Diagnosis and treatment of familial hemophagocytic lymphohistiocytosis with isolated central nervous system involvement: A case report

Familial hemophagocytic lymphohistiocytosis (FHL) is the prototypical genetic form of hemophagocytic lymphohistiocytosis (HLH), a potentially fatal hyperinflammatory condition. Limited awareness of HLH with isolated central nervous system (CNS) involvement often leads to underdiagnosis or diagnostic delay. Here, we report a 13-year-old girl with FHL type 3 (FHL3) presenting with isolated CNS involvement who subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT). This case expands the clinical spectrum of FHL3 and highlights that isolated neurological symptoms may be the initial or sole manifestation of FHL, even without systemic signs. Allogeneic HSCT remains the only definitive therapy for FHL. The patient received a conditioning regimen comprising thiotepa, etoposide, busulfan, cyclophosphamide, and antithymocyte globulin (TT/VP16/BU/CY/ATG). The graft consisted of 20.4 × 10⁸/kg mononuclear cells and 4.71 × 10⁶/kg CD34 + cells. Graft-versus-host disease (GVHD) prophylaxis included cyclosporine A (CsA), mycophenolate mofetil (MMF), and methotrexate (MTX). Neutrophil engraftment (absolute neutrophil count ≥ 0.5 × 10⁹/L) occurred on day + 13, and platelet engraftment (≥ 20 × 10⁹/L) on day + 19. The patient did not develop GVHD and achieved full, stable donor chimerism with successful engraftment and minimal toxicity. Neurological remission was observed following transplantation. At the last follow-up on day 679, the patient remained alive without neurological relapse or systemic HLH. In conclusion, this patient achieved long-term CNS remission and correction of the underlying molecular defect following allogeneic HSCT with a TT/VP16/BU/CY/ATG conditioning regimen.