Abstract
REPORT OF A FIRST CASE OF PEDIATRIC MDS WITH VEXAS SYNDROME
EJC paediatric oncology, Vol.6(Suppl 1), 100404
12/2025
DOI: 10.1016/j.ejcped.2025.100404
Abstract
Background and Aims: VEXAS syndrome is a severe autoinflammatory disorder driven by somatic UBA1 mutations, that primarily affects males over the age of 50 years. The clinical spectrum encompasses autoinflammation, bone marrow (BM) involvement with cytopenia and increased MDS/AML risk. To date, VEXAS has not been reported in children. We describe the first pediatric VEXAS patient and investigate clonal architecture during CPX-351 treatment using single cell DNA sequencing (scDNAseq).
Methods: Bulk genomic analysis (NGS and ddPCR) on total BM and CD34+ purified fractions; scDNAseq on BM from pre-/post-CPX-351 treatment. For scDNAseq, we developed a custom Missionbio Tapestri panel combined with antibody staining.
Results: A previously healthy 6-year-old boy presented with pancytopenia with splenomegaly and BM findings showing dysplasia and 7% blast excess with normal karyotype, consistent with MDS-EB. No germline predisposition was identified. Somatic UBA1 S56F and NRAS G13D mutations were identified in the BM but absent in germline testing. The presentation included intermittent skin rash and skin biopsy showing neutrophilic inflammation with leukocytoclasia, consistent with VEXAS presentation. He received two cycles of CPX-351 cytoreduction showing excellent response with reduction of abnormal blasts below quantification limits, complete resolution of the inflammatory rash and undetectable residual clones by somatic NGS.
He subsequently underwent busulfan/fludarabine/thiotepa/ATG conditioning followed by successful matched unrelated donor bone marrow transplantation (now day +135), with no relevant complications. ScDNAseq studies revealed NRAS as the ancestral clone (NRAS alone 4.7% at diagnosis) with UBA1 mutation arising second (NRAS+UBA1: 27.3%). The NRAS+UBA1-mutant clone demonstrated myeloid bias compared to NRAS-only and wildtype cells. Purified CD34+ cells showed enrichment of both UBA1 and NRAS mutations, suggesting preferential expansion within hematopoietic stem/progenitor cells.
Conclusions: We describe the first pediatric case of VEXAS MDS showing excellent response to CPX-351 followed by transplantation. We also show that the UBA1 mutation can arise secondary to Ras pathway activation.
Details
- Title: Subtitle
- REPORT OF A FIRST CASE OF PEDIATRIC MDS WITH VEXAS SYNDROME
- Creators
- Lili Kotmayer - St. Jude Children's Research HospitalMichael Halyko - University of IowaRajat Sharma - University of IowaAnjali Sharathkumar - University of IowaMarcin W. Wlodarski - St. Jude Children's Research Hospital
- Resource Type
- Abstract
- Publication Details
- EJC paediatric oncology, Vol.6(Suppl 1), 100404
- DOI
- 10.1016/j.ejcped.2025.100404
- ISSN
- 2772-610X
- eISSN
- 2772-610X
- Publisher
- Elsevier Ltd
- Language
- English
- Date published
- 12/2025
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9985024166502771
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