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

被引:17
作者
Naviglio, Samuele [1 ,2 ]
Soncini, Elena [3 ]
Vairo, Donatella [4 ,5 ]
Lanfranchi, Arnalda [6 ]
Badolato, Raffaele [4 ,7 ,8 ]
Porta, Fulvio [3 ]
机构
[1] Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy
[2] Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Trieste, Italy
[3] Asst Spedali Civili, UO Oncoematol Pediat & Trapianto Midollo Osseo, Brescia, Italy
[4] Ist Med Mol Angelo Nocivelli, Brescia, Italy
[5] Univ Brescia, Dept Mol & Translat Med, Brescia, Italy
[6] Asst Spedali Civili, Sez Ematol Lab, UO Lab Anal Chim Clin, Cellule Staminali, Brescia, Italy
[7] Univ Brescia, Dept Expt & Clin Sci, Brescia, Italy
[8] Asst Spedali Civili, Clin Pediat, Ple Spedali Civili 1, I-25123 Brescia, Italy
关键词
Hematopoietic stem cell transplantation; STAT1; deficiency; Primary immunodeficiency; Signaling; MYCOBACTERIAL DISEASE; INBORN-ERRORS; MUTATIONS; RESPONSES; IMPAIRMENT; IMMUNITY; GATA2; FORM;
D O I
10.1007/s10875-017-0430-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-alpha. 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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收藏
页码:701 / 706
页数:6
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