A case of brain abscess due to Trichoderma longibrachiatum in a leukemic patient with prolonged neutropenia is reported. Definitive cure was achieved after neurosurgical resection of the abscess and prolonged antifungal therapy. Trichoderma is a filamentous fungus species, which is only exceptionally pathogenic in humans. This genus and particularly the species Trichoderma longibrachiatum should be added to the growing list of fungi causing infection in immunocompromised patients.

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Non-obese diabetic (NOD) mice develop an autoimmune disease with a long prodromal period and constitute a model for investigating the prevention of human insulin-dependent diabetes mellitus. Since insulin injected prophylactically has been shown to reduce incidence of diabetes in NOD mice, we tested a new strategy consisting of prophylactic xenografts of porcine pancreatic islets immunoprotected in semipermeable hollow fibres. Female NOD mice were transplanted twice (at 60 and 180 days of age) with islet-containing or empty fibres. Within the group grafted with protected islets, the incidence of diabetes was reduced (37 vs 75%; p < 0.01), the onset of disease was delayed (p < 0.02), and the severity of lymphocytic inflammation of endogenous islets was reduced (p < 0.02). When already diabetic mice were not taken into account for analysis, blood glucose level was slightly lower in those grafted with islet-containing fibres (p < 0.04). Graft function was also evidenced by HPLC separation of porcine insulin in NOD sera. Histological and perifusion studies of fibres retrieved from recipients confirmed immunoprotection. During co-transfer, T splenocytes from mice grafted with islet-containing fibres were able to reduce the capacity of T cells from diabetic donors to adoptively transfer the disease (p < 0.01). Antigens for islet-cell autoantibodies (ICA) in pancreata from both groups were compared by immunofluorescence with the same ICA-positive human sera to ensure that differences were due to antigen quantitative changes. These antigens, which could serve as an index of a possibly more extensive antigen beta-cell rest, were decreased (p < 0.01) in mice grafted with protected islets. Reduction of diabetes and insulitis following early islet transplantation may thus be due to generation of cellular mechanisms that actively suppress disease, and possibly in part to a decrease in antigens which make beta cells less vulnerable to autoimmune aggression. These effects can be obtained with xenogeneic islets protected in hollow fibres, thereby eliminating the need for immunosuppression. Based on the concept of prophylactic insulin therapy, this form of insulin administration offers a controlled means of delivering insulin to meet the physiological needs of recipients.

2791 Introduction: Elderly mantle cell lymphoma (MCL) patients (pts) do not benefit from dose-intensive chemotherapy upfront.1 The GOELAMS group recently demonstrated that a regimen comprising Vincristine/Adriamycine/Dexamethasone plus Chlorambucil (VAD+C) was well tolerated, had a good efficacy/toxicity profile and induced similar PFS than R-CHOP (median PFS between 16 to 18 months2,3,4). Additionally, it has been shown that bortezomib (Velcade®), with or without Rituximab has efficacy in relapsed/refractory MCL patients5,6. These data prompted, our group to conducte a phase II prospective non randomized clinical trial evaluating the combination of Velcade plus Rituximab/Adriblastine/Dexamethasone/Chlorambucil (RiPAD+C) as a first line therapy for elderly MCL patients. Aims: To evaluate the overall response rate (ORR) and toxicity after 4 cycles of RiPAD+C regimen (main objective) and to evaluate prognostic factors for survival (secondary objective). Protocol: RiPAD+C : Rituximab 375 mg/m2 on d1 (and d8 for cycle 1); PS 341, Velcade® 1.3 mg/m2 on d1, 4, 8 and 11; Adriblastine 9mg/m2/d as a continuous infusion for 4 days; Dexamethasone 20 mgx2/d from d1 to d4; Chlorambucil 12 mg/d, d20 to d29. Repeat cycles every 35d. After 4 cycles, responding pts (Cheson 1999 criteria) received 2 additional cycles for a maximum of 6. Patients and methods: Inclusion criteria: All untreated elderly (65 to 80 years old) MCL patients (including blastoid forms) presenting with a stage II to IV disease with a good PS (ECOG<3) were eligible. Histologic samples were centrally reviewed and Ki67 expression was evaluated for each sample according to the European guidelines7. Results: Population: from June 2007 to December 2009, 39 pts were enrolled in the study with a majority of males (n=30). Median age at diagnosis was 72 years [65-80]. All patients had stage III/IV disease and PS was ≥2 in 5 cases (15%). Elevated serum LDH were observed in 47% of cases. According to the MIPI, 28 patients (80%) had an intermediate or high score. Eleven (30%) patients presented with a blastoid variant and Ki67 staining was superior to 30% in 12 cases (37%). Toxicity: A total of 195 courses have been performed. Fourteen hospitalization (median duration = 7 days [1 and 55]) due to toxicity were necessary involving 12 pts (34%). Seven pts (18%) experienced grade 3 peripheral neuropathy. ten (25%) pts required blood transfusions for a total of 8 red blood cells and 14 platelets transfusions. Response after 4 cycles: ORR was 80% (n=31) including 51% of CRs. Eight pts discontinued the treatment before reaching cycle 4, two of them for toxicity reasons. Six patients (15%) were refractory or in progression. Response after 6 cycles (n=25; 64%): ORR was 74% including 20 pts in CRs (59%). Survival: With a median follow-up of 24 months, 27 pts are still alive. Two pts died of toxicity (severe sepsis) and 10 pts progressed. The median PFS is 26 months and the median OS has not been reached yet. According to the MIPI score, no differences in PFS were between pts with low and int/high scores. Conversely, the recently described Goelams index2 stratified pts with a low score (normal LDH, Ki67≤26%, PS≤1, and no B symptoms) from patients with an int/high score (p=.055). Conclusion: The results of the current phase II trial indicate that the RiPAD+C regimen, integrating bortezomib, is feasible and well tolerated as a first line therapy in elderly MCL pts. Historical comparisons suggest that this regimen compares favourably to the classical R-CHOP regimen in terms of response rates and duration. Bibliography: 1 Romaguera JE et al, JCO 2005; 2 Gressin R et al., Haematological 2010; 3 Howard OM et al., JCO 2002; 4 Lenz G et al., Blood 2005; 5 Fisher RI et al., JCO 2006; 6 Goy A et al., JCO 2009; 7 Klapper W et al., Haematopathol 2009. Disclosures: Off Label Use: velcade is of label in France for the treatment of mantle cell lymphoma.