BackgroundThis study examined patient outcomes using real world data for acute myeloid leukemia (AML) patients initiating treatment.MethodsA retrospective, administrative claims-based, comparative analysis was developed to study outcomes for AML patients initiating treatment with decitabine or azacitidine between January 2006 and June 2012.ResultsTreatment with azacitidine was associated with a longer median overall survival (10.1 versus 6.9 mos., p = 0.007) and a lower risk of hospitalization (HR 0.787, p = 0.02) compared to treatment with decitabine.ConclusionsThis analysis of the outcomes of real-world treatment of AML patients with demethylating agents suggests that azacitidine may result in clinically superior outcomes than decitabine.

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The economic burden associated with acute myeloid leukemia (AML) is poorly defined and understudied. The goal of this study is estimate the direct cost of illness for AML in the United States (US) and the United Kingdom (UK), by conducting a comprehensive literature review and calculating the average direct cost-of-illness per patient for the first 6 months of therapy. Patients were grouped by therapy: intensive chemotherapy alone; induction chemotherapy followed by allogeneic stem cell transplantation (alloSCT); low intensity therapy; and best supportive care. Data suggest that the pathways alloSCT, followed by intensive chemotherapy, are associated with the highest direct costs. Calculated direct costs suggest that they are higher in the US ($14,014 for BSC-only to $352,682 for alloSCT) than in the UK (£3708 [$5837] for BSC-only to £112,545 [$177,187]). AML appears to be associated with significant direct economic costs, but more studies are needed to fully assess the economic impact especially in relation to total and indirect costs.

This study utilized claims data from a national US commercial health insurer to examine rates of cytopenia-related complications (significant bleeding, infection) and health care utilization (emergency room visits, inpatient hospitalizations) among patients with myelodysplastic syndromes (MDS) within predefined periods of transfusion activity and active therapy. Periods with no transfusions, regardless of relationship to treatment intervention, were associated with lower rates of cytopenia-related complications. These data suggest that eliminating or reducing the need for transfusions may help to reduce MDS-related medical problems, and treatment toward that goal should be considered in patients with MDS needing transfusions.

3614 Background: Acute Myeloid Leukemia (AML) is a common form of leukemia in adults and often requires high resource use. About 84% of the total cost is attributed to hospital payments (Menzin 2002). The aggregate disease burden is difficult to estimate due to multiple complications and treatment courses. The standard treatment modality for AML is intensive chemotherapy with complete remission (CR) achieved in up to 60% of adults with de novo AML who are less than 70 years old (Tallman, 2005), while in the older adults CR rates occur in approximately 45% (Jabbour, 2006). For patients who relapse after CR there are a limited number of efficacious therapeutic options. These include best supportive care (BSC), additional cycles of chemotherapy and stem cell transplantation (SCT) in a minority of patients. Aim: To estimate the economic burden of the total treatment costs of AML in patients receiving therapy in the US and UK. Treatment costs are specifically assessed for induction therapy (IT), consolidation therapy (CT), for follow up during CR, and salvage therapy for relapsed or refractory disease. Methods: To identify the total costs of AML therapy, a systematic literature review was conducted of standard treatments employed during the past 5 years. Economic costs were estimated per course of treatment which included IT, CT, supportive treatment during CR, and salvage therapy including use of SCT. The total economic burden was calculated combining cost per patient with epidemiology data. Incidence rates for the US and UK and treatment outcome probabilities were calculated from the Surveillance Epidemiology and End Results (SEER), Eurostat and peer reviewed literature. Unit costs were identified using publicly available databases. Calculations were conducted for younger (<65) and older (>65) patients given differences in incidence rates identified between these groups. Costs of treatment were calculated individually for each of the following treatment stages: 1) IT (standard dose chemotherapy (SDC) 1 cycle), 2) CT- 2 cycles of chemotherapy 3) follow up after CR (costs of BSC – 6 cycles), and 4) salvage therapy for relapse refractory disease. Results: The costs associated with hospitalization are the main component in all treatment stages (induction, consolidation, and relapse) ranging from 66% to 92% of the total costs. IT plus CT accounted for 19%-91% of the total cost per patient. When combining costs per patient with incidence data, it is estimated that the total economic burden of AML treatment ranges from £13 mln for population >65 and £38 mln for the <65 in the UK and approx. $0.5 billion and $1.5$ billion respectively in US. Not surprising, the cost of transplantation was the highest of all the treatments. The financial burden after relapse is also high compared to the cost of being followed in CR (which consists primarily of the laboratory monitoring and supportive care), namely £683 for BSC, £4,097 for chemotherapy and £82,262 transplantation vs. £4,097 in CR in the UK and $2,477, $56,588 and $154,739 vs. $14,861, respectively in the US. (Table 1). Summary/Conclusions: The economic burden of AML treatment is very high. In both the UK and US, hospitalization costs are the key drivers. Findings suggest that savings to the healthcare system could be achieved by sustaining CR status for longer periods. When relapse occurs, high costs are incurred again, particularly when another round of chemotherapy is given. Therefore, besides the fact that achieving and staying in CR is important from the clinical point of view, it has an essential justification from the economic perspective when considering the costs that patients incur after relapse. It is critical to focus on developing new therapies that can prevent relapse and maintain AML patients' CR status to maximize their survival. Disclosures: Mahmoud: celgene: Employment. Skikne:Celgene: Employment, Equity Ownership. Kucmin-Bemelmans:Pharmerit BV: Employment. Alleman:Pharmerit BV: Employment. Hensen:Pharmerit BV: Employment.

3837 Background: Lenalidomide (LEN) was approved in the U.S. in December, 2005 for patients (pts) with transfusion-dependent (TD) anemia due to low- or intermediate-risk myelodysplastic syndromes (MDS) associated with a deletion 5q (del5q). In this patient population, Phase 2 clinical trial evidence indicates that 2/3 of TD pts achieved transfusion independence (TI), with 90% of pts achieving transfusion benefit by 3 months. This observational study examines LEN treatment patterns and association with reduced transfusion needs in a Medicare-enrolled population with MDS. Methods: MDS pts from 2006–8were identified using ICD-9 CM codes from 100% Medicare claims. Claims data from 2005–2008 were linked to Medicare enrollment files, and zip code-level measures of income and education from the 2000 U.S. Census. The study cohort consisted of MDS pts enrolled in Medicare Parts A and B and without Medicare Advantage (HMO enrollment) from 12 months before MDS diagnosis, and enrolled in Part D from diagnosis forward, allowing for observation of oral drug use. Patients were followed until death or end of study. LEN use was identified from Part D event files based on National Drug Code. Claims data were used to calculate duration, daily dose, time to initiation of treatment, and relationship to erythropoiesis-stimulating agents (ESAs) and hypomethylating agents (HMAs) use. Transfusion status was evaluated each week (wk), based on receipt of transfusions during the current and preceding 7-wk period (rolling). TD required transfusions during 2 of the 8 wks, separated by at least 3 wks. TI required a period of 8 wks without transfusions. An intermediate transfusion user (TU) category received 1 transfusion during the prior 8 wks. Change in transfusion status during a treatment episode was examined. Bivariate analyses examined sample means and proportions, overall and by MDS risk group defined based on initial diagnostic codes. Results: The cohort of 22,480 pts was predominantly white (88%) and female (58%), and 76% were age 75 years or older. MDS risk group was ICD-9 coded as 456 (2%) del5q, 5,989 (27%) other lower-risk, 1,277 (6%) higher-risk and 14,758 (75%) not otherwise specified (NOS). LEN use rates were 3% (n=716) overall, with 31% of del5q, 3% of other lower-risk, 5% of higher-risk and 2% of MDS NOS receiving therapy. Median time to initiate LEN (11.5 wks, range 0–132) was less for del5q (8 wks) than for other lower-risk coded patients (20 wks); most (86%) del5q pts and nearly all other lower-risk pts (96%) received ESAs prior to LEN. Pts received a mean of 4.1 4-wk cycles of LEN (median=2); 53% received <3 cycles. Multivariate analysis indicated that LEN initiation was negatively associated with older age, poor performance status, and baseline diabetes, stroke, and renal disease, and positively associated with del5q risk group and baseline pancytopenia and thrombocytopenia. At LEN initiation 36% were TI, 31% TU and 33% TD. Point estimates indicate that 44% of pts who were either TU or TD at LEN initiation (53% of del5q) experienced a reduction in transfusion use. Among those TD at LEN initiation, 45% reduced transfusion use during treatment, while 15% achieved TI. 43% of pts TU at LEN initiation achieved TI status. When limited to patients with ≥3 cycles, 71% of pts who were TU or TD at LEN initiation (83% of del5q) experienced reduced transfusion use. 77% of TD patients reduced transfusion use during treatment, and 40% achieved TI. Finally among these patients who were TU at LEN initiation, 67% became TI. Small sample sizes provided inadequate power to detect differences between MDS risk groups. Conclusions: This large population-based observational study of LEN use in Medicare-enrolled MDS pts showed that use rates were highest among del5q pts, as expected. Older pts were less likely than younger pts to receive LEN treatment. Shorter time to initiation of LEN for del5q vs. lower-risk pts indicates that physicians more promptly prescribe LEN for those with del5q. Response rates for the full cohort reflected the mix of risk groups and relatively short duration of therapy for many pts, but overall were consistent with published clinical trials. Response rates were higher when at least 3 cycles of therapy were received, underscoring the need to sustain therapy to achieve therapeutic response. Disclosures: Gore: Celgene Corporation: Consultancy, Research Funding. Baer:Novartis, Inc.: Research Funding; Celgene, Inc.: Research Funding. Mahmoud:celgene: Employment. Davidoff:Novartis: Research Funding; Celgene: Equity Ownership, Research Funding; National Institutes of Health: Research Funding; GlaxoSmithKline: Research Funding.

Despite the widespread use of highly active antiretroviral therapy, cryptococcal meningoencephalitis has emerged as the second leading cause of infectious morbidity and mortality in HIV-infected patients worldwide. It presents usually as subacute or chronic disease but occasionally may be fulminant. Common clinical presentations included headache, fever, and depressed level of consciousness. The infection affects both the subarachnoid space and brain parenchyma, and is characterized by a paucity of inflammation and a large fungal burden in the cerebrospinal fluid at the time of diagnosis. Infection is usually lethal without treatment, thus the prompt diagnosis and therapy might improve the outcome. We report a case of brain death caused by Cryptococcus neoformans meningitis that was diagnosed based on clinical neurological examinations and supported by the absence of cerebral blood flow on brain angiography.

This study demonstrates the quantitative characteristics of the first patient‐reported outcome (PRO) tool developed for patients with nontransfusion‐dependent β‐thalassemia (NTDT), the NTDT‐PRO©. A multicenter validation study was performed over 24 weeks, involving 48 patients from Italy, Lebanon, Greece, and Thailand. Most patients were female (68.8%), with a median age of 34.5 years (range, 18‐52); 66.7% were diagnosed with β‐thalassemia intermedia, and median time since diagnosis was 22 years (range, 0‐43). The NTDT‐PRO comprises 6 items across 2 domains (Tiredness/Weakness and Shortness of Breath [SoB]), and was valid and reliable, with good consistency. At baseline, most patients reported symptoms as present via the NTDT‐PRO, and were highly compliant, ≥90% completing the NTDT‐PRO tool. In a pairwise correlation analysis, all items were positively correlated. Correlations between NTDT‐PRO and existing tools—36‐Item Short Form Health Survey version 2 (SF‐36v2) and Functional Assessment of Cancer Therapy‐Anemia (FACT‐An)—were assessed at weeks 1, 3, and 12; robust correlations were seen between SoB and SF‐36v2‐Vitality (rs = −0.53), and between SoB and Fact‐An‐Fatigue Experience (rs = −0.66) at week 1. Internal consistency was high for both Tiredness/Weakness (Cronbach alpha, 0.91) and SoB (Spearman‐Brown coefficient, 0.78); intraclass correlation coefficients were high (Tiredness/Weakness, 0.88 and 0.97; SoB, 0.92 and 0.98), demonstrating stability. Further studies are required to fully support the validity of this tool, this study demonstrated the usefulness of the NTDT‐PRO in the clinical setting and for longitudinal clinical research, particularly in trials where patient health‐related quality of life is expected to change.