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Depression prior to HSCT linked to increased mortality, GVHD risk
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ORLANDO, Fla. — A depression diagnosis prior to allogeneic hematopoietic stem cell transplantation appeared associated with a greater risk for acute graft-versus-host disease and mortality, according to results from a retrospective study presented at the ASH Annual Meeting and Exposition.
Pre-transplant depression also appeared associated with longer hospital stays during the first 100 days following autologous or allogeneic transplantation.
Areej R. El-Jawahri
“Depression has been associated with increased morbidity and mortality in various medical conditions including cancer, cardiovascular disease and stroke,” Areej R. El-Jawahri, MD, an oncologist and assistant in medicine at Massachusetts General Hospital Cancer Center and an instructor in medicine at Harvard Medical School, said during her presentation. “However, the impact of the diagnosis of depression prior to allogenic stem cell transplant on OS has actually yielded conflicting results.
“Defining the effect of pre-transplant depression on these outcomes can have important clinical implications on the way we manage and prevent disease in this patient population,” El-Jawahri added.
Using data from the Center for International Blood and Marrow Transplant Research registry, El-Jawahri and colleagues compared groups of patients who underwent allogeneic or autologous hematopoietic stem cell transplantation (HSCT) between 2007 and 2012.
In the allogeneic group, 6,317 patients (85%) made up the control cohort, and 1,116 patients (15%) were diagnosed pre-transplant with depression. The patients diagnosed with depression were more likely to be women, white, divorced, less educated, not working full-time, had more comorbidities and a lower performance status.
Results of a multivariable analysis showed depression increased the risk for mortality (HR = 1.13; 95% CI, 1.04-1.23) and grade 2 to grade 4 acute graft-versus-host disease (GVHD; HR = 1.25; 95% CI, 1.14-1.37). Further, there was an association between depression and fewer days alive while not hospitalized (means ratio [MR] = 0.97; 95% CI, 0.95-0.99).
Among patients who underwent autologous HSCT, 3,274 patients (86.5%) did not have depression and 512 patients (13.5%) had a depression diagnosis. Those diagnosed with depression had similar characteristics as those with depression in the allogeneic arm and additionally, tended to be younger.
Depression did not appear associated with OS in this cohort. However, there was a significant association between depression and fewer days alive while not hospitalized (MR = 0.98; 95% CI, 0.97-0.99).
“These findings highlight the impact of a history of depression on important patient outcomes after stem cell transplantation,” El-Jawahri told HemOnc Today. “This information helps us identify patients with history of depression prior to transplantation as a population at risk for future complications. We can then test whether providing them with additional supportive and psychological interventions can help improve their outcomes after transplantation.” – by Anthony SanFilippo
Reference:
El-Jawahri A, et al. Abstract 265. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.
Disclosure: The researchers report research funding from NIH/NHLBI and Regimmune, consultant/advisory roles with Bristol-Myers Squibb and Kadmon, and stock or other ownership in Novartis.
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Marco Mielcarek, MD
This analysis included a fairly large sample size of more than 10,000 patients who had hematopoietic cell transplants. Approximately two thirds had allogeneic transplants and one third had autologous transplants. While 85% of patients did not have depression, 15% had depression before transplant requiring treatment.
The researchers found that pretransplant depression increased the relative mortality risk after allogeneic transplantation by 16%. The question is whether depression was causing the increased mortality, or whether it was merely a marker of something else driving mortality? For instance, depression could be associated with poor adherence to medications after a transplant, such as immunosuppressive medications that are important after allogeneic transplantation to protect patients from graft-versus-host disease (GVHD). The researchers also showed that pretransplant depression was associated with a 24% relative risk increase for acute GVHD. It is possible that patients with depression are less compliant with their posttransplant immunosuppressive regimens, which could translate into increased risks for acute GVHD and mortality.
The alternative explanation is that depression could be a surrogate marker for other unrecognized factors driving mortality. For example, depression could be a marker for greater comorbidity or worse performance status. Patients might be depressed because they were not doing well before the transplant. Although the researchers adjusted for comorbidity and performance status in multivariate analyses, one could argue that one cannot account for all potential confounders in a retrospective study. Thus, there may be additional factors unaccounted for that could have been driving the association between depression and mortality. Finally, depression in this study was defined as requiring medications to treat depression. Could there be any drug–drug interactions between anti-depression medications and immunosuppressive mediations that might have compromised GVHD protection? In summary, this is a thought-provoking study drawing attention to the possible impact of pretransplant depression on important outcomes after allogeneic hematopoietic cell transplantation. depression medications and immunosuppressive mediations that make that not quite as effective.
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