Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations.
Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations.
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DOI：
10.1016/j.jaci.2017.03.049
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation and the Primary Immune Deficiency Treatment Consortium
中科院分区：
文献类型：
--
作者：
Leiding JW;Okada S;Hagin D;Abinun M;Shcherbina A;Balashov DN;Kim VHD;Ovadia A;Guthery SL;Pulsipher M;Lilic D;Devlin LA;Christie S;Depner M;Fuchs S;van Royen-Kerkhof A;Lindemans C;Petrovic A;Sullivan KE;Bunin N;Kilic SS;Arpaci F;Calle-Martin O;Martinez-Martinez L;Aldave JC;Kobayashi M;Ohkawa T;Imai K;Iguchi A;Roifman CM;Gennery AR;Slatter M;Ochs HD;Morio T;Torgerson TR;Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation and the Primary Immune Deficiency Treatment Consortium
信号转导子和转录激活子 1 (STAT1) 的功能获得 (GOF) 突变会导致对一系列感染、自身免疫、免疫失调和联合免疫缺陷的易感性。疾病表现可以是轻微的，也可以是严重的，甚至危及生命。造血干细胞移植（HSCT）已被用于一些症状更严重的患者来治疗和治愈这种疾病。然而，造血干细胞移植治疗这种疾病的结果尚未明确。我们试图汇总全球 GOF-STAT1 突变患者 HSCT 的经验，并评估结果，包括供体植入、总生存率、移植物抗宿主病和移植相关并发症。数据收集自 15 名 GOF-STAT1 突变患者的国际队列，这些患者使用各种预处理方案和供体来源接受了 HSCT。回顾性数据收集可以评估移植的结果。进行体外功能测试以确认每个已识别的 STAT1 变体实际上是 GOF 突变。在这个由 15 名 GOF-STAT1 突变患者组成的队列中，主要供体植入率为 74%，总生存率仅为 40%。继发性移植失败很常见（50%），移植后无事件生存率很差（100 天时为 10%）。一部分患者在移植前患有噬血细胞淋巴组织细胞增多症，导致其预后不佳。我们的数据表明，对于 GOF-STAT1 突变患者进行 HSCT 是有效的，但存在继发性移植失败和死亡的显着风险。
Gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) cause susceptibility to a range of infections, autoimmunity, immune dysregulation, and combined immunodeficiency. Disease manifestations can be mild or severe and life-threatening. Hematopoietic stem cell transplantation (HSCT) has been used in some patients with more severe symptoms to treat and cure the disorder. However, the outcome of HSCT for this disorder is not well established. We sought to aggregate the worldwide experience of HSCT in patients with GOF-STAT1 mutations and to assess outcomes, including donor engraftment, overall survival, graft-versus-host disease, and transplant-related complications. Data were collected from an international cohort of 15 patients with GOF-STAT1 mutations who had undergone HSCT using a variety of conditioning regimens and donor sources. Retrospective data collection allowed the outcome of transplantation to be assessed. In vitro functional testing was performed to confirm that each of the identified STAT1 variants was in fact a GOF mutation. Primary donor engraftment in this cohort of 15 patients with GOF-STAT1 mutations was 74%, and overall survival was only 40%. Secondary graft failure was common (50%), and posttransplantation event-free survival was poor (10% by 100 days). A subset of patients had hemophagocytic lymphohistiocytosis before transplant, contributing to their poor outcomes. Our data indicate that HSCT for patients with GOF-STAT1 mutations is curative but has significant risk of secondary graft failure and death.
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影响因子：
46.9
作者：
Hu, Hao;Roach, Jared C.;Coon, Hilary;Guthery, Stephen L.;Voelkerding, Karl V.;Margraf, Rebecca L.;Durtschi, Jacob D.;Tavtigian, Sean V.;Shankaracharya;Wu, Wilfred;Scheet, Paul;Wang, Shuoguo;Xing, Jinchuan;Glusman, Gustavo;Hubley, Robert;Li, Hong;Garg, Vidu;Moore, Barry;Hood, Leroy;Galas, David J.;Srivastava, Deepak;Reese, Martin G.;Jorde, Lynn B.;Yandell, Mark;Huff, Chad D.
通讯作者：
Huff, Chad D.
影响因子：
6.2
作者：
DEEG, HJ;LUM, LG;STORB, R
通讯作者：
STORB, R
影响因子：
7
作者：
Boisson-Dupuis S;Kong XF;Okada S;Cypowyj S;Puel A;Abel L;Casanova JL
通讯作者：
Casanova JL
DOI：
10.1084/jem.20110958
发表时间：
2011-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Liu L;Okada S;Kong XF;Kreins AY;Cypowyj S;Abhyankar A;Toubiana J;Itan Y;Audry M;Nitschke P;Masson C;Toth B;Flatot J;Migaud M;Chrabieh M;Kochetkov T;Bolze A;Borghesi A;Toulon A;Hiller J;Eyerich S;Eyerich K;Gulácsy V;Chernyshova L;Chernyshov V;Bondarenko A;Grimaldo RM;Blancas-Galicia L;Beas IM;Roesler J;Magdorf K;Engelhard D;Thumerelle C;Burgel PR;Hoernes M;Drexel B;Seger R;Kusuma T;Jansson AF;Sawalle-Belohradsky J;Belohradsky B;Jouanguy E;Bustamante J;Bué M;Karin N;Wildbaum G;Bodemer C;Lortholary O;Fischer A;Blanche S;Al-Muhsen S;Reichenbach J;Kobayashi M;Rosales FE;Lozano CT;Kilic SS;Oleastro M;Etzioni A;Traidl-Hoffmann C;Renner ED;Abel L;Picard C;Maródi L;Boisson-Dupuis S;Puel A;Casanova JL
通讯作者：
Casanova JL
影响因子：
14.2
作者：
Sampaio, Elizabeth P.;Hsu, Amy P.;Pechacek, Joseph;Bax, Hannelore I.;Dias, Dalton L.;Paulson, Michelle L.;Chandrasekaran, Prabha;Rosen, Lindsey B.;Carvalho, Daniel S.;Ding, Li;Vinh, Donald C.;Browne, Sarah K.;Datta, Shrimati;Milner, Joshua D.;Kuhns, Douglas B.;Priel, Debra A. Long;Sadat, Mohammed A.;Shiloh, Michael;De Marco, Brendan;Alvares, Michael;Gillman, Jason W.;Ramarathnam, Vivek;de la Morena, Maite;Bezrodnik, Liliana;Moreira, Ileana;Uzel, Gulbu;Johnson, Daniel;Spalding, Christine;Zerbe, Christa S.;Wiley, Henry;Greenberg, David E.;Hoover, Susan E.;Rosenzweig, Sergio D.;Galgiani, John N.;Holland, Steven M.
通讯作者：
Holland, Steven M.