Familial hemophagocytic lymphohistiocytosis type 2 (FHL2) is a rare congenital disorder caused by PRF1 mutations that leads to life-threatening hemophagocytic lymphohistiocytosis during infancy. Hematopoietic cell transplantation (HCT) is the only curative treatment, but optimal transplantation strategies remain unclear. We report two cases of infants with FHL2 successfully treated with cord blood transplantation (CBT) following reduced-intensity conditioning (RIC). Case 1: A 1 month-old boy presented with fever, pancytopenia, and multi-organ failure. Genetic testing identified compound heterozygous PRF1 mutations. After immunochemotherapy, he underwent RIC-CBT at 2 months of age. Engraftment occurred on day 16, complicated by grade II acute graft-versus-host disease (GVHD) and sinusoidal obstruction syndrome, both successfully managed. He remains alive and disease-free 10 years post-transplant with complete donor chimerism. Case 2: A 1 month-old girl presented with fever, respiratory failure, and pancytopenia. She was diagnosed with FHL2 due to a homozygous PRF1 mutation. Following immunochemotherapy, she underwent RIC-CBT at 3 months of age. Engraftment occurred on day 15, without GVHD. She developed remains alive and disease-free 2.5 years later, with stable donor-dominant mixed chimerism (approximately 90%). These cases highlight the feasibility and efficacy of immunochemotherapy followed by RIC-CBT in infants with FHL2.
Keywords: Cord blood transplantation; Familial hemophagocytic lymphohistiocytosis; PRF1 mutation; Reduced-intensity conditioning.
© 2026. The Author(s), under exclusive licence to Japanese Society of Hematology.