Hematopoietic Stem Cell Transplantation Is a Curative Therapy for Transferrin Receptor 1 (TFRC) Deficiency.
PMID 33096268 | DOI 10.1016/j.jaip.2020.10.018 · The journal of allergy and clinical immunology. In practice · 2021
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 5 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 before HSCT were found to have signs of dysmyelopoiesis and dysplasia. One patient, who had a transplant 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 5 patients were alive at a median follow-up of 47.1 months posttransplant (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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | TFRC | “Hematopoietic Stem Cell Transplantation Is a Curative Therapy for Transferrin Receptor 1 (TFRC) Deficiency.” | 0.98 | hgnc_dict_v1 |
| population | Population | “METHODS: Retrospective chart review study of 5 patients with TFRC deficiency who underwent allogeneic HSCT between July 2011 and May 2018 at Boston Children's Hospital.” | 0.80 | saudi_context_rules_v1 |