Bonfim, Carmem

Abstract Acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) are the two most common childhood leukemias. Novel drug therapies and allogeneic hematopoietic cell transplant (alloHCT) have improved ALL and AML treatment outcomes over the past two decades. However, alloHCT may be associated with significant morbidity and mortality that results in increased healthcare utilization. To date, no multi-center comparative effectiveness studies have been performed specifically evaluating alloHCT in children with ALL or AML. This study uses a novel methodology to investigate the hypothesis that matched sibling donor (MSD) alloHCT has significantly lower healthcare utilization compared to unrelated donor (URD) and that among URD, umbilical cord blood transplants (CBT) will have higher initial utilization but lower long-term utilization. Clinical and transplant outcomes data from the Center for International Blood and Marrow Transplant Research (CIBMTR) database were merged with inpatient resource utilization and standardized cost data from the Pediatric Health Information System (PHIS) database using a probabilistic merge methodology. This merged dataset contained U.S. patients age 1-21 years who received alloHCT for ALL or AML from 2004-2013 with comprehensive CIBMTR data at a PHIS reporting hospital. The primary outcomes of overall survival (OS), leukemia free survival (LFS), and inpatient resource utilization were evaluated using Kaplan-Meier analysis, Cox proportional hazards, and unadjusted Poisson regression analysis. Cost and resource comparisons for all donor types were made through day+100 and focused on URD only comparisons up to 2-year follow-up. Donor procurement costs were not directly included in this analysis. A total of 797 patients (54% of CIBMTR eligible patients and 89% of CIBMTR patients at PHIS centers) were successfully identified in both CIBMTR and PHIS; 433 had ALL and had 364 AML. LFS for ALL at 3 years was 68% for MSD, 53% for MUD, and 53% for CBT. The LFS in ALL was significantly impacted by donor type, age, disease status, and CMV (Table). The associated total costs were significantly higher for well-matched unrelated bone marrow (MUD) vs MSD at 100d ($246,149 vs $147,547, p<0.01), but CBT costs were not significantly higher compared to MUD at 100d ($275,673 vs $246,149, p=0.09). When median total costs per day were compared across donor source, findings were similar with well- MUD was significantly higher than MSD at 100d ($3,388/d vs $2,511/d, p=0.012), and no significant difference between CBT and MUD ($3,881/d vs $3,388/d, p=0.53). The corresponding average length of stay (ALOS) was 35 days for MUD, 34 days MSD, and 53 days CBT. Among URD alloHCT, median CBT costs per day were not significantly higher compared to MUD at 2yrs ($2,472/d vs $2,294/d, p=0.49). AlloHCT for AML had a 3-yr LFS of 56% for MSD, 46% for MUD, and 41% for CBT. LFS were significantly different by disease status and performance status (Table). The associated total costs were significantly higher for MUD at 100d than MSD ($259,293 vs $143,870, p<0.001), but CBT costs were not significantly higher compared to MUD at 100d ($301,160 vs $259,293, p=0.055). Comparisons of median total costs per day were similar, MUD vs MSD at 100d was significantly higher ($3,627/d vs $2,478/d, p<0.01), but CBT costs were not significantly higher compared to MUD at 100d ($3,891/d vs $3,627/d, p=0.95). The corresponding ALOS was 38 days for MUD, 35 days MSD, and 66 days CBT. Among URD alloHCT, median CBT costs per day were not significantly higher compared to MUD at 2yrs ($3,232/d vs $3,102/d, p=0.49). This study recapitulates previously published outcomes of alloHCT for acute leukemia AND adds key findings on the impact of alloHCT on inpatient resource utilization and costs. Specifically, MSD and MUD alloHCT provide similar survival outcomes; however, MSD alloHCT has a significant advantage in cost and resource utilization for both ALL and AML. Among URD transplants, CBT does not show any substantial survival or resource utilization advantage over MUD. Ongoing research will need to be performed to determine if the difference among URD alloHCT becomes significant with a larger sample size and/or beyond the 2 years following alloHCT. Table Table. Disclosures Pulsipher: Novartis: Consultancy, Other: Study Steering Committee; Jazz Pharmaceutical: Consultancy; Medac: Other: Housing support for conference; Chimerix: Consultancy. Hahn:Novartis: Equity Ownership; NIH: Research Funding.

Abstract Introduction: Depression is associated with increased mortality among healthy individuals and patients with various medical conditions including cardiovascular disease and cancer. The impact of an existing diagnosis of depression prior to autologous and allogeneic hematopoietic stem cell transplantation (HCT) on clinical outcomes including overall survival has not been studied. Methods: We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to compare overall survival and hospital-length-of-stay during the first 100 days after autologous (n= 3786) or allogeneic (n = 7433) HCT for adult (≥ 18 years) patients with hematologic malignancies with an existing diagnosis of pre-transplant depression requiring treatment vs. those without pre-transplant depression. Data regarding an existing diagnosis of pre-transplant depression requiring treatment were collected from medical chart reviews and reported to the CIBMTR. Data for autologous and allogeneic HCT were analyzed separately. Using Cox proportional hazards regression models adjusting for patient-, disease-(including the disease risk index for allogeneic HCT), donor-(for allogeneic HCT), and transplant-related variables, we compared overall survival between patients with or without pre-transplant depression. To account for early deaths, we compared the number of days alive and out of the hospital in the first 100 days post-transplantation using Poisson models adjusting for patient-, disease-, and transplant-related variables. Among patients undergoing allogeneic HCT, we also compared the risk of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD among patients with or without pre-transplant depression using Cox proportional hazard regression analyses controlling for significant confounders. Results: We included 1116 (15%) patients with pre-transplant depression and 6317 (85%) patients without pre-transplant depression who underwent allogeneic HCT between 2008 and 2012. Patients with pre-transplant depression were similar to those without pre-transplant depression with regards to age, disease distribution, disease risk index, time from diagnosis to transplant, conditioning regimen, receipt of total body irradiation, graft type, donor type, and donor source, but they were more likely to be female, white, divorced, less educated, not working full-time, and had lower performance status and higher number of comorbid conditions. In multivariable analyses, pre-transplant depression was associated with higher overall mortality (HR 1.13, 95% CI 1.04-1.23, p = 0.004) and higher risk of grade II-IV acute GVHD (HR 1.25, 95%CI 1.14-1.37, p < 0.0001), but similar risk of chronic GVHD (HR 1.06, 95% CI 0.96-1.16, p = 0.26). Pre-transplant depression was associated with fewer days alive and out-of-the hospital (Means Ratio (MR) = 0.97, 95% CI 0.95-0.99, P = 0.004). Among patients undergoing autologous HCT, we included 512 (13.5%) patients with pre-transplant depression and 3274 (86.5%) patients without pre-transplant depression between 2007 and 2012. Patients with pre-transplant depression were similar to those without pre-transplant depression with regards to disease distribution, disease status prior to HCT, time from diagnosis to transplant, conditioning regimen, and year of transplant, but they were slightly younger, more likely be to female, white, divorced, less educated, not working full-time, and had lower performance status and higher number of comorbid conditions. Pre-transplant depression in autologous HCT recipients was not associated with overall survival in multivariable analyses (HR 1.15, 95% CI 0.98-1.34, p = 0.096), but was significantly associated with fewer days alive and out of the hospital (MR = 0.98, 95% CI 0.97-0.99, p = 0.002). Conclusion: Pre-transplant depression was associated with higher mortality and higher risk of acute GVHD among patients undergoing allogeneic HCT. Moreover, pre-transplant depression is associated with a longer hospital-length-of stay during the first 100 days after autologous and allogeneic HCT. Therefore patients with pre-transplant depression represent a highly vulnerable population at risk for post-transplant mortality and complications, and they may benefit from more intensive interventions to mitigate the risk of depression on their post-transplant outcomes. Disclosures Chen: Bayer: Consultancy, Research Funding. Lee:Bristol-Myers Squibb: Consultancy; Kadmon: Consultancy. Hahn:Novartis: Equity Ownership; NIH/NHLBI: Research Funding.

Abstract Introduction: Allogeneic stem cell transplant is an intensive procedure, offered in a limited number of medical centres. We sought to describe how sociodemographic variables impacted access to transplant across the United States, and if disadvantaged populations had inferior access to transplant. Methods: Data from the Surveillance, Epidemiology and End Results Program (SEER) and the Center for International Blood and Marrow Transplant Research (CIBMTR) was integrated to determine the rate of unrelated donor transplantation between 2000 and 2010 in each of the 612 counties included in the SEER registry. Patients under the age of 65 with AML, ALL, and MDS were included, and the analysis was restricted to unrelated donors due to limited availability of ZIP code in CIBMTR data. New incident cases were determined from SEER, and the number of transplants was determined from CIBMTR. The transplant rate was calculated (transplants performed divided by incident cases) for each county. County attributes (percent minority, rural/urban status, percentage below the poverty line, and median family size) were obtained from US Census data. Poisson regression was used to describe how county attributes impacted transplant rates. Transplant rates were calculated separately for AML, White residents, and pediatric ALL. Results: 3147 patients were identified in the CIBMTR dataset that met inclusion criteria. The estimated ZIP code completeness was 75%. There were 30,468 new incident diagnoses of ALL, AML, and MDS. For AML, patients from rural areas (less than 20,000 residents) and patients from areas with higher poverty levels had lower transplant rates (Table 1). Minority status and family size did not impact transplant rate. In regression models, higher levels of poverty remained associated with lower transplant rates, while rurality did not (Table 2). The results were similar among White residents. In contrast, in pediatric ALL, no county attributes (poverty, rurality, percent minority, and family size) were significantly associated with a difference in transplant rate (Table 1). However, numbers of transplants were smaller, limiting power. Discussion: Patients with AML from disadvantaged areas had lower rates of unrelated donor transplant. While patients from disadvantaged areas were also more likely to be non-White, and non-White Americans are less likely to have an available unrelated donor, this difference was also seen in White Americans from disadvantaged areas. This suggests the lower transplant rate is due impaired access to transplant. Poverty rate was the most important predictor of transplant rate. The results of this study suggest that improving access to transplant in disadvantaged populations should be a priority for health care administrators. Based on these results, approximately 2500 Americans do not undergo allogeneic transplant annually due to inferior access associated with higher poverty rates. Table 1 Univariate Analysis Table 1. Univariate Analysis Table 2 Acute Myeloid Leukemia, Regression Model * Metropolitan = county > 50,000 people, micropolitan = county > 20,000, rural county < 20,000. Table 2. Acute Myeloid Leukemia, Regression Model. / * Metropolitan = county > 50,000 people, micropolitan = county > 20,000, rural county < 20,000. Disclosures Hahn: Novartis: Equity Ownership; NIH: Research Funding.