PMID- 30949447
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 9
DP  - 2019
TI  - Clinical Metabolomics Identifies Blood Serum Branched Chain Amino Acids as 
      Potential Predictive Biomarkers for Chronic Graft vs. Host Disease.
PG  - 141
LID - 10.3389/fonc.2019.00141 [doi]
LID - 141
AB  - The allogeneic hematopoietic stem cell transplantation procedure-the only 
      curative therapy for many types of hematological cancers-is increasing, and graft 
      vs. host disease (GVHD) is the main cause of morbidity and mortality after 
      transplantation. Currently, GVHD diagnosis is clinically performed. Whereas, 
      biomarker panels have been developed for acute GVHD (aGVHD), there is a lack of 
      information about the chronic form (cGVHD). Using nuclear magnetic resonance 
      (NMR) and gas chromatography coupled to time-of-flight (GC-TOF) mass 
      spectrometry, this study prospectively evaluated the serum metabolome of 18 
      Brazilian patients who had undergone allogeneic hematopoietic stem cell 
      transplantation (HSCT). We identified and quantified 63 metabolites and performed 
      the metabolomic profile on day -10, day 0, day +10 and day +100, in reference to 
      day of transplantation. Patients did not present aGVHD or cGVHD clinical symptoms 
      at sampling times. From 18 patients analyzed, 6 developed cGVHD. The 
      branched-chain amino acids (BCAAs) leucine and isoleucine were reduced and the 
      sulfur-containing metabolite (cystine) was increased at day +10 and day +100. The 
      area under receiver operating characteristics (ROC) curves was higher than 0.79. 
      BCAA findings were validated by liquid chromatography coupled to tandem mass 
      spectrometry (LC-MS/MS) in 49 North American patients at day +100; however, 
      cystine findings were not statistically significant in this patient set. Our 
      results highlight the importance of multi-temporal and multivariate biomarker 
      panels for predicting and understanding cGVHD.
FAU - Alborghetti, Marcos Rodrigo
AU  - Alborghetti MR
AD  - Department of Cell Biology, University of Brasilia, Brasilia, Brazil.
FAU - Correa, Maria Elvira Pizzigatti
AU  - Correa MEP
AD  - Hematology and Hemotherapy Center, Instituto Nacional de Ciencia e Tecnologia do 
      Sangue, University of Campinas, Hemocentro-Unicamp, Campinas, Brazil.
FAU - Whangbo, Jennifer
AU  - Whangbo J
AD  - Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA, United States.
FAU - Shi, Xu
AU  - Shi X
AD  - Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, United 
      States.
FAU - Aricetti, Juliana Aparecida
AU  - Aricetti JA
AD  - Brazilian Bioethanol Science and Technology Laboratory (CTBE)/Brazilian Center 
      for Research in Energy and Materials (CNPEM), Campinas, Brazil.
FAU - da Silva, Andreia Aparecida
AU  - da Silva AA
AD  - Hematology and Hemotherapy Center, Instituto Nacional de Ciencia e Tecnologia do 
      Sangue, University of Campinas, Hemocentro-Unicamp, Campinas, Brazil.
FAU - Miranda, Eliana Cristina Martins
AU  - Miranda ECM
AD  - Hematology and Hemotherapy Center, Instituto Nacional de Ciencia e Tecnologia do 
      Sangue, University of Campinas, Hemocentro-Unicamp, Campinas, Brazil.
FAU - Sforca, Mauricio Luis
AU  - Sforca ML
AD  - Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research 
      in Energy and Materials (CNPEM), Campinas, Brazil.
FAU - Caldana, Camila
AU  - Caldana C
AD  - Brazilian Bioethanol Science and Technology Laboratory (CTBE)/Brazilian Center 
      for Research in Energy and Materials (CNPEM), Campinas, Brazil.
FAU - Gerszten, Robert E
AU  - Gerszten RE
AD  - Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, United 
      States.
FAU - Ritz, Jerome
AU  - Ritz J
AD  - Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA, United States.
FAU - Zeri, Ana Carolina de Mattos
AU  - Zeri ACM
AD  - Brazilian Biosciences National Laboratory (LNBio), Brazilian Center for Research 
      in Energy and Materials (CNPEM), Campinas, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20190318
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC6436081
OTO - NOTNLM
OT  - biomarkers
OT  - bone marrow transplantation
OT  - branched chain amino acids
OT  - cancer
OT  - graft vs. host disease
OT  - mass spectrometry
OT  - metabolomics
OT  - nuclear magnetic resonance
EDAT- 2019/04/06 06:00
MHDA- 2019/04/06 06:01
PMCR- 2019/01/01
CRDT- 2019/04/06 06:00
PHST- 2018/10/18 00:00 [received]
PHST- 2019/02/18 00:00 [accepted]
PHST- 2019/04/06 06:00 [entrez]
PHST- 2019/04/06 06:00 [pubmed]
PHST- 2019/04/06 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2019.00141 [doi]
PST - epublish
SO  - Front Oncol. 2019 Mar 18;9:141. doi: 10.3389/fonc.2019.00141. eCollection 2019.