Hematopoietic Stem Cell Transplant in Nuclear Factor KB Essential Modulator Deficiency: A Case Report

Abstract

IntroductionInborn errors of immunity (IEI) are genetic defects characterized by recurrent infections, autoimmunity, and malignancy and often have hematopoietic functions. Therefore, replacement of poorly functioning stem cells by healthy donor hematopoietic stem cell transplantation (HSCT) represents a reasonable therapeutic approach. Herein, we describe the initial management and outcome of a patient with nuclear factor KB (NF-kB) essential modulator (NEMO) deficiency, a rare IEI, who was referred for HSCT. Case DescriptionA 12-month-old male with genetically confirmed NEMO deficiency syndrome was referred for curative correction via HSCT for underlying IEI. Prior to transplantation, he had oral thrush, multiple episodes of gram-negative bacteremia, complicated by septic emboli to the brain and lungs, persistent norovirus gastroenteritis, SARS-CoV-2 respiratory tract infection, and adenoviremia. Multiple GI biopsies were inconclusive for colitis. At the time of HSCT, the only persistent symptom was loose stools secondary to norovirus. There were no well-matched unrelated or sibling donors, so his unaffected father who was a 6/10 match was selected. He underwent a reduced toxicity preparative with fludar-abine/busulfan/rabbit Anti-thymocyte globulin. 12 days following HSCT, prior to engraftment, the patient developed fevers and hypotension and required transfer to the PICU. Unfortunately, the patient died 2 days later secondary to Stenotrophomonas bacteremia. Discussion/ConclusionHSCT is the only curative treatment option for patients with IEI. NEMO deficiency syndrome displays variability in clinical and immunological phenotype, and not all patients require curative treatment. In current literature, HSCT has been performed in 29 patients with NEMO deficiency syndrome. The global survival rate at 5 years is 74% with severe infection being the leading cause of death. Following HSCT, most surviving patients achieve reconstitution of the immune system including immunoglobulin levels though response to vaccinations is often poor. HSCT does not improve non-hematopoietic abnormalities, particularly colitis. Case reports indicate that colitis can persist or worsen following HSCT. Despite the challenges that persist with HSCT for NEMO deficiency syndrome, curative therapy should remain a consideration for profound immune deficiency, and additional studies are needed to improve post-HSCT survival and management of non-hematopoietic complications.