Graft-versus-host disease after liver transplantation is associated with bone marrow failure, hemophagocytosis, and DNMT3A mutations.
clinical research/practice
graft-versus-host disease (GVHD)
hematology/oncology
immune regulation
immunosuppression/immune modulation
liver transplantation/hepatology
molecular biology: DNA
monitoring: immune
translational research/science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
16
04
2021
received:
23
02
2021
accepted:
30
04
2021
pubmed:
8
5
2021
medline:
1
2
2022
entrez:
7
5
2021
Statut:
ppublish
Résumé
Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.
Identifiants
pubmed: 33961341
doi: 10.1111/ajt.16635
pii: S1600-6135(22)08837-2
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
3894-3906Subventions
Organisme : National Institute of Child Health and Human Development
ID : 1K23 HD091369-01
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.
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