Clinical Outcomes Among Unrelated Donor Transplant Recipients for Acute Myelogenous Leukemia As a Function of Socioeconomic Status and Related Transcriptome Differences

Background: Low socioeconomic status (SES) is associated with worse overall survival (OS) and higher transplant-related mortality (TRM) in unrelated donor (URD) hematopoietic stem cell transplantation (HCT) recipients (BBMT 2009, 15:1543). A homogeneous subset of patients from the parent study was selected and consisted of URD myeloablative (MA) HCT recipients transplanted for acute myelogenous leukemia (AML) in first complete remission (CR1). Among this group, low SES was significantly associated with increased expression of the conserved transcriptional response to adversity (CTRA) gene expression profile, previously identified as also overexpressed in other populations under conditions of chronic stress or adversity. The purpose of the current study is to identify whether increased CTRA gene expression may be an immunobiologic mechanism by which pre-existing factors, such as SES, may impact HCT outcomes.

Methods: We analyzed whether low vs. high expression of the CTRA gene profile (53 inflammatory, interferon-related, and antibody-related genes) in peripheral blood mononuclear cells (PBMCs) from a population of 78 Caucasian individuals between ages 20-59 who received an URD MA HCT for AML in CR1 is associated with significantly different clinical outcomes. We used the Kaplan-Meier method to assess association with leukemia free survival (LFS) and OS and the cumulative-incidence function method to assess the association with neutrophil engraftment, acute and chronic graft-versus-host disease, TRM, and relapse. Patient, disease, and HCT-related characteristics were compared by chi-square statistic for categorical variables and the Kruskal-Wallis test for continuous variables.

Results: Increased expression of the CTRA gene profile is associated with increased relapse at 3 years post-HCT (p=.04; Figure 1) and decreased LFS overall (p=.04; Figure 2). There were no significant outcome differences based on SES in this sample. HCT recipients of high SES lived closer to the transplant center (p<.001) while recipients with higher CTRA gene expression profiles were younger (p=.04) and were infused with lower doses of peripheral blood cells (p.02). All other patient, disease, and demographic variables were equal between groups.

Conclusions: Exposure to socioeconomic adversity is associated with a marked pro-inflammatory/anti-antiviral shift in the PBMC transcriptome and this shift in gene expression is reciprocally related to adverse clinical outcomes including increased relapse and decreased LFS.

Figure 1. Cumulative incidence of relapse by CTRA gene profile

Figure 2. Probability of leukemia free survival by CTRA gene profile