Graft-versus-host disease after liver transplantation is associated with bone marrow failure, hemophagocytosis, and DNMT3A mutations
| Autor: | Luke B Fletcher, Thomas G. DeLoughery, Susan L. Orloff, Grover C. Bagby, Ken Gatter, Rachel J. Cook, Jessica Leonard, Erin Maynard, Jennifer Dunlap, Richard D. Press, Kelli M. Leong, Laura F. Newell, Ali J. Olyaei, Richard T. Maziarz, C. Kristian Enestvedt, Joseph S. Bubalo |
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| Rok vydání: | 2021 |
| Předmět: |
Myeloid
medicine.medical_treatment Graft vs Host Disease Liver transplantation Lymphohistiocytosis Hemophagocytic immune system diseases medicine Immunology and Allergy Humans Pharmacology (medical) Bone Marrow Transplantation Transplantation Hemophagocytic lymphohistiocytosis business.industry Bone marrow failure Bone Marrow Failure Disorders medicine.disease Liver Transplantation Haematopoiesis surgical procedures operative medicine.anatomical_structure Graft-versus-host disease Immunology Mutation Bone marrow Hemophagocytosis business |
| Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant SurgeonsREFERENCES. 21(12) |
| ISSN: | 1600-6143 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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