Cell‐Sorted EBV PCR Identifies Lineage Shift and Guides Management After Hematopoietic Cell Transplantation for Pediatric EBV‐Positive T/NK‐Cell Lymphoid Neoplasia: A Case Series

Epstein-Barr virus (EBV)-positive T/natural killer (NK)-cell lymphoid neoplasms, including chronic active EBV disease and EBV-positive T/NK-cell leukemias and lymphomas, are rare, aggressive disorders for which allogeneic hematopoietic cell transplantation (alloHCT) is the only established curative therapy. After alloHCT, plasma or whole-blood EBV polymerase chain reaction (PCR) cannot distinguish relapse from EBV-driven donor B-cell proliferation. Cell-sorted EBV PCR resolves this ambiguity by quantifying EBV DNA across lymphocyte subsets to identify the cell lineage with the highest viral burden. We report four children in whom cell-sorted EBV PCR demonstrated a post-transplant shift in predominant EBV burden from T/NK cells to B cells, enabling de-escalation from cytotoxic therapy to immunosuppression reduction and B-cell-directed treatment.