Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis

Mallory R. Taylor; Steve W. Cole; Joelle Strom; Ruta Brazauskas; K. Scott Baker; Rachel Phelan; David Buchbinder; Betty Hamilton; Hélène Schoemans; Bronwen E. Shaw; Akshay Sharma; Neel S. Bhatt; Sherif M. Badawy; Lena E. Winestone; Jaime M. Preussler; Samantha Mayo; Kareem Jamani; Taiga Nishihori; Michelle A. Lee; Jennifer M. Knight

doi:10.1182/bloodadvances.2023010746

Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis

Mallory R. Taylor, Steve W. Cole, Joelle Strom, Ruta Brazauskas, K. Scott Baker, Rachel Phelan, David Buchbinder, Betty Hamilton, Hélène Schoemans, Bronwen E. Shaw, Akshay Sharma, Neel S. Bhatt, Sherif M. Badawy, Lena E. Winestone, Jaime M. Preussler, Samantha Mayo, Kareem Jamani, Taiga Nishihori, Michelle A. Lee, Jennifer M. Knight

Research output: Contribution to journal › Article › peer-review

Abstract

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.

Original language	English (US)
Pages (from-to)	6830-6838
Number of pages	9
Journal	Blood Advances
Volume	7
Issue number	22
DOIs	https://doi.org/10.1182/bloodadvances.2023010746
State	Published - 2023
Externally published	Yes

ASJC Scopus subject areas

Hematology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1182/bloodadvances.2023010746

Cite this

Taylor, M. R., Cole, S. W., Strom, J., Brazauskas, R., Baker, K. S., Phelan, R., Buchbinder, D., Hamilton, B., Schoemans, H., Shaw, B. E., Sharma, A., Bhatt, N. S., Badawy, S. M., Winestone, L. E., Preussler, J. M., Mayo, S., Jamani, K., Nishihori, T., Lee, M. A., & Knight, J. M. (2023). Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis. Blood Advances, 7(22), 6830-6838. https://doi.org/10.1182/bloodadvances.2023010746

Taylor, MR, Cole, SW, Strom, J, Brazauskas, R, Baker, KS, Phelan, R, Buchbinder, D, Hamilton, B, Schoemans, H, Shaw, BE, Sharma, A, Bhatt, NS, Badawy, SM, Winestone, LE, Preussler, JM, Mayo, S, Jamani, K, Nishihori, T, Lee, MA & Knight, JM 2023, 'Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis', Blood Advances, vol. 7, no. 22, pp. 6830-6838. https://doi.org/10.1182/bloodadvances.2023010746

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title = "Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis",

abstract = "Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.",

author = "Taylor, {Mallory R.} and Cole, {Steve W.} and Joelle Strom and Ruta Brazauskas and Baker, {K. Scott} and Rachel Phelan and David Buchbinder and Betty Hamilton and H{\'e}l{\`e}ne Schoemans and Shaw, {Bronwen E.} and Akshay Sharma and Bhatt, {Neel S.} and Badawy, {Sherif M.} and Winestone, {Lena E.} and Preussler, {Jaime M.} and Samantha Mayo and Kareem Jamani and Taiga Nishihori and Lee, {Michelle A.} and Knight, {Jennifer M.}",

note = "Publisher Copyright: {\textcopyright} 2023 by The American Society of Hematology.",

year = "2023",

doi = "10.1182/bloodadvances.2023010746",

language = "English (US)",

volume = "7",

pages = "6830--6838",

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publisher = "American Society of Hematology",

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TY - JOUR

T1 - Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation

T2 - a CIBMTR analysis

AU - Taylor, Mallory R.

AU - Cole, Steve W.

AU - Strom, Joelle

AU - Brazauskas, Ruta

AU - Baker, K. Scott

AU - Phelan, Rachel

AU - Buchbinder, David

AU - Hamilton, Betty

AU - Schoemans, Hélène

AU - Shaw, Bronwen E.

AU - Sharma, Akshay

AU - Bhatt, Neel S.

AU - Badawy, Sherif M.

AU - Winestone, Lena E.

AU - Preussler, Jaime M.

AU - Mayo, Samantha

AU - Jamani, Kareem

AU - Nishihori, Taiga

AU - Lee, Michelle A.

AU - Knight, Jennifer M.

PY - 2023

Y1 - 2023

N2 - Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.

AB - Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOHs), which can affect health outcomes through the stress response pathway. The conserved transcriptional response to adversity (CTRA) is a stress-mediated proinflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pretransplant CTRA with patient-reported SDOHs in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey and the Functional Assessment of Cancer Therapy–Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among 121 patients, the median age was 54 years, 42% were female, and 91% were White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (P = .003), including the general (P = .003) and BMT-specific (P = .014) components. Effects were driven by the social well-being domain (P = .0001). This corresponded to an 8% to 15% difference in CTRA RNA expression across a 4 standard deviation range in patient-reported SDOHs. Ancillary bioinformatics analyses confirmed the association of well-being with reduced proinflammatory transcription pathway activity [cyclic AMP response element-binding protein, (CREB), NF-κB, and activating protein-1 (AP-1)]. In conclusion, HCT-treated patients who experience unfavorable social conditions show elevated CTRA expression in pretransplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.

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Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis

Abstract

ASJC Scopus subject areas

UN SDGs

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