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Cancers (Basel). 2019 Jul 25;11(8). pii: E1051. doi: 10.3390/cancers11081051.

A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature.

Author information

1
Department of Pharmacotherapy and Outcomes Sciences, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
2
Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
3
Department of Microbiology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
4
Department of Physics, College of Humanities and Sciences, Virginia Commonwealth University, Richmond, VA 23284, USA.
5
Department of Internal Medicine, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. amir.toor@vcuhealth.org.
6
Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA. amir.toor@vcuhealth.org.
7
Department of Pharmacotherapy and Outcomes Sciences, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA. wijesingheds@vcu.edu.
8
Institute for Structural Biology Drug Discovery and Development (ISB3D), VCU School of Pharmacy, Richmond, VA 23298, USA. wijesingheds@vcu.edu.
9
Da Vinci Center, Virginia Commonwealth University, Richmond, VA 23284, USA. wijesingheds@vcu.edu.

Abstract

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unrelated donor SCT, or autologous SCT. Blood samples were taken following conditioning and prior to transplant on day 0 and the plasma was comprehensively characterized with respect to its lipidome and metabolome via liquid chromatography/mass spectrometry (LCMS) and gas chromatography/mass spectrometry (GCMS). A pro-inflammatory metabolic profile was observed in patients who eventually developed GVHD. Five potential pre-transplant biomarkers, 2-aminobutyric acid, 1-monopalmitin, diacylglycerols (DG 38:5, DG 38:6), and fatty acid FA 20:1 demonstrated high sensitivity and specificity towards predicting post-transplant GVHD. The resulting predictive model demonstrated an estimated predictive accuracy of risk stratification of 100%, with area under the curve of the ROC of 0.995. The likelihood ratio of 1-monopalmitin (infinity), DG 38:5 (6.0), and DG 38:6 (6.0) also demonstrated that a patient with a positive test result for these biomarkers following conditioning and prior to transplant will be at risk of developing GVHD. Collectively, the data suggest the possibility that pre-transplant metabolic signature may be used for risk stratification of SCT recipients with respect to development of alloreactivity.

KEYWORDS:

graft vs. host disease; lipidomics; metabolomics; risk stratification; stem cell transplantation

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