Chediak–Higashi syndrome (CHS) is a rare autosomal recessive disorder caused by biallelic LYST variants, characterized by partial albinism, recurrent infections, bleeding, and progressive neurologic decline. Majority of classic cases develop hemophagocytic lymphohistiocytosis (HLH), the main cause of early mortality. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for hematologic and immune complications, but long-term data on graft stability and late relapse are limited.
We report a 29-year-old female with CHS who experienced HLH relapse and worsening neurological symptoms nearly 18 years after haploidentical HSCT, with a history of mixed donor chimerism. Lab work showed neutropenia and hyperferritinemia, and bone marrow biopsy confirmed hemophagocytic activity. Treatment with systemic steroids and intrathecal hydrocortisone/cytarabine led to clinical improvement, with a second HSCT planned. Published series indicate favorable engraftment and survival outcomes in CHS, with no higher risk of graft failure than other genetic HLH forms. Mixed chimerism can sustain remission, suggesting full donor chimerism is not always required. However, long-term graft durability and late relapse are poorly documented.
HLH relapse can occur decades after HSCT in CHS, underscoring the need for lifelong monitoring of chimerism and immune function. Extended follow-up studies are necessary to understand late outcomes and guide management.
