PMC8794793_01
Family Pedigree.
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She had two living non-hearing impaired healthy siblings ( Figure 1 ).
PMC8794793_02
Adenoviremia cleared with Unmanipulated MSD HCT. Adenovirus viral load followed over time as compared with ALT and absolute CD3+T cell quantity. ALT is an indicator of liver inflammation and CD3+T cell quantity changes after MSD. Post MSD HCT, adenoviral load rapidly increases, as does ALT, likely secondary to rapid viral lysis from donor-derived CD3+ T cells. ADV, adenovirus; ALT, alanine aminotransferase; CTL, cytotoxic T lymphocyte infusion; GvHD, graft versus host disease HCT, hematopoietic cell transplant; MSD, matched sibling donor.
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Partial clinical improvement with reduction in liver function tests, improvement of liver synthetic dysfunction, and reduced adenovirus viral load were achieved but not sustained ( Figure 2 ). The degree of viremia ( Figure 2 ) progressively declined and was <1,000 copies/mL within seven weeks post-HCT with associated improvement in transaminases.
Histopathology of liver graft-versus-host disease. (A) H&E stain showing predominantly portal lymphoplasmacytic infiltration disrupting the interface (square) expanding two adjacent portal zones; arrow to interlobular bile duct. (B) CD3 Immunochemistry showing T cell lymphocytic infiltrates in the epithelium of the bile duct, lymphocytic infiltrates predominantly in the portal tracts with associated interlobular bile duct injury.
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Unfortunately, despite a decline in adenoviremia, she developed direct hyperbilirubinemia with biopsy confirmed acute stage 3 liver GvHD ( Figure 3 ) without signs of skin or intestinal GvHD.
Donor percent chimerism as measured by STR was followed over time. Full donor-derived T cell chimerism was maintained. HCT, hematopoietic cell transplant; STR, single tandem repeat.
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She has shown consistently appropriate T cell engraftment with > 90% donor-derived T cells ( Figure 4 ).