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Molecular Correlates of Socioeconomic Status and Clinical Outcomes Following Hematopoietic Cell Transplantation for Leukemia.

ABSTRACT: Background:Clinical outcomes among allogeneic hematopoietic cell transplant (HCT) recipients are negatively affected by low socioeconomic status (SES), yet the biological mechanisms accounting for this health disparity remain to be elucidated. Among unrelated donor HCT recipients with acute myelogenous leukemia, one recent pilot study linked low SES to increased expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA) in peripheral blood mononuclear cells, which involves up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I interferon response and antibody synthesis. Methods:This study examined these relationships using additional measures in a larger archival sample of 261 adults who received an unrelated donor HCT for acute myelogenous leukemia to 1) identify cellular and molecular mechanisms involved in SES-related differences in pre-transplant leukocyte transcriptome profiles, and 2) evaluate pre-transplant CTRA biology associations with clinical outcomes through multivariable analysis controlling for demographic-, disease-, and transplant-related covariates. Results:Low SES individuals showed increases in classic monocyte activation and pro-inflammatory transcription control pathways as well as decreases in activation of nonclassic monocytes, all consistent with the CTRA biological pattern. Transplant recipients in the highest or lowest quartiles of the CTRA pro-inflammatory gene component had a more than 2-fold elevated hazard of relapse (hazard ratio [HR]?=?2.47, 95% confidence interval [CI] = 1.44 to 4.24), P?=?.001; HR?=?2.52, 95% CI = 1.46 to 4.34, P?=?.001) and more than 20% reduction in leukemia-free survival (HR?=?1.57, 95% CI = 1.08 to 2.28, P?=?.012; HR?=?1.49, 95% CI = 1.04 to 2.15, P?=?.03) compared with the middle quartiles. Conclusions:These findings identify SES- and CTRA-associated myeloid- and inflammation-related transcriptome signatures in recipient pre-transplant blood samples as a potential novel predictive biomarker of HCT-related clinical outcomes.

SUBMITTER: Knight JM

PROVIDER: S-EPMC6859844 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Molecular Correlates of Socioeconomic Status and Clinical Outcomes Following Hematopoietic Cell Transplantation for Leukemia.

Knight Jennifer M JM Rizzo J Douglas JD Wang Tao T He Naya N Logan Brent R BR Spellman Stephen R SR Lee Stephanie J SJ Verneris Michael R MR Arevalo Jesusa M G JMG Cole Steve W SW

JNCI cancer spectrum 20190912 4

<h4>Background</h4>Clinical outcomes among allogeneic hematopoietic cell transplant (HCT) recipients are negatively affected by low socioeconomic status (SES), yet the biological mechanisms accounting for this health disparity remain to be elucidated. Among unrelated donor HCT recipients with acute myelogenous leukemia, one recent pilot study linked low SES to increased expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA) in p ...[more]

PMID: 31763620

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Project description:PurposeThis study assessed and compared preferences for treatment attributes of maintenance therapies post-hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) and in physicians who treat these patients.Patients and methodsPatients with AML post HSCT and physicians from the United States, United Kingdom, Canada, and Australia (physicians only) completed a web-based discrete choice experiment (DCE). The DCE used inputs identified via a targeted literature review and qualitative interviews to ascertain relevant treatment attributes and associated levels. Six treatment attributes were selected (chance of 2-year relapse-free survival, quality of life [QoL], risk of serious infections, risk of nausea, chance of achieving transfusion independence, and duration of hospitalization annually), each with three or four levels. The experimental design included 36 choice tasks that presented a pair of hypothetical treatment profiles with varying attribute levels; participants chose a preferred treatment for each choice task. Choice tasks were divided into three blocks of 12 tasks each in the patient survey and 4 blocks of 9 tasks each in the physician survey; survey participants were randomly assigned to one of the blocks. Random parameter logit regression models were used to assess the impact of stated attributes on preferences for maintenance treatment post HSCT.ResultsSurveys from 84 patients and 149 physicians were assessed. For patients, QoL was the most important attribute, followed by duration of hospitalization and chance of 2-year relapse-free survival. For physicians, chance of 2-year relapse-free survival was the most important attribute, followed by QoL and risk of serious infections.ConclusionDifferences in how patients and physicians valued post-HSCT maintenance treatment attributes were identified. These differences suggest that patient-centered decision-making may help physicians choose maintenance treatments for patients with AML post HSCT that better meet their treatment needs and improve their treatment satisfaction.

Dataset Information

Molecular Correlates of Socioeconomic Status and Clinical Outcomes Following Hematopoietic Cell Transplantation for Leukemia.

Publications

Molecular Correlates of Socioeconomic Status and Clinical Outcomes Following Hematopoietic Cell Transplantation for Leukemia.

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