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Lipoproteins and vascular factors may play roles in the development of Alzheimer's disease (AD) and/or vascular dementia (VaD). In this study, odd ratios (ORs) and 95% confidence intervals (CIs) for apolipoprotein E (APOE), angiotensin-converting enzyme (ACE), and kallikrein (KLK1) polymorphisms were computed to test their association with the disease by a case-control study. The risk of AD was significantly increased for individuals with APOE varepsilon4 allele (OR = 3.73, 95% CI = 2.38-5.98). The risk of AD was also significant for people with ACE DD genotype, D allele, or T-D haplotype [OR (95% CI) = 4.29 (1.96-10.23), 1.90 (1.35-2.70), or 2.91 (1.71-5.10), respectively]. The above association between ACE-VaD was also strong (p = 0.0012, 0.0050, 0.0007, respectively). Reporter constructs containing the -240 A or T allele displayed similar transcriptional activity in both HEK-293 and IMR-32 cells. Thus, another putative pathogenic marker that is linked with the Alu D allele might affect the risk of AD and VaD in Taiwan.

Autologous blood donors (ABDs) have been reported to have favorable attitudes toward returning as homologous blood donors (HBDs), but the frequency of return has not been well documented. ABDs eligible by history to be HBDs were followed at one blood center: 255 donating for elective surgery and 234 donating during pregnancy were followed for an average of 18 months and 20 months, respectively, from time of eligibility after surgery or postpartum. Male ABDs had a higher rate of return as HBDs, as 34 percent (21/62) returned to donate an average of 3 units, whereas 13 percent (56/427) of female ABDs returned as HBDs to donate an average of 2 units. Although a history of donation was associated with a higher rate of return (30%, 34/113), 11 percent (43/376) of ABDs with no history as HBDs returned to donate homologous units, despite having been recruited less frequently than prior HBDs. Overall, all male ABDs and female ABDs with an HBD history returned most frequently. The extra effort required for an autologous donor program may result in the recruitment of new donors into the HBD pool.

Adults with acute leukaemia and abnormalities of chromosome 11q23 have a poor prognosis when treated with conventional chemotherapy. To determine whether more intensive therapy can improve outcome for patients with this karyotypic finding, a retrospective analysis of all patients with acute leukaemia and 11q23 abnormalities treated at our centre was performed. 12 patients were treated with conventional chemotherapy alone (CC); 20 patients received high-dose chemo/radiotherapy (HDCT) with autologous (seven patients) or allogeneic (13 patients) bone marrow transplantation (BMT). The treatment-related mortality was 25% [95% Confidence Interval (CI) 7-69%] for the CC group and 46% (CI 25-73%) for the BMT group (P = 0.69). Cumulative risk of leukaemia progression was 89% (CI 61-100%) in the CC patients and 38% (CI 12-69%) in the BMT patients (P = 0.001). The 2-year event-free survival for patients treated with CC was 8% (CI 0-31%) and for patients receiving HDCT and BMT was 34% (CI 14-54%) (P = 0.03). These results confirm that conventional chemotherapy is rarely curative for adults with acute leukaemia and 11q23 abnormalities but that HDCT with BMT can result in long-term survival in a significant proportion of patients.

Allogeneic bone marrow transplantation (BMT) is the only curative therapy available for patients with myelodysplastic syndrome (MDS). In an attempt to identify prognostic factors influencing outcome, we collected data retrospectively on 60 consecutive adult patients who had undergone BMT at our center for primary MDS or acute myelogenous leukemia evolving from preexisting primary MDS (sAML). Patients were divided into subgroups according to cytogenetic abnormalities based on a recently described International MDS Workshop categorization system. The 7-year actuarial event-free survival (EFS), relapse rate, and nonrelapse mortality (NRM) for all patients were 29% (95% confidence interval [CI], 16% to 43%), 42% (CI, 24% to 67%), and 50% (CI, 37% to 64%), respectively. The EFS for the good-, intermediate-, and poor-risk cytogenetic subgroups were 51% (CI, 30% to 69%), 40% (CI, 16% to 63%), and 6% (CI, 0% to 24%), respectively (P = .003). The corresponding actuarial relapse rates were 19% (CI, 6% to 49%), 12% (CI, 2% to 61%), and 82% (CI, 48% to 99%), respectively (P = . 002) with no difference in NRM between the subgroups. Univariate analysis showed cytogenetic category, French-American-British (FAB) subtype, and graft-versus-host disease (GVHD) prophylaxis used to be predictive of relapse and EFS. In multivariate analysis, only the cytogenetic category was predictive of EFS, with the relative risk of treatment failure for the good-, intermediate-, and poor-risk cytogenetic subgroups being 1.0, 1.5, and 3.5, respectively (P = . 004). For adults with primary MDS and sAML, even after BMT, poor-risk cytogenetics are predictive of an unfavorable outcome; novel treatment strategies will be required to improve results with allogeneic BMT in this patient population.

Thirty-three cats under intraperitoneal chloralose (40 mg/kg) and urethane (400 mg/kg) anesthesia were used to explore the effect of microinjections (100 nl) of carbachol (CCh, 0.5 M), a cholinergic analogue, glycine (Gly, 1 M) and gamma aminobutyric acid (GABA, 0.4 M) on the cardiovascular-reactive sites in the pontomedulla that responded to microinjection of monosodium glutamate (Glu, 0.25 M, 100 nl) resulting in changes of systemic arterial pressure (SAP). Brain sites under exploration included gigantocellular tegmental field and lateral tegmental field (FTG-FTL), the dorsomedial (DM) and ventrolateral (VLM) medulla which produced pressor responses; caudal VLM (CVLM) and paramedian reticular nucleus (PRN) which produced depressor responses. It was found that CCh produced significant fall of SAP in DM and VLM while the rise of SAP in the same site by Glu. CCh produced SAP decrease in CVLM similar to Glu. GABA significantly caused a slight to moderate increase of SAP in FTG-FTL, DM and VLM, and decrease of SAP in CVLM, all in direction similar to that of Glu. Gly produced significant and marked increase of SAP in DM and VLM similar to Glu both in magnitude and duration. Gly produced increase of SAP in CVLM but the fall of SAP by Glu. PRN was relatively non-reactive except a few microinjections of CCh which produced hypotension. In conclusion, the cardiovascular-reactive sites in the pontomedulla that respond to Glu may also react to other chemicals or neurotransmitters. It is highly possible that multiple receptors of different nature co-exist in neurons of some cardiovascular regions in the pontomedulla.

7102 Background: Sorror et al. has identified HCT-CI as a valid scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival after allogeniec HCT. We recently reported on the validity of HCT-CI in predicting morbidity outcomes after AHCT for lymphoma (BBMT in press). High HCT-CI score predicted for prolonged hospitalization and high incidence of hospital re-admission after AHCT. The objective of this study is to evaluate the impact of HCT-CI on mortality risk after AHCT. Methods: We included pts above age of 40 with advanced HL or NHL, who underwent AHCT in our institution between 01/98 & 05/06. Median follow up was 29.4 mo. Pts were assigned scores based on the HCT-CI. Defenition of comorbidities were recently reported (Kassar et al, BBMT in press). Results: 80 pts were included (NHL: 74, HL: 6). 61 pts were male. Median age was 56 years (42–76). Comorbidities (points, prevalence%): mild hepatic (1,14), cardiac (1,15), cerebrovascular (1,4), arrhythmia (1,9), moderate pulmonary (2,11), severe pulmonary (3,8), rheumatologic (2,5), DM (1,23), inflammatory bowel disease (1,3), psychiatric (1,11), infection (1,6), obesity (1,11), and renal (2,1). Median HCT-CI was 1 (0: 37 %, 1: 26%, 2–7: 37%). 22 pts died: 15 from relapse and 7 from non relapse mortality (NRM) causes. Cumulative day-100 NRM and 1-year NRM rates are: 1.3% and 4%, respectively. Pts were categorized into 2 groups: low-risk (scores of 0–1) and high-risk (scores 2–7). Using Cox Regression model and adjusting for age and histology, low-risk group had a significantly better OS (1 wk-58.6 mo, median 34.1 mo) compared to high-risk group (5 days-23.6 mo, median 6 mo) (HR: 3.73, p = .01, 95% CI 1.32, 10.54). 1-year OS rate was 75% vs. 25%, respectively (p=.04). Conclusion: HCT-CI is a valid scoring of pre-transplant comorbidities that predicted mortality after AHCT for pts with lymphoma. The physiologic burden of comorbidities is likely to impact the tolerance to AHCT or to other therapies administered upon relapse after transplant. HCT-CI can serve as important tool for both the transplant administrator when planning for resources allocation and clinical trials, and for pts during pre-transplant evaluation and counseling. No significant financial relationships to disclose.

13060 Background: Multiple myeloma (MM) is the most prevalent plasma cell neoplasm and is characterized by the infiltration of the bone marrow by terminally differentiated B lymphocytes. Although novel drugs have recently been introduced, the disease remains incurable. No therapeutic antibody is as yet available for treatment of MM. One of the key molecules involved in multiple myeloma (MM) tumor progression is syndecan-1, a cell surface heparan sulfate (HS) proteoglycan expressed on both MM cells and normal plasma cells. Syndecan-1 regulates cell interactions with soluble molecules and the extracellular matrix through its heparan sulfate chains. These chains allow it to bind multiple growth factors such as Fibroblast Growth Factor type 2 (FGF-2), WNT, Hepatocyte Growth Factor (HGF), midkine, all of which promote survival and metastasis of MM cells. In addition, syndecan-1 on MM cells binds and internalizes osteoprotegerin, the RANKL antagonist, through its HS chains and depletes it from the bone marrow milieu, which triggers osteoclastogenesis. Methods: Using the phage display technique, we have generated a panel of MM-specific human antibody variable fragments (scFvs) against the MM cell line RPMI-8226. These scFvs were tested against a variety of cell lines and primary normal bone marrow or myeloma cells. The biochemical identity of the targeted antigens was determined. Results: Two of the selected scFvs, D4A4 and D6B10, reacted against heparan sulfate motifs that were highly expressed in MM cell lines and patient MM cells but absent (scFv D6B10) or poorly expressed (scFv D4A4) in normal plasma cells. Binding of scFv D6B10 to MM heparan sulfate chains required NS sulfation, 6-O-sulfation and, to a lesser extent, 2-O-sulfation. Additional experiments indicated that FGF-2, midkine and osteoprotegerin competed with scFv D6B10 for binding to HS. Conclusions: This study indicates that the structure of syndecan-1-associated HS is altered in MM cells and may influence its capacity to bind to growth factors and promote tumor progression. Human therapeutic antibodies derived from scFvs D4A4 and D6B10 may be useful for immune targeting of MM cells and interfering with pro-survival signaling pathways. No significant financial relationships to disclose.