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Long-Term Survival After Hematopoietic Stem Cell Transplantation for Complete STAT1 Deficiency

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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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Authors and Affiliations

  1. Department of Medicine, Surgery, and Health Sciences, University of Trieste, Trieste, Italy

    Samuele Naviglio

  2. Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy

    Samuele Naviglio

  3. U.O. Oncoematologia pediatrica e Trapianto di Midollo osseo, Asst Spedali Civili, Brescia, Italy

    Elena Soncini & Fulvio Porta

  4. Istituto di Medicina Molecolare “Angelo Nocivelli”, Brescia, Italy

    Donatella Vairo & Raffaele Badolato

  5. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

    Donatella Vairo

  6. U.O. Laboratorio di Analisi chimico cliniche, Sezione di Ematologia Lab, Cellule staminali, Asst Spedali Civili, Brescia, Italy

    Arnalda Lanfranchi

  7. Department of Experimental and Clinical Sciences, University of Brescia, Brescia, Italy

    Raffaele Badolato

  8. Clinica pediatrica, Asst Spedali Civili, P.le Spedali civili 1, 25123, Brescia, Italy

    Raffaele Badolato

Authors
  1. Samuele Naviglio
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  2. Elena Soncini
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  3. Donatella Vairo
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  4. Arnalda Lanfranchi
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  5. Raffaele Badolato
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  6. Fulvio Porta
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Contributions

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.

Corresponding author

Correspondence to Raffaele Badolato.

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Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

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

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