ALBERT

Description: Introduction: Electronic consultation (e-consult) is a healthcare delivery method in which a consultant provides input on the management of a patient by reviewing the medical chart without a face to face visit. This method is especially suited to systems that use a comprehensive electronic medical record (EMR). E-consults have the potential to improve efficiency and timeliness of care, save costs, prevent unnecessary patient visits, and address shortage of specialists. They may be especially valuable in rural areas, and for patients who have difficulty traveling. Published data regarding the utility and efficacy of remote hematology consultations are limited. At the VA Connecticut Healthcare System (VACT) electronic hematology consultations were initiated in July of 2011 as part of a national program. Providers are allowed to choose between referring their patient to a face to face visit or an e-consult, based on their clinical judgment and their patients’ preferences. The purpose of this study is to evaluate the impact of electronic hematology consultation on patient care, to measure its effect on the face-to-face encounters at the VACT hematology clinics, and to assess provider and patient satisfaction. Methods: We conducted a retrospective review of 300 patients who had a hematology e-consult between the years 2011 to 2013 at VACT. Data abstracted included demographics, diagnoses, timeliness of care, and need for face to face visits. In addition patient and provider satisfaction were evaluated by anonymous surveys. Hematology e-consults were performed by board eligible/certified hematologists based on review of the EMR and peripheral blood smears as appropriate. When necessary, recommendations were made to refer a patient for a face to face evaluation in the hematology clinic. Our study was approved by our local IRB. Results: The most common reason for a hematology e-consult was anemia (25%), followed by anticoagulation in patients with venous thromboembolism (14%), thrombocytopenia (8%), erythrocytosis (7%), leukocytosis (6%), paraproteinemia (6%), neutropenia (6%), pancytopenia (2%), abnormal iron indices (2.5%) and abnormal coagulation profiles (2%). Additional reasons included thrombocytosis, macrocytosis, lymphocytosis, eosinophilia, thalassemia, splenomegaly, lymphadenopathy, and hemoglobinopathies. The vast majority of patients were male (95%) with an average age of 63 +16 years. Average distance between the patients’ homes to our medical center was 36.6+22 miles. Electronic hematology consultations were completed on average within 16 days. We observed that implementation of hematology e-consults was accompanied by a 15% decrease in the annual number of face to face hematology visits (from 377 in 2011 to 319 in 2013), while the number of Veterans enrolled at VACT during that period did not change significantly. Only in 42 patients (14%) a face to face hematology consultation was recommended after completion of the e-consult. Of the 50 patients that were sent satisfaction surveys, completion rate was 34% and 65% replied that they preferred an e-consult over a face to face visit. Among 61 providers that received surveys, 15 (25%) responded and 100% indicated that they were “satisfied” or “very satisfied” with the process. Conclusions: Our study suggests that electronic hematology consultation can address many common hematology diagnoses and can prevent the need for a face to face visit in the majority of patients selected for an e-consult by their referring providers. These consultations can be provided without compromising patient and provider satisfaction and may decrease the need for face to face visits. This could have important implications for the delivery of hematology care, especially in healthcare systems that utilize an EMR. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Benign Ethnic Neutropenia (BEN) is the most common form of neutropenia worldwide and is usually defined as a neutrophil count under 1.5x103/uL without increased infection risk. BEN has been observed predominantly in individuals of African ancestry as well as in certain Middle Eastern ethnic groups. The discovery of neutropenia during routine laboratory testing, however, may prompt extensive workup for infectious, autoimmune, and hematologic disorders. Identifying a readily available test to diagnose BEN in the appropriate ethnic and clinical setting could preempt unnecessary and invasive testing such as a bone marrow aspiration and biopsy and minimize patient anxiety. The absence of the red blood cell (RBC) Duffy antigen, Fy (a- b-), is thought to be responsible for BEN. As the Duffy antigen is utilized by the parasite Plasmodium vivax to enter the RBC, it has been hypothesized that in West Africa, positive selection for the null allele enabled individuals to be protected against infection and have a survival advantage. Aim: Our study examined whether testing for the Fy phenotype could reliably be used as a clinical assay to identify patients with BEN. Methods: Our cases included patients at the VA CT Healthcare System clinically diagnosed with BEN and controls that were chosen randomly from the pools of patients for whom a CBC and type and screen were checked for any other reason. Both probable BEN cases and controls were tested for the Fy phenotype using standard serologic methods in the blood bank. The Fy phenotype, absolute neutrophil count (ANC), white blood cell count (WBC), hemoglobin level, platelet count, and medical diagnoses were extracted from the medical record. Applicable data were compared statistically using the Mann-Whitney U Test with significance set at p 〈 0.05. Results: Our study included 32 patients (mean age 54, range 21 to 90) who were clinically identified as probable BEN cases and 50 patients (mean age 68, range 38 to 97) chosen as controls. In the probable BEN group, 28 patients self-identified as African American or Black and 3 declined self-identification. In the control group, 11 patients self-identified as African American or Black, 34 self-identified as White, 2 self-identified as Hispanic, 2 declined self-identification, and 1 self-identified as Native Hawaiian. The majority of probable BEN patients (31 of 32) and only a minority of control patients (6 of 50) were Fy (a- b-). Most study patients were male: 30 of 32 probable BEN patients and all control patients were male. The mean ANC count for Fy(a- b-) probable BEN patients was significantly lower than controls (1.68x103/uL versus 5.46x103/uL, p 〈 0.0001). Similarly, the mean WBC count for Fy (a- b-) probable BEN patients was significantly lower than the mean WBC for controls (3.72 x 103/uL versus 8.14 x 103/uL, p 〈 0.0001). Hemoglobin was comparable between Fy(a- b-) probable BEN patients and controls (12.91 g/dL versus 11.68 g/dL, p = 0.0673) as were platelets between Fy(a- b-) probable BEN patients and controls (194x103/uL versus 213x103/uL, p = 0.4354). The only African American patient presumed to have BEN that was not confirmed by Fy testing was found to have concurrent diagnoses that could otherwise explain his neutropenia (HIV/HCV). The remaining confirmed BEN cases did not have an accompanying marrow suppressive hematologic disorder. Five control group patients had potentially marrow suppressive hematologic disorders including myelodysplastic syndrome and acute myeloid leukemia. Conclusions: Readily available serologic testing in the blood bank for Duffy antigen phenotyping can be used to confirm suspected BEN in patients with high clinical suspicion. Further testing is in progress of Fy phenotyping comparing controls with neutropenia for any reason to our proposed BEN population to better determine the positive predictive value. Fy phenotyping to confirm BEN suspicion may help avoid unnecessary and invasive neutropenia testing. In addition, since BEN affects certain ethnic groups (primarily those of African ancestry), these individuals may be unfairly excluded from possible treatment including cytopenia-inducing psychiatric medications like clozapine, myelosuppressive chemotherapy, and clinical trials due to ANC eligibility requirements. Fy phenotyping to confirm clinical suspicion of BEN could be a useful tool to help develop modified guidelines for neutropenia-inducing medication. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: HIV infection and the resulting immunodeficiency predispose individuals to various plasma cell disorders including reactive plasmacytosis, monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plamacytomas. Studies have demonstrated nearly 4.5-fold increased risk of MM in HIV-infected (HIV+) individuals. Limited evidence from case reports/small series of MM in HIV+ patients have suggested a younger age at presentation, more disseminated disease, an aggressive clinical course and inferior outcomes as compared to uninfected counterparts. However, these studies included small numbers of patients, and often lacked appropriate comparison groups. We aim to compare clinical characteristics and outcomes of HIV+ and uninfected subjects with MM, with the hypothesis that significant differences will be detected between the two groups. Methods: We analyzed all patients with histologically proven MM in the Veterans Aging Cohort Study (VACS). VACS is a prospective, observational cohort, beginning in 1996, of 〉 40,000 HIV+ and 〉 80,000 age-, race/ethnicity-, sex-, and clinical site- matched (1:2) uninfected patients under care in the Veterans Health Administration. Clinical variable were obtained via chart review. The variables studied included stage at diagnosis (Durie-Salmon and International Staging System- ISS), bone marrow plasma cell involvement at diagnosis, presence of asymptomatic vs clinical MM, involvement with bone lesions at diagnosis, and presence of extramedullary (EM) involvement during the course of disease. Differences between the HIV+ and uninfected patients were compared using appropriate bivariate methods (chi-squared or Fisher's test, where applicable). All p values were two sided and the level of significance chosen was 0.05. Results: A total of 162 patients (62 HIV+, 100 uninfected) with MM were included in this study. Patients were predominantly male 99.4%; 57% were black, 28% white, 15% Hispanic or other ethnicity. Average age at the time of diagnosis was 59, and did not differ between the two groups. The distribution by Durie-Salmon stage was as follows: 28% stage 1, 18% stage 2 and 54% stage 3. By ISS, 43% had stage 1, 25% had stage 2 and 31% had stage 3 disease. 10% had asymptomatic disease. 54% had lytic lesions on skeletal survey. When HIV+ and uninfected patients were compared, based on the available data, there were no statistically significant differences in the distribution of MM by stage, presence of clinically symptomatic MM or presence of lytic lesions. However, we observed a significantly higher rate of the presence of extramedullary disease in the HIV+ as compared with uninfected group (〉1 EM site 21% vs 19%, 1 EM site 21% vs 11%, none 57% vs 78%; p value 0.02). Comparison of overall survival between the two groups, and analysis of the impact of HAART on survival are ongoing. Conclusion: This is the largest published study to date to compare the clinical characteristics and outcomes of MM between HIV+ and uninfected individuals. We observed a significantly higher rate of EM disease in the HIV+ group, an important finding since EM disease is associated with poor prognosis. Ongoing analysis will provide additional data on treatment responses, including the role of HAART, and a comparison of clinical outcome data between these two groups. Disclosures No relevant conflicts of interest to declare.

Description: Background Protein disulfide isomerase (PDI) is a thiol isomerase secreted by platelets and endothelial cells and is required for thrombus formation. We previously showed that quercetin flavonoids inhibit PDI and block thrombus formation following vascular injury in a mouse model. Quercetins are present in a wide range of fruits and vegetables and epidemiologic data suggest an antithrombotic effect. Initial human studies demonstrated that the oral administration of isoquercetin reduces PDI activity in plasma. To evaluate the antithrombotic strategy of inhibiting PDI, we performed a phase II trial to evaluate the efficacy of isoquercetin to reduce the hypercoagulability of cancer patients at high risk for venous thromboembolism (VTE). In high-risk cancer cohorts with protocol-mandated screening for VTE, the reported incidence of VTE often exceeds 20% within months of initiation of chemotherapy. The risk of major hemorrhage is also higher in patients with advanced cancer which complicates the decision to recommend thromboprophylaxis. Methods We performed a phase II study at 11 sites to assess the safety and efficacy of isoquercetin in cancer patients at high risk for VTE. Cohort A received isoquercetin 500 mg daily and Cohort B received 1000 mg isoquercetin daily for 56 days with laboratory assays performed at the beginning and at completion of study. Eligible patients had locally advanced or metastatic pancreatic, non-small cell lung, or colorectal cancer and enrolled within 4 weeks of initiating first or second line chemotherapy. The primary endpoint of the study was a reduction in D-dimer at day 56. Patients were monitored for the development of venous thromboembolism including a protocol-required bilateral lower extremity ultrasound performed at day 56. The primary VTE endpoint was defined as any symptomatic proximal or distal lower extremity DVT, symptomatic pulmonary embolism or fatal PE, or asymptomatic proximal DVT diagnosed by screening compression ultrasound. Radiology images for all suspected VTE were centrally reviewed and adjudicated by an independent committee. Results There were no primary VTE endpoints observed in either cohort. Paired plasma samples were analyzed in 25 patients who received isoquercetin 500 mg daily (Cohort A) and 21 patients who received the isoquercetin 1000 mg daily (Cohort B). For the primary D-dimer endpoint, the administration of isoquercetin 1000 mg decreased D-dimer plasma concentrations by a median of 20% equating to a median decrease of 206 ng/ml fibrinogen equivalent units (P

Description: Tumor microenvironment (TME) is commonly implicated in regulating the growth of tumors, but whether it can directly alter the genetics of tumors is not known. Genomic instability and dendritic cell (DC) infiltration are common features of several cancers, including multiple myeloma (MM). Mechanisms underlying genomic instability in MM are largely unknown. Here, we show that interaction between myeloma and DCs, but not monocytes, leads to rapid induction of the genomic mutator activation-induced cytidine deaminase (AID) and AID-dependent DNA double-strand breaks (DSBs) in myeloma cell lines as well as primary MM cells. Both myeloid as well as plasmacytoid DCs have the capacity to induce AID in tumor cells. The induction of AID and DSBs in tumor cells by DCs requires DC-tumor contact and is inhibited by blockade of receptor activator of NF-κB/receptor activator of NF-κB ligand (RANKL) interactions. AID-mediated genomic damage led to altered tumorigenicity and indolent behavior of tumor cells in vivo. These data show a novel pathway for the capacity of DCs in the TME to regulate genomic integrity. DC-mediated induction of AID and resultant genomic damage may therefore serve as a double-edged sword and be targeted by approaches such as RANKL inhibition already in the clinic.