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.