ALBERT

Description: Introduction: Immune Thrombocytopenia (ITP) is a disease of immune-mediated destruction of platelets and suppression of platelet production. ITP has been historically treated with corticosteroids and/or immune globulins as first-line agents. There are several second-line treatments available, should patients fail to respond to initial therapy or relapse after it is tapered. These include eltrombopag, romiplostim, rituximab and splenectomy. This study utilized a national electronic health record (EHR) database to begin to explore the real world treatment patterns of the aforementioned second-line (index) therapies. Methods: Utilizing the Optum EHR database, we identified patients who initiated their first second-line treatment (i.e. the index treatment) with eltrombopag, romiplostim, rituximab or splenectomy from Jan. 1, 2009 to Sep. 30, 2016 for primary or unspecified ITP. Patients included in the analysis had the following characteristics: 18 years or older; previous treatment with corticosteroids and/or immune globulin products; active in the database for at least 6 months prior to and 12 months post initiation of the index treatment. Outcomes that were evaluated after initiation of the index treatment included: (1) Duration of therapy for eltrombopag and romiplostim; (2) Proportion of patients who started a subsequent line of treatment after their index treatment; (3) Treatment free duration between the end of the index treatment and start of a subsequent line of treatment; and (4) Proportion of patients using a first-line medication (corticosteroids and/or immune globulin) during treatment with eltrombopag and romiplostim. Chi-square and t-tests were used for statistical analysis. Results: 2,047 patients met the inclusion criteria and used an index treatment as follows: eltrombopag, N=110 (5.4%); romiplostim, N=189 (9.2%); rituximab, N=1488 (72.7%); splenectomy, N=260 (12.7%). The mean age was 60.8 years (standard deviation [SD]: 17.4), with 52.4% female and mean Charlson comorbidity score of 2.1 (SD: 2.1). Treatment duration was 481 days for eltrombopag versus 346 days for romiplostim (p=0.033). The proportion of patients who started a subsequent line of treatment after their index treatment ranged from 41% for rituximab to 49% for splenectomy (p=0.071). Treatment free duration between the end of the index treatment and start of a subsequent treatment ranged from a mean of 248 days for romiplostim to 575 days for splenectomy (p

Description: Immunodeficiency-associated lymphoproliferative disorders (IA-LPDs) are pathologically and clinically heterogeneous. In many instances, similar features are shared by a spectrum of IA-LPDs in clinically diverse settings. However, the World Health Organization (WHO) classifies IA-LPDs by their immunodeficiency setting largely according to the paradigm of posttransplant lymphoproliferative disorders but with inconsistent terminology and disease definitions. The field currently lacks standardization and would greatly benefit from thinking across immunodeficiency categories by adopting a common working vocabulary to better understand these disorders and guide clinical management. We propose a 3-part unifying nomenclature that includes the name of the lesion, associated virus, and the specific immunodeficiency setting for all IA-LPDs. B-cell lymphoproliferative disorders (LPDs) are usually Epstein-Barr virus (EBV)+ and show a spectrum of lesions, including hyperplasias, polymorphic LPDs, aggressive lymphomas, and, rarely, indolent lymphomas. Human herpes virus 8–associated LPDs also include polyclonal and monoclonal proliferations. EBV− B-cell LPDs and T- and NK-cell LPDs are rare and less well characterized. Recognition of any immunodeficiency is important because it impacts the choice of treatment options. There is an urgent need for reappraisal of IA-LPDs because a common framework will facilitate meaningful biological insights and pave the way for future work in the field.

Description: Introduction: Chronic immune thrombocytopenia (cITP) is an autoimmune disorder defined by low platelet count (

Description: Key Points DUSP22-rearranged ALCLs belong to a distinct subset of ALCLs lacking activated STAT3. DUSP22-rearranged ALCLs have a unique molecular signature characterized by DNA hypomethylation and an immunogenic phenotype.

Description: Background and Purpose: Penile erection and detumescence are complex physiologic processes, which require delicate neurohormonal and cardiovascular response. Priapism is defined as a persistent and painful erection lasting longer than four hours without sexual stimulation. Stuttering priapism is characterized by a self-limited, recurrent, and intermittent erection, frequently occurring in patients with sickle cell disease(SCD). The aim of this study was to identify the clinical and laboratory features in SCD patients with priapism in Oman. Methodology: In this retrospective case-control study, medical records of all patients with SCD who developed priapism were retrieved from the hospital information system and compared in a 1: 1 ratio with age and gender matched SCD patients who did not ever had priapism. Addition information extracted include hematological and laboratory parameters, treatment, and complications. Data obtained were analyzed using IBM SPSS version 23. The study was conducted following approval from the hospital medical research and ethics committee. Results & Discussion: Amongst the forty-one SCD patients evaluated, in the 21 patients with priapism (mean age 24.7 yrs), there was a significantly higher WBC, platelet, retic counts, LDH and serum total bilirubin as compared to controls (p

Description: Background: Sickle Cell Disease represents a national health problem in Saudi Arabia with close to 150 thousands of the population are afflicted with the disease. Patients are frequently admitted with life threatening complications like Acute chest syndrome (ACS), Hyperhemolysis (HH), pneumonia, thromboembolism including pulmonary Artery Thrombosis (PAT) or severe protracted painful vasoocclusive crises (VOC). Rapid lowering of Hemoglobin S helps in reducing sickling and in alleviating such complications and allowing rapid recovery. Exchange transfusion is the fastest way to remove pathogenetic sickling red blood cells and reducing Hb S level to a safe level. It can be done manually (Mex) or via Automated Erythrocytopharesis machine (AECP). In this study we compared manual exchange to AECP in achieving the targeted lowering of Hb S and in accelerating clinical recovery. Patients and Methods: Patients included are sickle cell disease patients (HbSS, HbSC, Hb S/thal) admitted to the ER of a central Hospital. Indications of exchange were: acute chest syndrome, acute severe painful vaso-occlusive crises refractory to standard ER protocol of analgesia, stroke, priapism, Hyperhemolysis, and acute pulmonary embolism. P value of significance was calculated using student t-test comparing between median Hb S achieved after manual exchange vs AECP. To assess the rapidity of reversal of desaturation in acute chest syndrome patients, the cumulative incidence of reversal of desaturation and normalization of Oxygen saturation on room air were plotted against time at 0 time of the start of exchange, 2 hours,4 , 12, 24, 48 and 72 hours/discharge (D/C) Results: Table 1 shows clinic-biological characteristics of patients who underwent exchange transfusion. A total of 230 patients-admissions were registered between Dec 1. 2017 to July 27, 2018 for painful VOC to ER; 51 (32%) had clinical indications for exchange (ACS 25, Stroke / fits 1, priapism 1, pulmonary artery thrombosis 1, Hyperhemolysis with VOC (n:7) , VOC with HLH (n:1), and the remaining with "refractory" painful VOC with or without infection. One patient died immediately at the time of arrival to ER before starting any standard resuscitative measures . Exchange transfusion was indicated and done for 53 (23%); 12 (22,6%) AECP and the remaining (77.4%) had Manual Exchange. The median Hb S after manual exchange was 44 % (range 31-74%) which was unsatisfactory and way higher than the targeted level while Automated ECP reached down satisfactorily to a median of 31%(range 8%-50%) ; 67% of whom achieved it with only one session. No mortalities or major procedure related complication reported with manual or automated ECP. Procedurally, 3 patients needed 2 automated sessions and 1 patient used 2 kits for one session. Manual exchange could not achieve the target Hemoglobin S level below or around 30% due to logistic and technical difficulties and sometimes patients' refusal while Automated ECP reached to a mean Hb s level of 28%( range 8%-50%) and nearly two thirds (67%) reached to as low as 31% Hb S level with only one session of Automated ECP and was associated with rapid improvement of the oxygenation within the first 2 hours of the procedure. Conclusions: Erythrocytopharesis (Automated RBC exchange) is effective, quick and safe procedure that is life saving for many patients with ACS and is associated with less difficulties and complications if compared with the manual exchange. Because SCA is a national problem in Saudi Arabia and acute chest syndrome and other acute major complications comprehensively kill SCD patients, Automated Erythocytopharesis should be available nation-wide like dialysis machines at all large hospitals in all cities and should be distributed according to the prevalence of SCA in the area or location. Disclosures No relevant conflicts of interest to declare.

Description: Background: Severe Aplastic Anemia (SAA) is a rare bone marrow disorder characterized by inadequate levels of peripheral, multi-lineage blood cells. Of the two available first-line treatments for SAA, allogeneic hematopoietic stem cell transplantation is limited by patient eligibility and donor availability, and immunosuppressive therapy (IST) is characterized by a significant proportion of non-responders, toxicity, and risk of transformation to diseases such as acute myelogenous leukemia. Patients who do not respond to treatments become transfusion dependent, which has a significant impact on patients' quality of life as well as healthcare costs. Eltrombopag is the only TPO-R agonist approved for the treatment of refractory SAA. In a Phase I/II clinical trial, eltrombopag, given in association with IST, showed efficacy in patients with naive-SAA, and offers a significantly improved first-line alternative to patients affected by SAA (Townsley, et al 2017). In the US healthcare environment, there is a need to compare costs and consequences to understand value. Objective: Evaluate eltrombopag as a first-line treatment versus IST alone for SAA from the American private healthcare system perspective. Methods: A responder model for newly diagnosed SAA patients was created to assess the treatment pathway and economic impact of including eltrombopag in addition to IST (antithymocyte globulin and cyclosporine A) as a first-line treatment. A simulated cohort with two treatment arms underwent 6 months of treatment with either eltrombopag in addition to IST or with IST alone and were followed for a 3-year time period. Each arm received a diagnostic test measuring response at 6 months. Patients who achieved complete or partial response in either arm received low-dose cyclosporine A as maintenance therapy for an additional 6 months of treatment. Patients who did not respond in either arm continued with eltrombopag monotherapy as a second-line therapy for an additional 6 months. First-line therapy (eltrombopag with IST, IST alone), maintenance therapy (low-dose cyclosporine A), second-line therapy (eltrombopag monotherapy), administration, routine care, mortality and adverse event costs were included in the analysis. Workplace productivity related costs were not considered. Response rates, mortality, dosing, treatment duration and adverse event rates for each arm were based on a phase I/II trial (Townsley, et al 2017). Drug costs were obtained from a large online database (REDBOOK Online). Administration costs were based on the 2017 CMS Medical Fee Schedule. Routine care rates (visits, hospitalizations, tests and transfusions) were based on published data (Peffault De Latour, et al, 2017). Routine care, mortality and adverse event costs were based on CPT codes from the American Medical Association, HCUPnet and published data (Toner, et al 2011). All cost data are reported in 2018 US dollars. See figure 1 for details. Results: In a simulated cohort with a population of one million, the annual incidence of aplastic anemia was 0.000234% and SAA accounted for 83.8% of those cases. The two treatment paths were compared for their consequences. Based on the clinical trial data, in the treatment arm with eltrombopag and IST, 94% of patients experienced treatment response relative to the IST arm where only 66% of patients experienced treatment response. Further, in the treatment arm with eltrombopag and IST, the patients experienced a reduced annual risk of mortality by 0.3% relative to the IST arm. Use of eltrombopag therapy as a first-line therapy produced a cost increase of $77,442 over 3 years. First-line drug costs accounted for an increase of $109,147, while improvements in response rates led to cost offsets for second-line drugs and produced $29,663 in savings. Adverse event, routine care and mortality costs had relatively negligible effects on either treatment arm over a 3-year time period. Sensitivity analyses confirmed the robustness of the analysis. Conclusion: When following treatment approaches specified in clinical studies, high response rates combined with reduced risk of mortality and less usage of rescue medication, and a low disease incidence are likely to lead to manageable economic consequences with eltrombopag + IST therapy from the American private healthcare system perspective. In a simulated cohort with a population of one million, this was estimated to be $77,442 over 3 years. Disclosures Said: Novartis: Employment. Cai:Novartis: Employment. Forsythe:Novartis: Consultancy. Roy:Novartis: Employment.

Description: INTRODUCTION: Immune Thrombocytopenia (ITP) is a disease of immune-mediated destruction of platelets and suppression of platelet production. ITP has been historically treated with corticosteroids and/or immune globulins as first-line agents. There are several second-line treatments available, should patients fail to respond to initial treatment or relapse after it is tapered. This study utilizes a national electronic health record (EHR) database to understand clinical outcomes with use of second-line treatments including: thrombopoietin receptor agonists (specifically, eltrombopag and romiplostim), rituximab, and splenectomy. METHODS: Utilizing the Optum EHR database, we identified patients who initiated a second-line treatment from Jan. 1, 2009 to Sep. 30, 2016 for primary or unspecified ITP. Additionally, patients included in the analysis had the following characteristics: 18 years or older; previous treatment with corticosteroids or immune globulin products; and active in the database for at least 6 months prior to and 12 months post initiation of a second-line treatment. Evaluated outcomes included: (1) platelet counts; (2) bleeding related episodes (BREs); and (3) thrombotic events (TEs), including stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, and pulmonary embolism. All outcomes were evaluated over the 12-month period following the initiation of second-line treatment. BREs and TEs were defined using ICD codes, collapsed to first three characters, indicating a form of bleeding or thrombotic events. Chi-square test and t-test were used to evaluate differences among the four treatment cohorts (eltrombopag, romiplostim, rituximab, and splenectomy). RESULTS: 2,047 patients met the inclusion criteria and used the second-line treatments as follows: eltrombopag, N=110 (5.4%); romiplostim, N=189 (9.2%); rituximab, N=1,488 (72.7%); splenectomy, N=260 (12.7%). The mean age was 60.8 years (standard deviation [SD]: 17.4), with 52.4% female and mean Charlson comorbidity score of 2.1 (SD: 2.1). Compared with platelet counts at the initiation of second-line treatments (collected within +/- 14 days of initiation of second-line treatments), mean platelet counts achieved during the 12 months post initiation of a second-line treatment increased in all treatment cohorts, ranging from an increase of 63,000/μL for rituximab to an increase of 157,000/μL for splenectomy. Mean platelet counts achieved during the 12 months post initiation of a second-line treatment differed significantly across treatment cohorts, ranging from 102,000/μL for eltrombopag to 240,000/μL for splenectomy (p