Abstract
Purpose
Complete signal transducer and activator of transcription 1 (STAT1) deficiency is a rare autosomal recessive condition characterized by impairment of intracellular signaling from both type I and type II interferons (IFN). Affected patients are prone to early severe mycobacterial and viral infections, which usually result in death before 18 months of age. We previously reported a patient affected by complete STAT1 deficiency who underwent hematopoietic stem cell transplantation (HSCT). Here, we describe the transplantation procedures and long-term outcomes.
Methods
The patient, who had suffered multiple life-threatening mycobacterial and viral infections in the first years of life, underwent HSCT at 4 years of age from a partially matched (HLA compatibility 8/10) unrelated donor after a myeloablative conditioning regimen consisting of busulfan, cyclophosphamide, and anti-thymocyte globulin.
Results
Hematological reconstitution was detected at d+15, with full donor engraftment demonstrated by molecular analysis of leukocytes. Several complications occurred in the post-transplantation phase, including acute graft versus host disease, posterior reversible encephalopathy, thrombotic thrombocytopenic purpura, bilateral keratoconjunctivitis with complete loss of vision, and chronic lower limb lymphedema. Analysis of STAT1 in CD3+ cells at 90 and 120 days after HSCT by flow cytometry showed normal STAT1 phosphorylation levels in response to IFN-α.
Conclusions
Notably, no severe infections occurred after discharge (day + 90) during a 9-year follow-up, suggesting that normal response to IFNs in hematopoietic cells is sufficient to provide protection in humans.
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Samuele Naviglio reviewed the study and wrote the manuscript. Elena Soncini designed the study and revised the manuscript. Donatella Vairo performed functional studies and revised the manuscript. Arnalda Lanfranchi performed studies for functional reconstitution and revised the manuscript. Raffaele Badolato supervised the project and helped to write the manuscript. Fulvio Porta made substantial contributions to the interpretation of data and revised the manuscript.
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Raffaele Badolato and Fulvio Porta share senior authorship
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Naviglio, S., Soncini, E., Vairo, D. et al. Long-Term Survival After Hematopoietic Stem Cell Transplantation for Complete STAT1 Deficiency. J Clin Immunol 37, 701–706 (2017). https://doi.org/10.1007/s10875-017-0430-6
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DOI: https://doi.org/10.1007/s10875-017-0430-6