Impact of pre-transplant anxiety and depression on outcomes of AML patients after allogeneic transplantation

Abstract Introduction: Allogeneic stem cell transplantation (Allo-SCT) in Acute Myeloid Leukemia (AML) is an important part of the treatment paradigm for those who are eligible for transplantation. Depression and anxiety symptoms are commonly seen prior to Allo-SCT. Prior studies suggest that patients with depression pre-transplant have shorter survival and worse outcomes. This retrospective study investigated the impact of pre-transplant depression and anxiety on outcomes of AML patients status post (s/p) Allo-SCT. Methods: A retrospective review included 115 adult patients with AML s/p Allo-SCT from 2022 to 2024 at the University of Kansas Medical Center. Our bone marrow transplant program includes an embedded psychology-oncology team with 2 FTEs. Trainees are also available who help with inpatient and outpatient evaluations. This team rounds with the leukemia and transplant teams and formally evaluates all patients prior to allo-SCT. Assessments for depression, anxiety, and cognitive function are completed during the pre-transplant evaluation. Severity of depression, anxiety and cognitive function were evaluated using the patient health questionnaire-9 (PHQ-9), general anxiety disorder- 7 (GAD-7) and the Montreal Cognitive Assessment (MoCA). These scores were thus available on chart review, and the most recent scores prior to transplant were recorded. PHQ-9 score of 0-4 indicated no depression, 5-9 mild depression, 10-14 moderate depression, 15-19 moderately severe depression, and 20+ severe depression. GAD-7 score of 0-4 indicated no anxiety, 5-9 mild anxiety, 10-14 moderate anxiety, 15+ severe anxiety on GAD-7. MoCA assessment for cognitive function indicated normal (score of 26+) or cognitive impairment of mild (18-25), moderate (10-17) or severe (<10) degree. The Kaplan-Meier model was used to evaluate overall survival. Survival outcomes were compared using the log-rank test. For continuous independent variables, comparisons of mean responses were assessed using an independent two-sample t-test or multiple linear regression, as appropriate. To evaluate associations between categorical independent variables and baseline characteristics, Pearson's Chi-squared test was used. Results: Most patients were white/Caucasian (90%), median age was 61 years old (20-75) and 51% were males. Most common AML subtype was AML with mutated NPM1 (21.4%), and majority were in CR1 prior to transplant (70.7%). The median PHQ-9 score was 3 (0-17) and GAD-7 score was 1 (0-16). 24% had mild depression, 9.5% had moderate depression, 1.7% had moderately severe depression, and 65% had no depression. No severe depression was seen. 14% had mild anxiety, 7.8% had moderate anxiety, 1.7% had severe anxiety, and 77% had no anxiety. 27% of patients were on an anti-depressant/anti-anxiety agent 30 days prior to allo-SCT. The estimated 3-year overall survival (OS) for the total population was 72% (95% CI 63-84) and progression free survival (PFS) was 67% (95% CI 53-85). The most common cause of death was disease progression. When comparing patients by the severity of depression, anxiety and cognitive impairment, there was no significant association in OS (p= 0.52, 0.63, 0.50 respectively). This was similarly seen in PFS when comparing patients by their severity of depression, anxiety and cognitive impairment (p= 0.72, 0.12, 0.06). No association was seen between grade of aGVHD and severity of depression, anxiety, and cognitive impairment (p= 0.47, 0.82, 1.0 respectively). However, there was an association seen between depression severity and having any grade aGVHD (p=0.041). Conclusion: Although prior literature has suggested worse outcomes with patients with depression prior to allo-SCT, our retrospective study does not support this. Increased severity of depression, anxiety or cognitive impairment did not translate to worse outcomes. This could be due to the extensive support from psycho-oncology evaluation, intervention and recommendations, as having a dedicated psychology-oncology team for BMT is uncommon. An association between incidence of aGVHD and severity of depression was seen, which could be an area of further investigation and improvement. Our data suggests that the presence of anxiety and/or depression should not exclude a patient from proceeding with allo-SCT.