Suspected late graft failure and graft versus host disease 34 years after hematopoietic stem cell transplantation clinically and pathologically presenting as host versus graft disease with liver injury

Abstract

A 36-year-old man who underwent hematopoietic stem cell transplantation (HSCT) at the age of 2 years for severe combined immunodeficiency, presented with jaundice, skin rash, and elevated liver function tests 34 years after HSCT. Liver biopsy showed bile duct injury and cholestasis. Viral studies, autoimmune panel, review of medications, and imaging did not establish a cause of liver injury. However, graft-versus-host disease (GVHD) was unlikely because of the remote history of HSCT. Short tandem repeat-polymerase chain reaction (STR-PCR) chimerism analysis showed that the percentage of donor DNA in the liver biopsy specimen was very low (11 %); hence, host-versus-graft disease (HVGD) was implicated. Because STR analysis of patient’s blood showed a mixed chimera with 11 % donor DNA, graft failure was suspected; however, fractionated STR analysis ruled out complete graft failure. Overall, this case outlines liver injury caused by HVGD in the absence of complete graft failure 34 years after HSCT, which has never been reported in the literature. STR-PCR analysis was essential for mitigating the diagnostic dilemma.