Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:143

Article

Ferrua, Francesca^1,2,3,4  Galimberti, Stefania⁵  Courteille, Virginie^6,61  Slatter, Mary Anne^1,2,7  Booth, Claire⁸  Moshous, Despina^6,9,61  Neven, Benedicte^6,9,61  Blanche, Stephane^6,9,61  Cavazzana, Marina^6,10,11,12  Laberko, Alexandra¹³  Shcherbina, Anna¹³  Balashov, Dmitry¹³  Soncini, Elena¹⁴  Porta, Fulvio¹⁴  Al-Mousa, Hamoud¹⁵  Al-Saud, Bandar¹⁵  Al-Dhekri, Hasan¹⁵  Arnaout, Rand¹⁵  Formankova, Renata¹⁶  Bertrand, Yves¹⁷  Lange, Andrzej^18,19,20  Smart, Joanne²¹  Wolska-Kusnierz, Beata²²  Aquino, Victor M.²³  Dvorak, Christopher C.²⁴  Fasth, Anders^25,26  Fouyssac, Fanny^27,61  Heilmann, Carsten²⁸  Hoenig, Manfred²⁹  Schuetz, Catharina²⁹  Kelecic, Jadranka³⁰  Bredius, Robbert G. M.³¹  Lankester, Arjan C.³¹  Lindemans, Caroline A.^32,33  Suarez, Felipe^34,61  Sullivan, Kathleen E.³⁵  Albert, Michael H.³⁶  Kalwak, Krzysztof³⁷  Barlogis, Vincent^38,61  Bhatia, Monica³⁹  Bordon, Victoria⁴⁰  Czogala, Wojciech^41,66  Alonso, Laura⁴²  Dogu, Figen⁴³  Gozdzik, Jolanta⁴⁴  Ikinciogullari, Aydan^45,46  Krivan, Gergely⁴⁷  Ljungman, Per⁴⁸  Meyts, Isabelle⁴⁹  Mustillo, Peter⁵⁰  Smith, Angela R.⁵¹  Speckmann, Carsten^52,53  Sundin, Mikael^54,55  Keogh, Steven John⁵⁶  Shaw, Peter John^56,57  Boelens, Jaap Jan^32,33,58,59  Schulz, Ansgar S.²⁹  Sedlacek, Petr¹⁶  Veys, Paul⁶⁰  Mahlaoui, Nizar^6,9,61,62  Janda, Ales^63,64  Davies, E. Graham⁸  Fischer, Alain^6,9,61,65  Cowan, Morton J.²⁴  Gennery, Andrew Richard^1,2,7 

[1] Great North Childrens Hosp, Dept Pediat Immunol, Newcastle Upon Tyne, Tyne & Wear, England

[2] Great North Childrens Hosp, HSCT, Newcastle Upon Tyne, Tyne & Wear, England

[3] Ist Sci San Raffaele, Pediat Immunohematol & Bone Marrow Transplantat U, San Raffaele Telethon Inst Gene Therapy SR Tiget, Via Olgettina 60, I-20132 Milan, Italy

[4] Univ Vita Salute San Raffaele, Milan, Italy

[5] Univ Milano Bicocca, Sch Med Surg, Ctr Biostat Clin Epidemiol, Monza, Italy

[6] Paris Descartes Sorbonne Paris Cite Univ, Imagine Inst, Paris, France

[7] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England

[8] Great Ormond St Hosp Sick Children, Dept Pediat Immunol, London, England

[9] Necker Enfants Malades Hosp, AP HP, Pediat Hematol Immunol & Rheumatol Unit, Paris, France

[10] Necker Childrens Hosp, AP HP, Biotherapy Dept, Paris, France

[11] Grp Hosp Univ Ouest, AP HP, INSERM, Biotherapy Clin Invest Ctr, Paris, France

[12] Lab Human Lymphohematopoiesis, INSERM UMR 1163, Paris, France

[13] Dmitry Rogachev Fed Res Ctr Pediat Hematol Oncol, Moscow, Russia

[14] Spedali Civili Brescia, Pediat Oncol Hematol & BMT Unit, Brescia, Italy

[15] King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh, Saudi Arabia

[16] Univ Hosp Motol Prague, Dept Pediat Hematol & Oncol, Prague, Czech Republic

[17] Hosp Civils Lyon, Inst Hematol & Oncol Pediat, Lyon, France

[18] Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland

[19] Lower Silesian Ctr Cellular Transplantat, Wroclaw, Poland

[20] Natl Bone Marrow Donor Registry, Wroclaw, Poland

[21] Royal Childrens Hosp, Dept Allergy & Immunol, Melbourne, Vic, Australia

[22] Childrens Mem Hlth Inst, Immunol Dept, Warsaw, Poland

[23] Univ Texas Southwestern Med Ctr Dallas, Dept Pediat, Dallas, TX USA

[24] Univ Calif San Francisco, Div Pediat Allergy Immunol & Bone Marrow Transpla, San Francisco, CA 94143 USA

[25] Univ Gothenburg, Sahlgrenska Acad, Dept Pediat, Gothenburg, Sweden

[26] Queen Silvia Childrens Hosp, Gothenburg, Sweden

[27] Univ Hosp Nancy, Children Hosp, Pediat Oncol & Hematol Unit, Van Doeuvre Les Nancy, France

[28] Rigshosp, Pediat Clin, Copenhagen, Denmark

[29] Univ Med Ctr Ulm, Dept Pediat, Ulm, Germany

[30] Univ Hosp Ctr Zagreb, Dept Pediat, Div Allergol Clin Immunol Resp Dis & Rheumatol, Zagreb, Croatia

[31] Leiden Univ, Med Ctr, Willem Alexander Childrens Hosp, Dept Pediat, Leiden, Netherlands

[32] Univ Utrecht, Univ Med Ctr Utrecht, Dept Pediat, Utrecht, Netherlands

[33] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands

[34] Hop Necker Enfants Malad, AP HP, Hematol Adulte, Paris, France

[35] Childrens Hosp Philadelphia, Dept Pediat, Div Allergy Immunol, Philadelphia, PA 19104 USA

[36] Dr von Hauner Univ Childrens Hosp, Pediat Hematol Oncol, Munich, Germany

[37] Wroclaw Med Univ, Dept Pediat Hematol & Oncol, Wroclaw, Poland

[38] Hop Timone Enfants, Serv Dhematol Pediat, Marseille, France

[39] Columbia Univ, Coll Phys & Surg, Pediat Stem Cell Transplantat, New York, NY USA

[40] Ghent Univ Hosp, Pediat Hematol Oncol & Stem Cell Transplantat, Ghent, Belgium

[41] Univ Childrens Hosp Cracow, Krakow, Poland

[42] Hosp Univ MatemoInfantil Vall dHebron, Pediat Hematol & Oncol Dept, Barcelona, Spain

[43] Ankara Univ, Dept Pediat Immunol & Allergy, Sch Med, Ankara, Turkey

[44] Jagiellonian Univ, Univ Childrens Hosp, Transplantat Ctr, Dept Clin Immunol & Transplantol,Med Coll, Krakow, Poland

[45] Ankara Univ, Med Sch, Dept Pediat Immunol Allergy, Ankara, Turkey

[46] Ankara Univ, Med Sch, BMT Unit, Ankara, Turkey

[47] United St Istvan & St Laszlo Hosp, Dept Pediat Hematol & Stem Cell Transplantat, Budapest, Hungary

[48] Karolinska Univ Hosp, Dept Hematol, Stockholm, Sweden

[49] Katholieke Univ Leuven, Dept Immunol & Microbiol, Univ Hosp Leuven, Dept Pediat,Div Pediat Immunol, Leuven, Belgium

[50] Nationwide Childrens Hosp, Columbus, OH USA

[51] Univ Minnesota, Pediat Blood & Marrow Transplant, Minneapolis, MN USA

[52] Univ Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany

[53] Univ Freiburg, Div Pediat Hematol & Oncol, Dept Pediat & Adolescent Med, Fac Med, Freiburg, Germany

[54] Karolinska Inst, CLINTTEC, Div Pediat, Stockholm, Sweden

[55] Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Pediat Blood Disorders Immunodeficiency & SCT, Stockholm, Sweden

[56] Childrens Hosp Westmead, Canc Ctr Children, Sydney, NSW, Australia

[57] Univ Sydney, Med Program, Sydney, NSW, Australia

[58] Mem Sloan Kettering Canc Ctr, Dept Pediat, BMT & Cell Therapies Program, 1275 York Ave, New York, NY 10021 USA

[59] Univ Med Ctr, Lab Translat Immunol, Tumor Immunol, Utrecht, Netherlands

[60] Great Ormond St Hosp Sick Children, Dept BMT, London, England

[61] Necker Enfants Malades Univ Hosp, AP HP, French Natl Reference Ctr Primary Immune Deficien, Paris, France

[62] INSERM UMR 1163, Lab Human Genet Infect Dis, Necker Branch, Paris, France

[63] Univ Freiburg, Med Ctr, Ctr Pediat, Freiburg, Germany

[64] Univ Freiburg, Med Ctr, Ctr Chron Immunodeficiency, Freiburg, Germany

[65] Coll France, Paris, France

[66] Ul Lubostron 33-43, PL-30383 Krakow, Poland

关键词: CD40 ligand;    hematopoietic stem cell transplantation;    X-linked hyper-IgM syndrome;    primary immunodeficiency;   

DOI  :  10.1016/j.jaci.2018.12.1010

来源: Elsevier

【 摘 要 】

Background: CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium species infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT). Objective: We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics. Methods: We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables' relevance with respect to survival and cure. Results: Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 78.2%, 58.1%, and 72.3% 5 years after HSCT. Results were better in transplantations performed in 2000 or later and in children less than 10 years old at the time of HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT at 2 years or less from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC), and bone marrow-derived stem cells. Most rejections occurred after reduced-intensity or nonmyeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was 50% or greater donor in 85.2%. Conclusion: HSCT is curative in patients with CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS, and DFS. Prospective studies are required to compare the risks of HSCT with those of lifelong supportive therapy.

【 授权许可】

Free