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Background and Aim Studies have reported association between red cell (RBC) transfusion (tx) and increased mortality and morbidity in cardiac surgery (CS). Conflicting data exist on whether universal RBC leucodepletion (ULD) reduces mortality and morbidity, particularly infection and intensive care unit (ICU) length of stay (LOS), in CS patients. RBC tx has also been independently associated with renal failure (RF) in CS, however mechanisms for this effect are unclear. An inflammatory basis has been postulated. No large studies have explored the potential benefit of ULD in reducing RF. We investigated whether introduction of ULD in Australia (July 2008) was associated with reduced in-hospital mortality, infection, new RF (NRF) and ICU LOS in a large cohort of CS patients. Methods All consecutive CS patients 18y and older at 6 hospitals between 2005 and 2010 were included. Clinical and outcome data were obtained from the Australian and New Zealand Society for Cardiac and Thoracic Surgeons Cardiac Surgery Database, which prospectively collects data on all CS patients. Laboratory results (pre-operative hemoglobin, platelet, coagulation profile and creatinine) and transfusion data were obtained from hospital laboratory information systems (LIS). Statistical analysis Tx was defined as ≥ 1 RBC within 48h of CS. Patients were categorized as having surgery pre- or post-ULD and as having received either exclusively LD, non-LD or mixed RBC. Logistic regression modeled the association between LD and mortality, infection and NRF. The association with LD was analyzed in two ways: whether surgery occurred pre- or post-ULD, and whether patients received LD or non-LD RBCs. To examine for trends over time, an equal number of non-tx patients were selected as ‘controls’, based on a propensity score for RBC tx. The relationship between LD and ICU LOS among survivors was explored using linear regression. Results 16,253 patients underwent CS in the study period. LIS data were available for 14,980 (92%), and of these, 8857 (59%) had surgery pre-ULD. RBC tx was given in 3799 (43%) pre-ULD, and 2525 (41%) post-ULD. Of the 6324 patients who were tx, 2794 (44%) received LD RBC, 2702 (43%) non-LD RBC and 828 (13%) received mixed LD and non-LD RBCs. In tx patients, there was no significant difference in mortality (136 [5.4%] vs. 240 [6.3%], p=0.125) or infection (310 [11.9%] vs. 510 [13.4%], p=0.080) post-ULD compared with pre-ULD, however there was a significant reduction in NRF (215 [8.5%] vs. 398 [10.5%], p=0.010). After adjusting for hospital, age, sex, co-morbidities, ejection fraction, pre-operative laboratory parameters, surgical history, type and urgency of procedure, pre-operative shock, medications, perfusion time, drain output in first 4 hours and number of RBC, there was no difference in mortality (OR 0.92, 95% CI 0.71-1.20, p=0.534) or infection (OR 0.96, 95% CI 0.81-1.15, p=0.671), however there was a difference in NRF post-ULD compared with pre-ULD (OR 0.77, 95% CI 0.64-0.94, p=0.011). When the analysis was repeated comparing those who received LD vs. non-LD RBC the results were similar, with no difference in mortality or infection, but a reduction in NRF (OR 0.80, 95% CI 0.65-0.98, p=0.035). In the non-tx controls, there was no significant difference in mortality (30 [1.2%] vs. 39 [1.0%], p=0.546), infection (139 [5.5%] vs. 231 [6.1%], p=0.338) or NRF (110 (4.4%] vs. 181 [4.8%], p=0.445) post-ULD compared with pre-ULD. After adjusting as above, there was no significant difference in mortality (OR 1.18, 95% CI 0.72-1.9, p=0.512), infection (OR 0.82, 95% CI 0.66-1.03, p=0.094) or NRF (OR 0.83, 95%CI 0.64-1.07, p=0.148) post-ULD compared with pre-ULD in non-tx pts. In the unadjusted linear regression, post-LD was associated with a small reduction in ICU LOS in transfused (41 vs. 44 h, p=0.034) and with a small increase in non-transfused (29 vs. 31 h, p Conclusions Introduction of ULD was associated with a reduction in NRF but not mortality, infection or ICU LOS in transfused CS pts. These findings support the potential role of inflammation as a contributor to acute RF in tx CS pts. ULD may be worth exploring prospectively as a possible strategy to reduce the incidence of NRF in CS, given its substantial morbidity and mortality. Disclosures: Phillips: CSL Behring: Research Funding. Wood:CSL Behring: Research Funding.

Abstract 4384 The management of musculoskeletal tumors has evolved markedly over the past 30 years, with improvements in surgical techniques, staging and chemotherapeutic advances delivering improved survival and functional outcomes, both in the setting of primary malignant bone tumors and in the palliation of tumors metastatic to bone. Advances in surgical technique as well as pre-operative chemotherapy has meant that most patients are now able to undergo limb-sparing surgery. Whilst clearly desirable to improve functional outcome, limb-sparing surgery is however more technically challenging and is associated with greater blood loss than amputation. There is a paucity of data concerning blood utilization in the setting of major musculoskeletal tumor surgery. We retrospectively analyzed a database containing 1322 consecutive surgeries in 1222 patients over a 14 year timeframe, performed at a quaternary referral center in Melbourne, Australia. The following factors were significantly associated with high blood utilization: Chordomas, sacral and pelvic tumors, lower starting haemoglobin, tumors >5cm in size and high American Society of Anesthesiologists (ASA) score. The ASA score also clearly correlated with 30 day mortality. Pre-operative planning in these patients is critical to ensure adequate blood supply, minimize wastage and optimize the patient's general health prior to surgery. As such, based on modeling from our data, we propose a maximum surgical blood order schedule based on the presence or absence of the above factors. Allogeneic blood transfusion, while a potentially life-saving intervention, is associated with major complications, including transmission of infectious agents and immunological complications. Longer-term, transfusion has been reported to result in immunomodulation and potentially a higher risk of tumor recurrence. Clearly, minimization of blood loss and avoidance of un-necessary transfusion is desirable. There is also a lack of data surrounding interventions designed to minimize blood loss in musculoskeletal tumor surgery, especially when compared to similar studies performed in major orthopedic surgery for benign conditions. These would be ideal targets for future randomized studies in the high-risk groups we have identified. Disclosures: No relevant conflicts of interest to declare.

Abstract 4385 The multiply alloimmunized patient poses a difficult predicament for clinicians, the hospital blood bank and duty hematologist. Whilst parallels may be drawn between patient blood management strategies used in the setting of blood refusal, others are unique to alloimmunization. There is limited literature guiding the management of the multiply alloimmunized patient requiring transfusion. We describe a 54-year-old lady who presented with symptomatic anaemia due to a delayed haemolytic transfusion reaction from an unidentifiable antibody. She had been transfused 2 units of red cells 13 days earlier in the setting of gastrointestinal bleeding. At this time she was found to have an anti- Fya antibody and was transfused with Rh matched, K negative, Fy(a-) and indirect anti-globulin test (IAT) cross-match compatible red cells. Her history included previous transfusions in the setting of bleeding, but no pregnancies. On admission hemoglobin (Hb) was 69 g/L [115 – 165], reticulocyte count 237× 109/L [20 – 100], bilirubin 33 μmol/L [T, encoding Gln581Leu and a silent 1671C>T, not affecting Ser557. These mutations are 2 out of the 3 mutations describing the LU- 13 genotype1. Our patient lacks the third mutation 1340C>T previously described. The patient's Hb dropped to 42 g/L and her treatment included bed-rest, intravenous iron, intramuscular vitamin B12, oral folate and erythropoietin. Whilst she had no active gastrointestinal bleeding she was given pantoprazole infusions and had a capsule endoscopy. She had a history of menorrhagia so was started on norethisterone and tranexamic acid to suppress menstrual loss. No first degree relatives were available for directed donation. She was transfused with 1 unit of IAT cross match compatible red cells together with 100mg prednisolone orally daily and 1g/kg intravenous immunoglobulin in an attempt to suppress immune haemolysis. She tolerated the transfusion well; however there was no increment in her Hb. Avoidance of unnecessary blood testing and pediatric collection tubes were used to reduce phlebotomy related loss. Over the next 10 days her Hb incremented without further transfusion to 78 g/L and had normalized by 4 weeks. Due to the need for future gastrointestinal surgery, on recovery of her Hb she had 5 autologous units of blood collected and frozen. Patient blood management strategies in the patient where the risk of potentially significant haemolytic reactions to transfusion is high must focus on minimizing blood loss, maximizing tissue oxygenation, promoting erythropoiesis and reducing metabolic needs. Approaches to lessen blood loss include early radiologic or surgical intervention to stop active bleeding, cessation or reversal of anticoagulants or aspirin and avoidance of medications or supplements associated with increased bleeding risk. Reducing phlebotomy-based blood loss includes minimizing the number of blood tests, using pediatric collection tubes and point of care devices. In our patient we investigated for ongoing bleeding sources, utilised proton pump inhibitors and used hormonal control for cessation of menstruation. Erythropoiesis was stimulated by the delivery of iron, folate, vitamin B12 and erythropoietin. Early investigation for associated coagulopathy or thrombocytopenia and early treatment with vitamin K, fresh frozen plasma and cryoprecipitate ensures that red cell volume is optimised. In a patient with multiple alloantibodies, the hospital blood bank should screen their inventory of donated red cells and consult with local and regional blood authorities. The blood typing of family members may allow for identification of potential donors. In the acute setting with an unstable haemorrhaging patient, the decision to transfuse the least incompatible blood may need to be considered. Long-term management plans may include autologous unit collection and identification of alloantibodies at a molecular level. Disclosures: No relevant conflicts of interest to declare.

Abstract 3311 Background Hemorrhage from disease processes or their therapy commonly complicates the course of patients with malignancies. Recombinant activated factor VII (rFVIIa) was developed for prevention or treatment of bleeding in hemophilia patients who have factor inhibitors, but may also have a role in enhancing coagulation and augmenting conventional therapies in refractory bleeding. However, outcomes are not defined for this indication, and randomized studies are challenging. We explored the safety and efficacy of rFVIIa in the treatment of hemorrhage associated with malignancy or stem cell transplantation (SCT) using prospective clinical registry data. Methods The Australia and New Zealand Haemostasis Registry (ANZHR) documented all rFVIIa use in non-hemophilia patients in both countries. More than 90 institutions participated in its operation from 2000 to 2009, capturing an estimated 85% of use in these countries. Participating institutions obtained approval from local institutional review boards to provide de-identified data. They were required to report all usage to limit bias and registry data were audited regularly. We identified episodes of rFVIIa use where the primary diagnosis at the time of hemorrhage was a malignancy or SCT. Response to rFVIIa reported by the treating clinician, transfusion requirements, adverse events and 28 day survival were analyzed. Logistic regression and multiple linear regression models were used to identify factors associated with response. Results Of 3446 episodes reported to ANZHR, 362 eligible episodes were identified in 325 patients (10.5% the total). Median patient age was 56 years (IQR 39–67); 205 (63%) were male. Episodes were reported from 51 institutions (57% of participating), median 5 (IQR 3–8) per institution. Primary diagnosis was hematological in 173 cases (48%); non-hematological malignancy in 189 (52%). 321 (88.6%) were receiving disease-directed therapy (initial therapy in 200 [55% of the total], 19 [5%] supportive care, unreported in 22 [6%]). Intent of care was curative in 218 (60%), palliative in 122 (34%), 22 (6%) unreported. 33 (9.1%) were undergoing allogeneic SCT and 5 (1.4%) autologous SCT. Primary sites of bleeding were gastrointestinal in 165 (46%), pulmonary 47 (13%), intracranial 36 (10%), genitourinary 34 (9%), hepatic 28 (8%), others 52 (14%). Causes of bleeding were 116 (34%) surgical (including resection of tumor or metastases), disease-induced coagulopathy 48 (14%), disease invasion 62 (18%), mucositis (including graft-versus-host disease) 53 (15%), others 65 (19%); 6 (2%) received rFVIIa prophylactically prior to procedures. In 255 episodes (70%) a single dose of rFVIIa only was administered. Median dose was 90μg/kg (IQR 77–100). Prior to administration median (IQR) hemoglobin was 82 g/L (69–93); platelet count 82 × 109/L (43–127), fibrinogen 2.1 g/L (1.4–3.1), INR 1.4 (1.2–1.8), pH 7.3 (7.2–7.4), temperature 36.7°C (36.0–37.1), and patients had received 5 (2–12) units red cells, 2 (0–4) platelet doses, 4 (0–8) plasma units, and 0 (0–8) cryoprecipitate doses. Bleeding stopped or decreased in 175 (60%) of cases where response was reported (prophylactic cases were excluded from response assessment). Transfusion requirements fell to 2 (0–4) red cells, 0 (0–2) platelets, 0 (0–3) plasma, and 0 (0–8) cryoprecipitate following the first dose. Response decreased with low pH in univariate analysis (p=0.014). In multivariate analysis, low pH and hematological malignancy were independent predictors of poor response (p=0.001). 18 patients (5.5%) had thromboembolic events reported within 28 days of administration. 202 patients (57%) survived to 28 days. Survival was significantly higher in rFVIIa responders (71% vs 38% p Conclusions This is the first comprehensive exploration of rFVIIa in hemorrhage associated with malignancy. Usage in this setting was higher than anticipated. Reported efficacy and safety were promising in this heterogeneous group with severe refractory bleeding and elevated baseline risk of thrombosis. Clinician-reported bleeding response was supported by reduced transfusion requirements and survival benefit. Response was associated with pH and type of malignancy, suggesting that these factors may assist in patient selection. Use of rFVIIa may be an effective adjunct to conventional therapies in carefully selected cancer patients with refractory hemorrhage. Disclosures: Off Label Use: Recombinant Activated Factor VII, for bleeding associated with malignancy.

Abstract 3158 Poster Board III-95 Background Previous studies have demonstrated significant variation in red cell transfusion in cardiac surgery. Allogeneic red cell transfusion has been reported as associated with adverse post-operative outcomes in this setting, whilst there is conflicting evidence on potential adverse effects of platelets. We investigated the variation in transfusion practice (including red cell, platelets and plasma transfusion) across six large cardiac surgery centres and whether peri-operative transfusion was independently associated with clinical outcomes. Methods Data were prospectively collected on 9363 cardiac surgery patients at six major Australian hospitals from January 2005 to December 2008 through the Australasian Society of Cardiac and Thoracic Surgeons (ASCTS) Cardiac Surgery Database. The independent association of transfusion (including red cells, platelets and plasma) with clinical outcomes was determined by stepwise logistic regression analysis. Patient factors (including co-morbidities and medication use such as anticoagulants and anti-platelet agents) and surgical factors (including type of procedure, previous cardiothoracic intervention, urgency of surgery, cardiopulmonary bypass time, cross-clamp time, return to theatre and other peri-operative complications) were included in the analysis. Results Procedure types were: coronary artery bypass graft (CABG) surgery in 60%, valve surgery in 14%, CABG and valve in 10% and other procedure in 16%. There was significant variation in transfusion of all blood components between the six hospitals, which was not accounted for by patient or surgery related factors. The adjusted odds ratio (OR) for the risk of receiving a transfusion of red cells varied between the hospitals from 0.22 to 1.98, for platelets from 0.39 to 3.3 and for plasma from 0.27 to 2.0. Transfusion of red cells, platelets and plasma were each associated with all outcome measures. In multiple logistic regression analysis, red cell transfusion was independently associated with multi-system failure (OR, 2.97; 95% confidence interval [CI], 1.41 - 6.28; p = 0.004), peri-operative myocardial infarction (OR, 2.63; 95% CI, 1.45 - 4.77; p = 0.001), stroke (OR, 1.76; 95% CI, 1.13 - 2.72; p = 0.012), prolonged ventilation (OR, 2.6; 95% CI, 2.19 - 3.06; p < 0.001), pulmonary embolism (OR, 4.29; 95% CI, 1.4 - 13.16; p = 0.011), pneumonia (OR, 2.12; 95% CI, 1.8 - 2.72, p < 0.001) and septicaemia (OR, 2.29; 95% CI, 1.31 - 4.0; p = 0.004). Platelet transfusion was independently associated with multi-system failure (OR, 2.17; 95% CI, 1.3 - 3.63; p = 0.003) and pneumonia (OR, 1.25; 95% CI, 1.02 - 1.52; p = 0.03). Plasma transfusion was independently associated with in-hospital (OR, 2.46; 95% CI, 1.82 - 3.32; p < 0.001) and 30 day mortality (OR, 2.2; 95% CI, 1.61 - 2.99; p < 0.001), multi-system failure (OR, 1.97; 95% CI, 1.18-3.31; p = 0.010), prolonged ventilation (OR, 1.81; 95% CI, 1.55 - 2.13; p < 0.001) and septicaemia (OR, 1.83; 95% CI, 1.17 -2.85; p = 0.008). Conclusion There was significant variation in transfusion practice for red cells, platelets and plasma across these six major hospitals that was not accounted for by patient or surgery related factors. Peri-operative transfusions of red cells, platelets and plasma, after adjusting for established clinical risk factors, were each independently associated with an increased risk of adverse events. These findings from a large cohort of patients are in keeping with previous reports of adverse events associated with red cell transfusion in cardiac surgery and support the need for further research into the effects of transfusion on patient outcomes. An improved understanding of factors contributing to the significant variation in transfusion practice is also required as this may have important implications for patient outcomes. Disclosures No relevant conflicts of interest to declare.

Treatment of various haematological malignancies such as chronic lymphocytic leukaemia (CLL) with alkylating drugs (e.g. chlorambucil, CLB) fails to extinguish the leukaemic clone and often results in chemo-resistance. A possible mechanism of drug resistance in CLL B cells is p53 inactivation. The resistance of cells to standard chemotherapy may be ameliorated by agents that alter the chromatin remodelling processes, DNA methylation and histone acetylation (e.g. sodium butyrate, NaBu). We used the HL-60 cell line (which carries a non-functional p53 protein) as a cell model for resistant CLL B cells and determined the sensitivity of HL-60 cells to a range of concentrations of CLB (5μM,10μM and 20μM) and NaBu (0.5mM, 1mM and 2mM) by tetrazolium salt-based proliferation assays of cells incubated with the drugs over 4 days (days 0, 1, 2 and 3). Cells were resistant to 5μM CLB until day 3 where 56% of cells were killed. 10μM and 20μM CLB had very similar effects (p>0.05) with both treatments killing 83.2% and 87.3% respectively of cells by the end of the incubation. The cell death induced by NaBu was both time- and dose-dependent, with 2mM NaBu being the most effective treatment, while 0.5mM NaBu did not result in significant cell death (p>0.05). To investigate if the treatment of HL-60 cells with both drugs would enhance or have an additive killing effect on the cells, we tested combined treatment involving a series of lower drug concentrations of each of the two drugs (5μM/10μM CLB ± 0.2mM/0.5mM/1mM). All combined treatments using 5μM CLB were more effective in cell killing than when the cells were treated singly with CLB or NaBu (p0.05). In conclusion, combined treatment involving NaBu increased the cytotoxic effect of low concentrations of CLB in p53-inactivated cells, implying the potential benefit of chromatin modifying agents in cytotoxic therapy. Further studies including the use of a wider range of concentrations of CLB with NaBu or other chromatin modifying agents are underway to investigate possible synergism in the killing of HL-60 cells by these agents.

Optimal management of intercurrent hematological malignancy in patients with HIV, in particular the feasibility of allogeneic peripheral blood stem cell transplantation (PSCT), remains to be defined. We present our experience with allogeneic transplantation in a series of three patients with HIV. The first patient is a 38 yo man with secondary myelodysplasia in transformation to acute myeloid leukemia. He had had no AIDS-defining illnesses, and was maintained on second-line anti-retroviral therapy of Stavudine, Lamivudine and Tenofovir with an undetectable HIV viral load and CD4 count 58 cells/μL. He received a HLA-identical PSCT, conditioned with cyclophosphamide 60 mg/m2 and total body irradiation (TBI) 13.2 Gy in 6 fractions with standard graft-versus host disease (GVHD) and infective prophylaxis. Transplantation was complicated by severe BK-virus associated hemorrhagic cystitis and prolonged neutropenia with sepsis necessitating temporary withdrawal of anti-retrovirals. Engraftment occurred at day 48, and bone marrow aspirate (BMA) confirmed remission. Anti-retroviral therapy was re-introduced 12 months post-transplantation in response to a rising HIV viral load. He subsequently developed progressive renal impairment due to post-transplant glomerulopathy, but had no late infective complications and is otherwise well and in remission 21 months post-transplantation with HIV viral load 150 copies/mL and CD4 count 181 cells/μL. The second patient was a 41 yo man with multiply-relapsed acute myeloid leukemia in third complete remission. He had no AIDS-defining illnesses and was maintained on fifth-line anti-retroviral regimen of Emtricitabine, Tenofovir, and Fosamprenavir with an undetectable viral load and CD4 count 275 cells/μL. He received an HLA-Identical sibling PSCT, conditioned as above, with additional anti-microbial prophylaxis with Entecavir for HBV; Azithromycin for MAC and Ciprofloxacin for a previous Rhodococcal pulmonary infection. Transplantation was complicated by neutropenic sepsis, pericarditis, and grade 2 cutaneous GVHD. Engraftment occurred day 21; BMA confirmed remission. He remained well with no further infective complications until day 67, when he presented with drug resistant Pseudomonal sepsis, multi-organ failure and succumbed day 78. The third patient was a 24 yo man with multiply-relapsed T-cell acute lymphoblastic leukaemia in second complete remission without prior AIDS-defining illnesses, maintained on second-line anti-retroviral regimen of Tenofovir, Ritonavir, and Fosamprenavir, with an undetectable HIV viral load and CD4 count 204 cells/μL. He received an HLA-identical sibling PSCT conditioned with etoposide 60 mg/m2 and TBI 13.2 Gy in 6 fractions, with extended anti-microbial prophylaxis. This was complicated by neutropenic dental infection and grade 2 cutaneous GVHD, treated with steroid therapy. Engraftment occurred day 25; BMA confirmed remission. There were no late complications and he maintained an undetectable HIV viral load and CD4 counts >200 copies/mL. At day 101 he relapsed, was treated with palliative intent, and died day 105. This series illustrates that allogeneic transplantation is a feasible therapeutic modality for high-grade hematological malignancies in carefully selected patients. Careful optimization of HIV control, and preventive management of infective complications and drug toxicity are critical to successful outcomes.

Passenger lymphocyte syndrome (PLS) is rare following solid organ transplantation. We describe 3 transplant recipients who developed severe hemolysis after receiving organs from a single donor with multiple red cell (RC) alloantibodies. The donor was a 54 y.o. male, blood group O Rh(D) negative (rr) with a positive antibody screen due to anti-D, anti-C and anti-k. His Cellano negative and RC alloantibody status was well characterized antemortem, given that he was a rare RC phenotype donor for the Australian Red Cross Blood Service (ARCBS). The lungs and the liver were offered for organ donation. The right single lung recipient was a 61 y.o. male with emphysema (blood group O Rh(D) positive [R2r]). From post transplant day (PTD) 0 to 10 his hemoglobin (Hb) fell from 126g/L to 69g/L without bleeding and with elevated hemolytic markers. A positive direct antiglobulin test (DAT) due to IgG was noted and anti-D eluted. Management included increased immunosuppression and transfusion of 2 RC units (rr, k positive). Ongoing hemolysis required a second transfusion at PTD 24. To facilitate tapering of corticosteroids, intravenous immunoglobulin (IVIG; 2g/kg in divided doses) was administered. The patient subsequently stabilized and 3 months post-transplant has mild compensated hemolysis with persisting anti-D. The left single lung recipient was a 59 y.o. female with emphysema (blood group O Rh(D) positive [R1r]). From PTD 0 to 10, Hb fell from 91g/L to 73g/L with elevated hemolytic markers. The antibody screen and elution demonstrated anti-D, and she was transfused with 2 RC units (rr, k positive). Three months post transplant she has ongoing evidence of mild compensated hemolysis with persisting anti-D. The liver recipient was a 45 y.o. male with Hepatitis B (blood group B Rh(D) positive [R1R1]). From PTD 0 to 13 Hb fell from 102g/L to 64g/L without bleeding. The DAT was positive (IgG) at day 4. Anti-D+B+C were detected in the plasma and anti-C+D+k+B were found in eluates. He was managed with increased immunosuppression and transfusion of 2 RC units (rr, k negative). Fresh Cellano negative units were accessed through the ARCBS rare RC register. The patient has subsequently also stabilized, despite ongoing seropositivity for anti-D (but not anti-k). These cases highlight the potential for severe hemolysis due to PLS following solid organ transplant. This is the first apparent description of PLS where anti-k has been implicated, with significant hemolysis in all recipients of organs from the same donor. We conclude that the identification of donor RC alloantibodies at the time of transplant should prompt close surveillance for development of PLS. Consideration of strategies to ameliorate hemolysis, such as early use of IVIG, is suggested. Where an antibody to a high incidence antigen (such as Cellano) is detected, early notification of central blood bank services may facilitate call up of phenotyped donors and provision of rare units.

Chronic Lymphocytic Leukaemia (CLL) is a lymphoproliferative disorder in which leukaemic B cells are arrested in the G0/G1 phase of the cell cycle, resulting in their prolonged lifespan. The clinical course of CLL is highly variable with survival ranging from a few months to decades. Thus, a good prognostic tool is needed to help predict the course of the disease. The pathogenesis of CLL is unknown but it has been associated with the “escape” of B cells from apoptosis, possibly due to overexpression of anti-apoptotic genes and downregulation of pro-apoptotic genes. The expression of these genes is influenced by alterations in chromatin structure through a change in DNA methylation (chromatin remodelling) mediated by multi-protein complexes. The Vitamin D receptor (VDR), which forms part of one such chromatin remodelling complex, has been shown to be linked to the susceptibility to and outcome of other malignancies (e.g. prostate cancer). We hypothesised that VDR polymorphisms (FokI, TaqI, BsmI and ApaI) may be linked to CLL pathogenesis and/or might be a marker of CLL progression, given the immunomodulatory actions of Vitamin D. The genotypes of 34 patients with CLL were determined by either allele-specific PCR (FokI) or PCR/restriction digestion analysis (TaqI, BsmI and ApaI). Clinical data including disease stage (Rai), other prognostic markers (e.g. lymphocyte doubling time) and therapy status were recorded. Statistical analysis including Wilcoxon, Chi-square and Spearman correlation tests were performed. Initial analysis-to-date has not shown significant difference in allelic distribution between CLL patients and a healthy control population. There was no statistically significant association between the 4 VDR polymorphisms and the clinical parameters of CLL (all p>0.05). A larger cohort of CLL patients is currently under study to determine any such potential correlation.