ALBERT

Description: Recombinant thrombin (rThrombin) is an active topical hemostat that is approved by the FDA as an aid to hemostasis. The safety, immunogenicity, and efficacy of rThrombin have been demonstrated in 1 Phase 1 study, 5 Phase 2 studies, and 1 randomized, double-blind Phase 3 study. No safety observations have been deemed clearly causally related to exposure to rThrombin; favorable immunologic response to rThrombin was observed in these trials. Treatment with thrombin derived from bovine sources has occasionally been associated with adverse events which appear to be related to the formation of antibodies against bovine thrombin and/or Factor V. A boxed product warning indicates that patients with antibodies to bovine thrombin preparations should not be re-exposed to these products. Secondary immune responses to bovine thrombin re-exposure may occur in patients with antibodies to bovine thrombin product. This Phase 3b open-label, single-group, multisite study was designed to evaluate the immunogenicity and safety of rThrombin among subjects at increased risk for having anti-bovine thrombin product antibodies as a result of prior surgery with a high likelihood of bovine thrombin exposure (N=209). Topical rThrombin was applied during a single spinal or vascular surgical procedure. Immunogenicity was evaluated by enzyme-linked immunosorbent assay at baseline and Day 29; safety measures were evaluated through Day 29. Subjects were eligible for participation if they had definite or highly likely prior exposure to bovine thrombin within the previous 3 years. Preliminary results from 162 subjects enrolled and evaluated as of the cut-off date (28 July 2008) are presented herein; complete study results will be available at the meeting. Of the subjects evaluated to date, 78 (48%) had definite prior exposure to bovine thrombin; prior exposure was highly likely for 85 subjects (52%) and unknown for 1 subject. At baseline, 139 subjects (86%) were seronegative and 23 (14%) were seropositive for anti-bovine thrombin product antibodies. Anti-rThrombin product antibodies did not develop through Day 29 post-treatment in any subject; thus, the rate of antibody formation to rThrombin was the same regardless of anti-bovine thrombin product antibody status. Of the 4 subjects who had anti-rThrombin product antibodies at baseline, none had a change in titer ≥1.0 unit at Day 29. Common adverse events (AEs; reported by ≥10% of subjects) were consistent with the post-surgical setting and with prior studies of rThrombin in these surgical populations. Common AEs included incision site pain, procedural pain, nausea, constipation, anemia, muscle spasms, hypotension, and pyrexia. Topical application of rThrombin was well tolerated, and there was no difference in the formation of antibodies to rThrombin at Day 29 in subjects with or without pre-existing antibodies to bovine thrombin product. The results from this study provide additional information about the immunologic safety of rThrombin and suggest that rThrombin can be safely applied as an aid to hemostasis in patients with pre-existing antibodies to bovine thrombin.

Description: Background: Invasive microbial infections remain a major cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) patients. Microbes residing in the GI tract are believed to be the source of mucosal barrier injury-associated blood stream infections (mBSI) in HSCT and cancer patients. Three host factors are critical for preventing microbial translocation from the gut: neutrophils, intact gut barrier function, and gut microbiota homeostasis. Currently there are no reliable biomarkers that can identify patients who will develop mBSIs. Objectives/Hypothesis: Since all HSCT patients develop severe neutropenia (ANC

Description: Abstract 1808 Background: Approximately 50% of the Multiple Myeloma (MM) cases are associated with hyperdiploidy (Hyperdiploid MM, HDMM), usually of the odd numbered chromosomes. The majority of the remaining patients with MM have translocations involving the immunoglobulin heavy chain (IgH) locus on chromosome 14q32 (Translocated MM, TMM).(Fonseca R, Leukemia 2009;23:2210-21) However, most of these estimates are from studies done in predominantly white populations. MM is approximately two fold more common in blacks, and results from the phase 3 study of lenalidomide and dexamethasone suggested that blacks may have better outcome. (Rajkumar SV, Lancet Oncol 2010;11(1):29-37) Goals: The purpose of this study was to determine the cytogenetic characteristics and outcome of MM in blacks, and to compare this with a similar population of white patients seen during the same time period. Methods: We studied African American and African patients with MM diagnosed from May 2002 through June 2010 at John H. Stroger, Jr. Hospital of Cook County (CC), Chicago, IL and comparable Caucasian population seen at Mayo Clinic (MC), Rochester, MN between these dates with available cytogenetic studies (karyotyping and/or fluorescent in situ hybridization (FISH) data) at diagnosis. The results between both populations were then compared. Results: 65 blacks (25 men and 40 women) and 490 Caucasians (290 men and 200 women) with MM were studied. Karyotyping was available in 98% of patients from both cohorts, and FISH was available for 35% and 64% of the CC and MC cohorts, respectively. A molecular classification was possible in 16 (25%) of the CC cohort (12 HDMM, 4 TMM) and 294 (60%) of the MC cohort (38% HDMM, 22% TMM). In the remaining patients, both tests were normal or showed changes not definitive for either IgH translocations or hyperdiploidy. At diagnosis, abnormal cytogenetics by karyotyping was present in 25/65 (38%) of the CC cohort and 154/479 (32%) of the MC cohort. The median overall survival (OS) from diagnosis for the CC and MC cohorts was similar at 64 months. The median OS was significantly shorter for those with an abnormal cytogenetics; 35 months vs. 65 months in the CC cohort (P0.03) and 49 months vs. not reached for the MC cohort (P 〈 0.01). OS was superior among patients in the CC cohort initially treated with an immunomodulatory agent (IMiD) containing regimen (65 months vs. 35 months for those receiving a bortezomib or other non-IMiD containing regimens (P=0.02; Figure 1). Similarly, in the MC cohort, patients receiving an IMiD based regimen had a superior OS (not reached vs. 42 months; P 〈 0.001). The use of immunomodulatory therapy did not differ across cytogenetic types. Conclusions: The current study suggests that IgH translocations were less frequently seen in blacks compared with what is typically reported in the literature. This may explain the relatively better survival reported in blacks compared with whites in recent trials. We found a significantly superior outcome in blacks treated initially with regimens containing immunomodulatory agents compared to other regimens. Disclosures: No relevant conflicts of interest to declare.