The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease.
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
10 12 2019
10 12 2019
Historique:
received:
02
08
2019
accepted:
19
09
2019
entrez:
10
12
2019
pubmed:
10
12
2019
medline:
23
9
2020
Statut:
ppublish
Résumé
The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP), derived from 2 serum biomarkers, measures damage to crypts in the gastrointestinal tract during graft-versus-host disease (GVHD). We hypothesized that changes in MAP after treatment could validate it as a response biomarker. We prospectively collected serum samples and clinical stages of acute GVHD from 615 patients receiving hematopoietic cell transplantation in 20 centers at initiation of first-line systemic treatment and 4 weeks later. We computed MAPs and clinical responses and compared their abilities to predict 6-month nonrelapse mortality (NRM) in the validation cohort (n = 367). After 4 weeks of treatment, MAPs predicted NRM better than the change in clinical symptoms in all patients and identified 2 groups with significantly different NRM in both clinical responders (40% vs 12%, P < .0001) and nonresponders (65% vs 25%, P < .0001). MAPs successfully reclassified patients for NRM risk within every clinical grade of acute GVHD after 4 weeks of treatment. At the beginning of treatment, patients with a low MAP that rose above the threshold of 0.290 after 4 weeks of treatment had a significant increase in NRM, whereas patients with a high MAP at onset that fell below that threshold after treatment had a striking decrease in NRM that translated into clear differences in overall survival. We conclude that a MAP measured before and after treatment of acute GVHD is a response biomarker that predicts long-term outcomes more accurately than change in clinical symptoms. MAPs have the potential to guide therapy for acute GVHD and may function as a useful end point in clinical trials.
Identifiants
pubmed: 31816061
pii: 429584
doi: 10.1182/bloodadvances.2019000791
pmc: PMC6963240
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4034-4042Subventions
Organisme : NCI NIH HHS
ID : P01 CA039542
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA196521
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR001434
Pays : United States
Informations de copyright
© 2019 by The American Society of Hematology.
Références
Lancet. 2009 May 2;373(9674):1550-61
pubmed: 19282026
Blood. 2010 Jul 1;115(26):5412-7
pubmed: 20388871
Blood. 2011 Dec 15;118(25):6702-8
pubmed: 21979939
Bone Marrow Transplant. 2014 Jul;49(7):966-71
pubmed: 24777184
Biol Blood Marrow Transplant. 2009 Jul;15(7):777-84
pubmed: 19539208
Biol Blood Marrow Transplant. 2002;8(7):387-94
pubmed: 12171485
Blood. 2018 Jun 21;131(25):2846-2855
pubmed: 29545329
N Engl J Med. 2010 Nov 25;363(22):2091-101
pubmed: 21105791
N Engl J Med. 2013 Aug 8;369(6):529-39
pubmed: 23924003
Blood. 2015 May 14;125(20):3183-92
pubmed: 25814531
Blood. 2018 Apr 5;131(14):1522-1531
pubmed: 29358182
Blood. 2012 Jan 5;119(1):296-307
pubmed: 22010102
N Engl J Med. 2017 Nov 30;377(22):2167-2179
pubmed: 29171820
Biol Blood Marrow Transplant. 2016 Jan;22(1):4-10
pubmed: 26386318
J Clin Invest. 2018 Nov 1;128(11):4970-4979
pubmed: 30106382
Biol Blood Marrow Transplant. 2002;8(1):40-6
pubmed: 11858189
Blood. 2017 Feb 2;129(5):643-649
pubmed: 27899357
AIDS. 1999 May 7;13(7):797-804
pubmed: 10357378
Blood. 2013 Aug 22;122(8):1505-9
pubmed: 23760615
Biol Blood Marrow Transplant. 2015 Apr;21(4):761-7
pubmed: 25585275
JCI Insight. 2017 Feb 9;2(3):e89798
pubmed: 28194439
Biometrics. 1988 Sep;44(3):837-45
pubmed: 3203132
Lancet Haematol. 2015 Jan;2(1):e21-9
pubmed: 26687425