ALBERT

Description: Introduction: Thrombocytopenia is a common reason for referral to a hematology clinic. Determining the underlying etiology can be challenging as common diagnoses including immune thrombocytopenia (ITP), myelodysplastic syndrome (MDS) and familial thrombocytopenia lack specific or easily identifiable diagnostic markers. Thus, the reliability of the diagnosis is uncertain, which has implications for patient management and eligibility for clinical trials. The objective of this study was to determine the reliability of the diagnosis of thrombocytopenia in the outpatient setting among 3 independent adjudicators. Methods: We selected 20 patients referred to a tertiary hematology clinic with thrombocytopenia, who were enrolled in a prospective observational registry study (the McMaster ITP Registry). The most common diagnoses that appeared in the registry were represented: Primary ITP (n=9); secondary ITP (n=3); familial thrombocytopenia (n=3); hypersplenism (n=3); and MDS (n=2). Blinded to the diagnosis, 3 hematologists with clinical and research experience in thrombocytopenic disorders independently reviewed all source documentation, which included referral notes, consultation and follow up notes, results of pertinent investigations, treatments administered and response to treatments. Adjudicators chose one diagnosis from a list (primary ITP, secondary ITP, MDS, thrombocytopenia of pregnancy, thrombocytopenia of malignancy, familial thrombocytopenia, splenomegaly, liver disease, thrombotic microangiopathy, cyclic thrombocytopenia, Evan’s syndrome or unknown) and were invited to explain how they did or did not arrive at the diagnosis. Agreement among the 3 adjudicators and between each adjudicator and the initial diagnosis was calculated using Fleiss’s kappa (k). Results: Overall agreement among the reviewers for the diagnosis of thrombocytopenia was moderate (k=0.51, 95% confidence interval, 0.39 to 0.63). All 3 adjudicators had perfect agreement for 10 of 20 patients with primary ITP (n=5), secondary ITP (n=3), and MDS (n=2). Median nadir platelet count for the group with ITP (primary or secondary) was 4 x109/L (IQR 3x109/L to 5x109/L). These patients demonstrated a platelet count response after corticosteroids or intravenous immune globulin (IVIg) or after treatment of their underlying disease (e.g. response to HAART in HIV-associated ITP). For 6 patients, 2 out of 3 adjudicators agreed on the diagnosis of primary ITP (n=2), familial thrombocytopenia (n=1), hypersplenism (n=1) and liver disease (n=2). 4 of these diagnoses (2 ITP, 1 familial, 1 hypersplenism) matched the initial diagnosis in the chart. For 4 patients, all 3 adjudicators arrived at different diagnoses of either familial thrombocytopenia, primary ITP, or unknown. The median nadir platelet count among those patients was 38 x109/L (IQR 29x109/L to 45x109/L). Two of these patients never received treatment for thrombocytopenia; one patient had no response to corticosteroids or IVIg. Adjudicators reported that the diagnosis of ITP hinged on the patients’ response to IVIg and “unknown” cause was selected when insufficient platelet count measurements were available or other potentially relevant investigations (e.g., bone marrow aspirate) were missing. Conclusion: Inter-rater reliability for the diagnosis of thrombocytopenic disorders was moderate. Agreement was highest for patients with ITP (primary and secondary) who had severe thrombocytopenia (platelet count

Description: Introduction: Immune thrombocytopenia (ITP) is a common platelet disorder; however, it is a heterogeneous disease and optimal treatment has not been established. Understanding the epidemiology of ITP requires large observational cohort studies and prospective registries with prolonged follow-up. We established the McMaster ITP Registry to study the natural history of ITP and to identify clinical and laboratory features that may distinguish disease subgroups. The objectives of this study were 1) to assess the accuracy of data collection in the McMaster ITP Registry; and 2) to describe the prevalence, clinical features and platelet autoantibody results from a large cohort of ITP patients. Methods: The McMaster ITP Registry enrolls consecutive adult patients with thrombocytopenia (platelet count 0.8 for each); yet, to improve the method of capturing diagnosis and disease stage, we removed a category (‘mild thrombocytopenia’), renamed a category (‘liver disease’) and added a category (‘unknown cause’) following this validation exercise. Conclusion: In the setting of a tertiary hematology referral clinic, 55% of patients presenting with thrombocytopenia had ITP. Of patients with primary ITP, 55.3% had anti-platelet autoantibodies. Our classification of patients by diagnosis of thrombocytopenia was simplified after the validation study. The McMaster ITP Registry can help identify clinical and laboratory features of ITP patients to better understand natural history and treatment responses. Disclosures Arnold: GSK: Honoraria, Research Funding; Hoffman-LaRoche: Research Funding; Bristol Myers Squibb: Consultancy; Amgen: Consultancy, Honoraria, Research Funding.

Description: Introduction Thrombotic thrombocytopenic purpura (TTP) is a prothrombotic disorder characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia. It has been associated with a deficiency or dysfunction of ADAMTS13, an enzyme responsible for cleaving ultra-large von Willebrand factor multimers, thus preventing spontaneous platelet adhesion and aggregation. In its absence, platelet aggregates accumulate in the microvasculature causing neurological symptoms, cardiac ischemia and renal dysfunction. Most cases in adults are idiopathic, and associated with severe ADAMTS13 deficiency (

Description: Introduction: Adult T-cell leukemia/lymphoma (ATLL) is a rare, aggressive peripheral T-cell lymphoma, affecting patients from HTLV-1 endemic areas including Japan, the Caribbean, Latin America, Africa, and Northern Iran. Most of the literature regarding prognosis and management reflects experience from Japan, where the demographic and clinicopathologicfeatures may differ from other endemic countries. There are limited data on clinical presentation and treatment outcomes of patients from North America (NA) with ATLL (Philips, Cancer, 2010). Based on the available literature, however, prognosis remains poor, with few effective chemotherapeutic options. We performed a retrospective analysis of patients with ATLL presenting to a NA tertiary care center. Our primary objectives were to (a) describe patient demographics, ATLL subtype, and presentation characteristics, (b) identify progression free survival (PFS) and overall survival (OS), (c) identify the impact of consolidation antiviral therapy on duration of response in this high-risk patient population. Methods: Patients with ATLL were identified from prospectively populated lymphoma and leukemia databases at Princess Margaret Cancer Centre (PMCC) referred for primary therapy; patients referred at relapse or for consideration of treatment in first response were also included if they received therapy at PMCC. Patients were included if they met current criteria for ATLL and had a positive HTLV-1 antibody test. Additional data were collected from patient charts including ethnicity, ATLL subtype, initial treatment, and response to therapy. Descriptive statistics were used to evaluate demographic data, ATLL subtype,immunophenotype, first-line therapy, and response. In patients who achieved a partial or complete response following first line therapy, a t-test was used to identify the impact of consolidative antiviral therapy on duration of response. Twenty-eight patients received their first-line therapy at PMCC and Kaplan-Meyer estimates were used to calculate the PFS and OS for this population. Results: Forty-three patients with ATLL were referred to PMCC from 1993 to 2014. Median age at diagnosis was 46 years (20-69) and 55.8% were females (Table 1). The majority were of Caribbean descent (63%), followed by African (5%), Asian (3%), Middle Eastern (3%), or undocumented country of origin (28%). ATLL subtype consisted of lymphomatous (44%), acute (35%) and smoldering (2%); subtype could not be fully determined in 28% of cases. 88% of patients were treated with front-line chemotherapy and 12% treated with upfront antiviral therapy alone (interferon alpha with or without antiretroviral therapy). At presentation, 16 (37%) patients had bone marrow involvement, 11 (26%) had CNS involvement, 5 (12%) had lytic lesions, 5 (12%) had skin involvement, and 7 (16%) had hypercalcemia. Immunophenotype based on flow cytometry of peripheral blood or lymph node biopsy was available for 27 patients. Twelve patients (44%) were positive for CD4, CD5, CD3, CD2 and CD25; 3 were double positive for CD4 and 8. The majority of patients were CD7 negative (78%) and commonly CD8 negative (44%). Three patients were also negative for CD25 (11%). Following primary chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone, 30% (13 of 43) patients achieved a partial or complete remission; the remaining 30 patients experienced disease progression during or at completion of chemotherapy. All responding patients experienced disease relapse; median duration of response was 17.4 months. Five patients (38.5%) received consolidative antiviral therapy, however, there was no statistically significant difference in duration of response (p=0.20). Twenty eightpatients received first-line therapy at PMCC. Median PFS for this group was 0.42 years (95% confidence interval 0.16 to 1.25) (Figure 1). Median OS 1.29 years (95% confidence interval 0.57 to 2.26) (Figure 2). Conclusion: The outcome of patients with ATLL in this retrospective observational study are very poor. Within the limits of the nationalities of patients referred to ourcenter, NA ATLL patients present with acute or lymphomatous subtypes, and have a high incidence of CNS involvement. Complete response rate to chemotherapy commonly used in other T cell lymphomas is low, and incorporation of alternative regimens and antibody therapies should be tested in primary therapy of ATLL. Disclosures Kuruvilla: Celgene: Consultancy, Honoraria; Amgen: Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Roche Canada: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Merck: Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Honoraria. Kukreti:Lundbeck: Honoraria; Amgen: Honoraria; Celgene: Honoraria.

Description: Background Multiple myeloma (MM) is an incurable hematological malignancy of older adults. Autologous stem cell transplant (ASCT) remains a standard of care with multiple retrospective and registry cohort studies demonstrating its efficacy in MM patients including older adults with the disease. Despite this favourable data, there remains wide heterogeneity in the utilization of ASCT, particularly among older adults with MM. We conducted a mixed methods study from the perspective of both oncologists and older adults with MM to: 1) identify decision making factors that influence ASCT eligibility and 2) to explore any barriers to ASCT utilization. Methods We conducted a mixed methods study at two academic centres and two community centres in Ontario, Canada. Older adults with MM (aged 65-75) who were within one year of treatment decision making regarding ASCT were invited to complete a survey from outpatient clinics. Oncologists (both community & academic) were recruited via email. Semi-structured interviews were conducted with all participants who agreed to an interview. Thematic analysis was conducted to identify themes from the transcripts using NVivo (qualitative analytical software). The initial 3 transcripts were independently coded by two investigators, to develop a codebook. Any discrepancies were resolved using consensual validation. Once consensus was reached, the codes were then applied to the rest of the transcripts by one coder. A convergent parallel approach was used in combining the results of the qualitative and quantitative sections of the study. Results A total of 15 oncologists and 18 patients with MM completed the surveys. Baseline patient and oncologist characteristics are listed in Table 1. The majority of patients were offered an ASCT (78%) and among those offered, 79% went ahead with ASCT. Most patients were happy with the decision to either go ahead or refuse the transplant as indicated by a low decisional regret score (median of 5 and IQR of 0-19 out of 100, with a lower score indicating less regret with the decision). With regards to oncologists, 80% stated they were aware of geriatric tools to help with treatment risk stratification; however, the majority (75%) used none of these tools and relied on the 'eye-ball' test for decision making. Nine oncologists and 9 patients completed the semi-structured interview. Summarized themes identified are shown in Figure 1. From the perspective of patients, factors that most affected ASCT decision making were: strong trusting relationship with their oncologist (n=9), family support (n=9) and wanting the best treatment available (n=6). Top reasons to refuse ASCT were: fear of not recovering to baseline (n=2) and prolonged hospital stay (n=2). Oncologists identified using their clinical judgement (n=7), the belief that transplant was the best option (n=7) and lack of medical comorbidities (n=8), as the most important factors when recommending treatment. The lack of high quality randomized controlled trial data (n=9), local guidelines (n=5) and targeted assessment tools (n=7) were identified as barriers to ASCT. Notably, both patients (n=7) and oncologists (n=7) felt that ASCT decision making should not rely on chronological age alone. The findings of the qualitative and quantitative parts of the study concurred with each other and showed similar patterns. Conclusion To our knowledge, our study is the first to analyze contextual factors from the perspective of oncologists and older adults with MM that influence ASCT decision making and utilization. Despite guidelines supporting ASCT efficacy and safety among older adults with MM, our results demonstrate that the decision to undergo ASCT in older adults with MM is complex and variable both from the perspective of the patient and oncologist. Future incorporation of patient decision aids in parallel with enrollment of older adults in ASCT clinical studies and targeted geriatric assessments tools may provide an opportunity to enhance shared decision making and local guideline developments. Disclosures McCurdy: Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Sanofi: Honoraria. Wildes:Carevive Systems: Consultancy; Janssen: Research Funding; Seattle Genetics: Consultancy. Mian:Sanofi: Consultancy; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy; Takeda: Consultancy, Honoraria.

Description: Malaria risk is highly heterogeneous. Understanding village and household-level spatial heterogeneity of malaria risk can support a transition to spatially targeted interventions for malaria elimination. This analysis uses data from cross-sectional prevalence surveys conducted in 2014 and 2016 in two villages (Megiar and Mirap) in Papua New Guinea. Generalised additive modelling was used to characterise spatial heterogeneity of malaria risk and investigate the contribution of individual, household and environmental-level risk factors. Following a period of declining malaria prevalence, the prevalence of P. falciparum increased from 11.4 to 19.1% in Megiar and 12.3 to 28.3% in Mirap between 2014 and 2016, with focal hotspots observed in these villages in 2014 and expanding in 2016. Prevalence of P. vivax was similar in both years (20.6% and 18.3% in Megiar, 22.1% and 23.4% in Mirap) and spatial risk heterogeneity was less apparent compared to P. falciparum. Within-village hotspots varied by Plasmodium species across time and between villages. In Megiar, the adjusted odds ratio (AOR) of infection could be partially explained by household factors that increase risk of vector exposure, such as collecting outdoor surface water as a main source of water. In Mirap, increased AOR overlapped with proximity to densely vegetated areas of the village. The identification of household and environmental factors associated with increased spatial risk may serve as useful indicators of transmission hotspots and inform the development of tailored approaches for malaria control.