SummaryHeparin-induced thrombocytopenia (HIT), a prothrombotic complication of heparin therapy, can lead to serious thromboembolic events and cause significant morbidity and mortality. We aim to study the prevalence of HIT in the transplant population at our institute. This is a retrospective, single-center study which looked into the transplant database over a 25-year period. In patients with clinical suspicion of HIT, the 4T score was used, and laboratory tests such as ELISA HIT antibody and functional serotonin release assay, along with clinical manifestation of thromboembolic events were reviewed. Medical records of 2800 patients who underwent transplantation from January 1985 to December 2010 were reviewed. HIT antibody assay was performed in 262 patients from this group in which HIT was suspected. Of these, only 48 patients were HIT antibody positive along with moderate to high 4T score. The mean 4T score was 6.75 AE 1.4. Thrombotic complications were seen in 11 patients, with the highest in cardiac transplant recipients. Direct thrombin inhibitor (DTI) therapy was used in only eight patients who had thrombotic event. No other complications or mortality was reported in any of the HIT antibody-positive transplant patients. To our knowledge, this is the first study of its kind that has shown very low incidence of HIT in the transplant population except for in cardiac transplant recipients.

A middle-aged man diagnosed with a drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, secondary to phenytoin use, subsequently developed thrombotic thrombocytopaenic purpura. The patient improved with steroids and plasmapheresis. Their diagnosis can be challenging, and an early recognition and treatment are critical owing to their high mortality rates. Both diseases are thought to be of an autoimmune origin, and a potential relationship between them led to the consideration of the DRESS syndrome as an aetiology for thrombotic thrombocytopaenic purpura in this case. We concluded that two possibilities exist: some type of antibody developed during the clinical presentation of DRESS syndrome and subsequently resulted in an inhibition of a disintegrin and metalloproteinase with a thrombospondin type-1 motif, member 13 (ADAMTS13) leading to thrombotic thrombocytopaenic purpura, or perhaps this patient's autoimmune predisposition to thrombotic thrombocytopaenic purpura contributed to the drug reaction.

7531 Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults and has a heterogenous presentation. CLL is known to shape the immune response to survive. Studying these processes will help gauge the potential success of immunotherapy and point to therapeutic targets. Methods: We used our Search, Tag, Analyze, Resource platform to meta-analyze patient samples from Gene Expression Omnibus. We tagged peripheral B cells from 741 CLL patients and peripheral B cell samples from 150 healthy donors as a control. We also tagged and compared B cell samples from 84 CLL progressors to 91 patients with stable CLL. Lastly, we tagged peripheral T cells from 70 CLL patients and T cells from 35 healthy donors as a control. We then analyzed the signature in Ingenuity Pathway Analysis. Results: Analysis of CLL cell samples identified T cell exhaustion signaling as our top canonical pathway. IL2, IL5, and TGFB1 were top upstream regulators. We found upregulation of PDL1, CTLA4, and Lag3, known markers for immunosuppressive B cells. FMOD, which sequesters TGFB, was also upregulated along with molecules that modulate BCR signaling such as MIR155HG. EBF1, required for B cell differentiation, and the co-stimulatory molecule CD80 were downregulated. Analysis of progressing CLL versus stable CLL highlighted metabolic changes. S-adenosyl-L-methionine biosynthesis, methionine degradation to homocysteine, cysteine biosynthesis, and acetate conversion to acetyl-CoA were top canonical pathways. No difference was seen in PDL1, CTLA4, and Lag3 expression but EBF1 was upregulated. Lastly, our T cell analysis demonstrated NFAT in regulation of the immune response as the top canonical pathway. Conclusions: Our results reinforce the promise immunotherapy can have in treatment of CLL and suggests more aggressive cases of CLL are a function of metabolic changes as opposed to differences in immune escape. We also suggest a role of NFAT in T cell exhaustion in the context of CLL.

3320 Objective: Heparin induced thrombocytopenia (HIT), a prothrombotic complication of heparin therapy, can lead to serious thromboembolic events and cause significant morbidity and mortality. Its occurrence has never been studies in transplant patients, where use of heparin products is very common. We aim to study its prevalence in the transplant population at our institute. Methods: This is a retrospective cohort, single center study which looked into the clinical and laboratory database of all the patients that has undergone any kind of transplant at our institution over a period of 25 years (January 1985 - December 2010). In patients with clinical suspicious of HIT, a pre-test probability was calculated using the 4T scoring system. Results of the laboratory test like the ELISA HIT antibody (HIT ab) test and the functional serotonin release assay test (SRA) along with clinical manifestation of skin necrosis or thromboembolic events were reviewed. Results: Medical records of 2800 patients that has undergone transplant from January 1985- December 2010 were reviewed. HIT antibody assay was performed in 262 patients in which HIT was suspected. Of these, only 48 (18%) patients (mean age 57 ± 11 years, 71% women) had HIT ab positive, 9 were pre transplant recipient and remaining 39 were post transplant recipients. Baseline characteristics of the transplant population are illustrated in Table.1. Confirmatory test, SRA was performed in 8 HIT antibody positive patients, of whom only 4 were positive. The mean 4T score in HIT suspected patients was 3.7 ±1.3, while the score in HIT ab positive patients was 4.2 ± 1.2. Thrombotic complications were seen in 11(0.4%) patients, with the highest incidence rate of 1% in heart transplant recipients. No transplant patient had skin manifestations. Direct Thrombin inhibitor (DTI) was used only in 5 patients who had thrombotic events. No other complication or mortality was reported in any of the HIT ab positive transplant patients. Conclusion: To our knowledge, this is the first study of its kind that has shown very low incidence of HIT in transplant population. In conclusion, transplant patients can safely undergo any type of organ transplant, without having any peri or post operative complications or immediate mortality related to HIT. Disclosures: No relevant conflicts of interest to declare.

135 Background: High-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplant (HSCT) has been used as part of the treatment of metastatic breast cancer. However, the evidence behind this approach continues to be controversial. We hypothesize that previous radiation therapy (RT) may increase the risk of cardiomyopathy and mortality in these patients. Methods: Patients who underwent HSCT after HDCT for breast cancer treatment during 1988-2012 were included. The patients that underwent HSCT for indications other than breast cancer were matched 1:2 based on age and gender. The data was analyzed using the cox proportional hazard model, looking at time-to-survival with adjustments made for cardiotoxic chemotherapeutics, histology of cancer, ER/PR status, EGFR mutation status, number of RT sessions, age, and functional status. Results: Sixty-six patients with metastatic breast cancer underwent HSCT. Patients with breast cancer were more likely to develop systolic heart failure (10% vs. 6.1%, p=0.002). There were 29 (43.9%) patients who underwent whole breast RT (WBRT). Prior WBRT was an independent predictor of developing post-transplant systolic heart failure (HR 3.77; 95% CI 1.29–10.75, p=0.007). The Kaplan–Meier curve shows a better survival for patients without a previous WBRT (Log rank p=0.009). Patients with prior WBRT were found to have decreased survival (HR 1.59; 95% CI 1.16–2.17, p=0.004). Conclusions: Patients with a history of WBRT who underwent HSCT were more likely to develop new onset systolic heart failure than patients without WBRT. This might be due to the effects of RT on the coronary arteries and the cardiac myocytes, leading to worse outcomes. Future studies are needed to evaluate outcomes of HSCT in patients with metastatic breast cancer without prior WBRT.