group was compared to 80 control subjects not assuming this drug. Controls were selected on the basis of being matched for length of neutropenia after ASCT and for Diagnosis. Primary end point was occurrence of “infections not CVC-related” (FUO/pneumonia/gram-negative bacteremia) and secondary end point was the “severe oral mucositis”. Patients and controls resulted to be comparable for many pre-transplant and transplant features. Patients treated with Palifermin displayed a lower rate of “infections not CVC-related” when compared to controls (25% versus 50%, P=0.01) and the protective effect of Palifermin on this outcome remained significant also in a multiple logistic regression model [odds ratio: 0.34, 95% CI: 0.12–0.92, P=0.03] adjusting for a series of potential confounders. The odds ratio of severe mucositis was 30% lower in Palifermin treated patients than in controls (odds ratio: 0.70, 95% CI: 0.33–1.51) but this difference did not attain the statistical significance (P=NS). A stratified analysis by conditioning therapy showed that in patients who received Palifermin after BEAM/BU-CY conditioning, the proportion of patients experiencing severe mucositis was significantly lower than that observed in controls (14% versus 56%, P=0.008) while no such difference was found in those who underwent HD-PAM conditioning (65% versus 56%, P=NS). This result indicates that the conditioning therapy modifies the effect of Palifermin on severe mucositis, a finding fully confirmed in a multiple logistic regression model (P for the effect modification=0.018). Palifermin treated patients had also lower severe gastrointestinal toxicity (12% versus 65%, P<0.001), lower morphine utilization (12% versus 40%, P<0.001), lower total parental nutrition (10% versus 71%, P<0.001) and lower PLT and RBC transfusions (P=0.04) when compared to controls. Average economical costs related to the sum of some resources (inpatient stay, TPN, systemic antifungal treatment and blood products transfusions) were lower in Palifermin treated patients than in controls (11.985 EUROs versus 15.717 EUROs, P=0.002) so that the economical saving in Palifermin treated patients (about 3.700 EUROs) fully compensated for the cost of this drug. Remarkably, in patients treated by “BEAM/BU-CY” conditioning therapy and receiving Palifermin, the overall costs (sum of the above mentioned resources and including also cost of the study drug) was lower in Palifermin treated group in respect to group of patients not treated. In fact, in BEAM/BU-CY stratum overall cost in group treated by Palifermin was 15990±2789 EUROs versus 19276±10946 EUROs in group treated by the same conditioning but not receiving Palifermin (P=0.11). In conclusion this controlled study shows that Palifermin, after ASCT using conditioning not containing TBI, significantly reduces rate of “infections not related to CVC” and ameliorates several indicators of resource consumption, without economical overburden. Disclosures: No relevant conflicts of interest to declare.