PMID- 31349646
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 11
IP  - 8
DP  - 2019 Jul 25
TI  - 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.
LID - 10.3390/cancers11081051 [doi]
LID - 1051
AB  - 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.
FAU - Contaifer, Daniel Jr
AU  - Contaifer D Jr
AD  - Department of Pharmacotherapy and Outcomes Sciences, School of Pharmacy, Virginia 
      Commonwealth University, Richmond, VA 23298, USA.
FAU - Roberts, Catherine H
AU  - Roberts CH
AD  - Department of Internal Medicine, School of Medicine, Virginia Commonwealth 
      University, Richmond, VA 23298, USA.
FAU - Kumar, Naren Gajenthra
AU  - Kumar NG
AUID- ORCID: 0000-0001-7248-6351
AD  - Department of Microbiology, School of Medicine, Virginia Commonwealth University, 
      Richmond, VA 23298, USA.
FAU - Natarajan, Ramesh
AU  - Natarajan R
AUID- ORCID: 0000-0002-3431-9971
AD  - Department of Internal Medicine, School of Medicine, Virginia Commonwealth 
      University, Richmond, VA 23298, USA.
FAU - Fisher, Bernard J
AU  - Fisher BJ
AD  - Department of Internal Medicine, School of Medicine, Virginia Commonwealth 
      University, Richmond, VA 23298, USA.
FAU - Leslie, Kevin
AU  - Leslie K
AD  - Department of Physics, College of Humanities and Sciences, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Reed, Jason
AU  - Reed J
AD  - Department of Physics, College of Humanities and Sciences, Virginia Commonwealth 
      University, Richmond, VA 23284, USA.
FAU - Toor, Amir A
AU  - Toor AA
AD  - Department of Internal Medicine, School of Medicine, Virginia Commonwealth 
      University, Richmond, VA 23298, USA. amir.toor@vcuhealth.org.
AD  - Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, USA. 
      amir.toor@vcuhealth.org.
FAU - Wijesinghe, Dayanjan S
AU  - Wijesinghe DS
AD  - Department of Pharmacotherapy and Outcomes Sciences, School of Pharmacy, Virginia 
      Commonwealth University, Richmond, VA 23298, USA. wijesingheds@vcu.edu.
AD  - Institute for Structural Biology Drug Discovery and Development (ISB3D), VCU 
      School of Pharmacy, Richmond, VA 23298, USA. wijesingheds@vcu.edu.
AD  - Da Vinci Center, Virginia Commonwealth University, Richmond, VA 23284, USA. 
      wijesingheds@vcu.edu.
LA  - eng
GR  - R01 CA185189/CA/NCI NIH HHS/United States
GR  - HD087198/National Institute of Child Health and Human Development/
PT  - Journal Article
DEP - 20190725
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC6721383
OTO - NOTNLM
OT  - graft vs. host disease
OT  - lipidomics
OT  - metabolomics
OT  - risk stratification
OT  - stem cell transplantation
COIS- The authors declare no conflict of interest.
EDAT- 2019/07/28 06:00
MHDA- 2019/07/28 06:01
PMCR- 2019/07/25
CRDT- 2019/07/28 06:00
PHST- 2019/06/16 00:00 [received]
PHST- 2019/07/12 00:00 [revised]
PHST- 2019/07/18 00:00 [accepted]
PHST- 2019/07/28 06:00 [entrez]
PHST- 2019/07/28 06:00 [pubmed]
PHST- 2019/07/28 06:01 [medline]
PHST- 2019/07/25 00:00 [pmc-release]
AID - cancers11081051 [pii]
AID - cancers-11-01051 [pii]
AID - 10.3390/cancers11081051 [doi]
PST - epublish
SO  - Cancers (Basel). 2019 Jul 25;11(8):1051. doi: 10.3390/cancers11081051.