Successful Second CBT for Graft Failure After First CBT for Adult-Onset Familial Hemophagocytic Lymphohistiocytosis Type 3: A Case Report

•We report a rare case of adult onset FHL that presented with recurrent HLH, followed by neurological symptoms.•Diagnosis was successfully made by rare variants of UNC13D (c.2367+1 g>a and c.2588 g>a), which were compound heterozygous pathogenic mutations.•The patient experienced graft rejection of the first CBT but was successfully salvaged by the second.•CBT might be a promising alternative donor source with the advantages of rapidity and avoidance of related donors with a high risk of harboring the same genetic mutation. Familial hemophagocytic lymphohistiocytosis (FHL) is a rare inherited autosomal recessive immune deficiency that usually manifests during infancy or early childhood, rarely occurring in adults. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for FHL. However, optimal conditioning regimens for adult-onset FHL have not yet been established. Herein, we report a case of adult-onset FHL. A 37-year-old man presented with fever, liver dysfunction, and pancytopenia, which improved temporarily with corticosteroid therapy. However, he later developed encephalitis and myelitis. Genetic analysis revealed rare variants of UNC13D (c.2367+1 g>a and c.2588 g>a), which were compound heterozygous pathogenic mutations. FHL type 3 was diagnosed, and treatment based on the hemophagocytic lymphohistiocytosis (HLH) 1994 protocol was initiated. The patient underwent cord blood transplantation (CBT) with myeloablative conditioning using fludarabine, melphalan, and total-body irradiation (TBI), which resulted in graft rejection. The patient was successfully rescued by a second CBT following reduced-intensity conditioning with fludarabine, cyclophosphamide, and TBI. Although graft failure is an important complication especially in CBT, it could be managed by appropriate treatment, and that cord blood would be a promising alternative source with the advantages of rapidity and avoidance of related donors with a high risk of harboring the same genetic mutation.