Sales‐Bonfim, Carmem

Abstract Introduction: Current advances in allogeneic hematopoietic cell transplant (alloHCT) may warrant a paradigm shift in managing children with sickle cell disease (SCD). This study characterizes the clinical outcomes and health care utilization (HCU) of alloHCT for pediatric SCD. We hypothesize that early alloHCT will have improved clinical outcomes, and decreased HCU. Methods: The Center for International Blood and Marrow Transplant Research database was used to identify children 21 years or less with alloHCT for SCD in the United States. Patient data included comprehensive research forms (CRF) from 2000-13 and transplant essential data (TED) forms from 2000-11. CRFs provided clinical risk factors associated with overall survival, graft failure, grade III-IV acute GVHD, and GVHD related event free survival (GREFS) - the survival free of graft failure, chronic GVHD, or death. Risk factors included age, gender, performance status, year of alloHCT, prior SCD complications and therapy, CMV status, donor type, conditioning regimen, and GVHD prophylaxis. Due to low event rates and sample size, only univariate analysis of risk factors was performed. TED data was merged with Pediatric Health Information System (PHIS) inpatient data using a probabilistic merging algorithm to determine risk factors and clinical outcomes associated with HCU. Available PHIS adjusted cost data was used to determine the total adjusted cost for all inpatient admissions per patient per hospital day. To standardize these costs, the total adjusted cost per 30 hospital days was calculated for each patient and used as the primary HCU outcome. HCU outcomes were analyzed for the alloHCT year, day 0 to day +365. Results: CRF data for 161 patients showed an overall survival at 2 years of 90% (95% confidence intervals [CI] 85-95%): 96% (95% CI 89-100%) for related and unrelated cord blood transplant (CBT), 94% (95% CI 86-98%) matched siblings (MSD), and 74% (95% CI 54-90%) matched unrelated donors (MUD, p=0.002). All deaths occurred among children with pre-alloHCT complications of SCD, and deaths were due to organ failure (37.5%), infections (25%), GVHD (6.25%). Risk of death was significantly higher for children ≥10 years old (HR 21, p=0.003) and MUD compared to MSD (HR 5.88, p=0.005) but lower with cyclosporine A (CSA) GVHD prophylaxis versus FK506 (HR 0.33, p=0.031). 75% of deaths occurred before day +42. Cumulative acute GVHD incidence at day 100 was 14% (95% CI 9-20%)and was associated with age ≥10yrs (HR 2.63, p=0.035). Chronic GVHD incidence was 31% (95% CI 23-38%) at 2yrs, and factors associated were age ≥10yrs (HR 1.92, p=0.034), MUD vs MSD (HR 2.53, p=0.017), and CSA vs FK506 prophylaxis (HR 0.48, p=0.018). Chronic GVHD risk increased significantly after 2006 (HR 2.81, p=0.018). The 2yr GREFS was 64% (95% CI 56-71%). Age ≥10yrs (HR 2.2, p=0.005), MUD (vs MSD, HR 3.00, p=0.002) and CSA prophylaxis (vs FK506, HR 0.49, p=0.011) were significantly associated with this outcome. Among the 175 patients with combined TED and PHIS data, the median total adjusted cost was $117,393 per 30 hospital days per patient (range: $36,244-$515,640) during the alloHCT year with a median of 53 hospital days per patient (range: 16-304). Age ≥10yrs and HCU were not significantly associated (p=0.775). MSD had the lowest HCU compared to CBT and unrelated transplants (p<0.001). CBT and peripheral blood stem cells were associated with higher HCU compared to bone marrow (p=0.004). Increased HCU was associated with prior stroke (p=0.0004) and pain crises (p=0.0094) but not acute chest syndrome (p=0.2913). Overall SCD complication and severity indices correlated with increased HCU (p=0.052, p=0.0219, respectively). Conclusions: AlloHCT outcomes in children with SCD were linked to age and donor type suggesting that early alloHCT before age 10 years is preferred. Specifically, SCD severity and MUD alloHCT are associated with poorer outcomes and increased HCU. This supports the recommendation of early alloHCT, prior to onset of SCD complications, for children with SCD and an available MSD. Donor source and type had a significant impact on both outcomes and HCU. CBT outcomes were similar to MSD bone marrow; yet CBT had higher HCU suggesting additional analysis is needed to determine if the clinical benefit outweighs the cost. Further analysis is also needed to better understand and mitigate risk factors associated with poor outcomes and increased HCU following MUD alloHCT. Disclosures Arnold: Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program: Other: award. Hahn:NIH/NHLBI: Research Funding; Novartis: Equity Ownership.

BACKGROUNDTo evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post‐transplantation.METHODSWe analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre‐HCT depression requiring treatment versus those without pre‐HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post‐HCT using Poisson models. We also compared the incidence of grade 2‐4 acute and chronic graft‐versus‐host disease (GVHD) in allogeneic HCT.RESULTSThe study included 1116 (15%) patients with pre‐transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre‐transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04‐1.23; P = 0.004) and a higher incidence of grade 2‐4 acute GVHD (HR, 1.25; 95% CI, 1.14‐1.37; P < 0.0001), but similar incidence of chronic GVHD. 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). There were 512 (13.5%) patients with Pre‐transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre‐transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98‐1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97‐0.99; P = 0.002).CONCLUSIONPre‐transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre‐transplant depression represent a population that is at risk for post‐transplant complications. Cancer 2017;123:1828–1838. © 2017 American Cancer Society.