Hematopoietic stem cell transplantation is a curative therapy for transferrin receptor 1 (TFRC) deficiency.

Abstract Background Iron uptake mediated by transferrin receptor 1 (TfR1), encoded by the TFRC gene, is essential for lymphocyte development and proliferation. Autosomal recessive mutations in the human TFRC gene cause a combined immunodeficiency characterized by defective T and B cell proliferation as well as impaired class-switching. Clinical presentations have been severe in all reported cases with symptoms including recurrent sinopulmonary infections, hypogammaglobulinemia, chronic diarrhea, and intermittent cytopenias. Objective To describe outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with TFRC deficiency. Methods Retrospective chart review study of five patients with TFRC deficiency who underwent allogeneic HSCT between July 2011 and May 2018 at Boston Children's Hospital. Results Intermittent thrombocytopenia and neutropenia were a predominant feature of the clinical presentation in our cohort, and 3 patients who underwent bone marrow evaluation prior to HSCT were found to have signs of dysmyelopoiesis and dysplasia. One patient, who was transplanted at age 11 years, developed a clonal cytogenetic abnormality concerning for myelodysplastic syndrome. All 5 patients tolerated myeloablative conditioning regimens and had robust donor cell engraftment with resolution of cytopenias and independence from intravenous immunoglobulin substitution. All five patients were alive at a median follow up of 47.1 months post-transplant (range, 15.7-85.4) and none had developed acute or chronic graft-versus-host disease. Conclusions Allogeneic HSCT is curative for TFRC deficiency and rescues all known disease manifestations. Patients with TFRC deficiency may have a predisposition to malignant transformation of hematopoietic cells and may benefit from HSCT earlier in their disease course.