The Impact of Pre-Transplant Depression on Outcomes of Allogeneic and Autologous Hematopoietic Stem Cell Transplantation
Authors: El-Jawahri Areej , Chen Yi-Bin , Brazauskas Ruta , He Naya , Lee Stephanie J. , Knight Jennifer M , Hahn Theresa , Khera Nandita , Dalal Jignesh D , Bonfim Carmem , Atsuta Yoshiko , Saber Wael 
Published: October 2019

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.