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Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study
F. Ferrua, S. Galimberti, V. Courteille, MA. Slatter, C. Booth, D. Moshous, B. Neven, S. Blanche, M. Cavazzana, A. Laberko, A. Shcherbina, D. Balashov, E. Soncini, F. Porta, H. Al-Mousa, B. Al-Saud, H. Al-Dhekri, R. Arnaout, R. Formankova, Y....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
U54 AI082973
NIAID NIH HHS - United States
R13 AI094943
NIAID NIH HHS - United States
- MeSH
- dítě MeSH
- kojenec MeSH
- kombinované imunodeficience vázané na chromozom X mortalita terapie MeSH
- lidé MeSH
- ligand CD40 nedostatek MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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.
Biotherapy Department Necker Children's Hospital AP HP Paris France
Cancer Centre for Children Children's Hospital at Westmead Sydney Australia
College de France Paris France
Department of Allergy and Immunology Royal Children's Hospital Melbourne Australia
Department of BMT Great Ormond Street Hospital for Children NHS Trust London United Kingdom
Department of Hematology Karolinska University Hospital Stockholm Sweden
Department of Pediatric Hematology and Oncology Wroclaw Medical University Wrocław Poland
Department of Pediatric Immunology and Allergy Ankara University School of Medicine Ankara Turkey
Department of Pediatric Immunology Great Ormond Street Hospital London United Kingdom
Department of Pediatrics King Faisal Specialist Hospital and Research Center Riyadh Saudi Arabia
Department of Pediatrics University Medical Center Ulm Ulm Germany
Department of Pediatrics University of Texas Southwestern Medical Center Dallas Dallas Tex
Division of Pediatrics CLINTEC Karolinska Institutet Stockholm Sweden
Hématologie Adulte Hôpital Necker AP HP Paris France
Immunology Department Children's Memorial Health Institute Warsaw Poland
INSERM UMR 1163 Laboratory of Human Genetics of Infectious Diseases Necker Branch Paris France
INSERM UMR 1163 Laboratory of Human Lymphohematopoiesis Paris France
Institut d'Hematologie et d'Oncologie Pediatrique Hospices Civils de Lyon Lyon France
Institute of Cellular Medicine Newcastle University Newcastle upon Tyne United Kingdom
Nationwide Children's Hospital Columbus Ohio
Paris Descartes Sorbonne Paris Cité University Imagine Institute Paris France
Pediatric Blood and Marrow Transplant University of Minnesota Minneapolis Minn
Pediatric Clinic Rigshospitalet Copenhagen Denmark
Pediatric Hematology Oncology and Stem Cell Transplantation Ghent University Hospital Ghent Belgium
Pediatric Hematology Oncology Dr von Hauner University Children's Hospital Munich Germany
Pediatric Oncology Hematology and BMT Unit Spedali Civili di Brescia Brescia Italy
Princess Maxima Center for Pediatric Oncology Utrecht The Netherlands
Service d'hématologie pédiatrique Hôpital de la Timone Enfants Marseille France
University Children's Hospital of Cracow Cracow Poland
Citace poskytuje Crossref.org
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- $a Ferrua, Francesca $u Department of Pediatric Immunology and HSCT, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom; San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), Pediatric Immunohematology and Bone Marrow Transplantation Unit, San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy. Electronic address: ferrua.francesca@hsr.it.
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- $a Hematopoietic stem cell transplantation for CD40 ligand deficiency: Results from an EBMT/ESID-IEWP-SCETIDE-PIDTC study / $c F. Ferrua, S. Galimberti, V. Courteille, MA. Slatter, C. Booth, D. Moshous, B. Neven, S. Blanche, M. Cavazzana, A. Laberko, A. Shcherbina, D. Balashov, E. Soncini, F. Porta, H. Al-Mousa, B. Al-Saud, H. Al-Dhekri, R. Arnaout, R. Formankova, Y. Bertrand, A. Lange, J. Smart, B. Wolska-Kusnierz, VM. Aquino, CC. Dvorak, A. Fasth, F. Fouyssac, C. Heilmann, M. Hoenig, C. Schuetz, J. Kelečić, RGM. Bredius, AC. Lankester, CA. Lindemans, F. Suarez, KE. Sullivan, MH. Albert, K. Kałwak, V. Barlogis, M. Bhatia, V. Bordon, W. Czogala, L. Alonso, F. Dogu, J. Gozdzik, A. Ikinciogullari, G. Kriván, P. Ljungman, I. Meyts, P. Mustillo, AR. Smith, C. Speckmann, M. Sundin, SJ. Keogh, PJ. Shaw, JJ. Boelens, AS. Schulz, P. Sedlacek, P. Veys, N. Mahlaoui, A. Janda, EG. Davies, A. Fischer, MJ. Cowan, AR. Gennery, SCETIDE, PIDTC, EBMT & ESID IEWP,
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- $a 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.
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- $a Galimberti, Stefania $u Center of Biostatistics for Clinical Epidemiology, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
- 700 1_
- $a Courteille, Virginie $u Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France; French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Enfants Malades University Hospital, AP-HP, Paris, France.
- 700 1_
- $a Slatter, Mary Anne $u Department of Pediatric Immunology and HSCT, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
- 700 1_
- $a Booth, Claire $u Department of Pediatric Immunology, Great Ormond Street Hospital, London, United Kingdom.
- 700 1_
- $a Moshous, Despina $u Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Enfants Malades University Hospital, AP-HP, Paris, France.
- 700 1_
- $a Neven, Benedicte $u Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Enfants Malades University Hospital, AP-HP, Paris, France.
- 700 1_
- $a Blanche, Stephane $u Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Enfants Malades University Hospital, AP-HP, Paris, France.
- 700 1_
- $a Cavazzana, Marina $u Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France; Biotherapy Department, Necker Children's Hospital, AP-HP, Paris, France; Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, AP-HP, INSERM, Paris, France; INSERM UMR 1163, Laboratory of Human Lymphohematopoiesis, Paris, France.
- 700 1_
- $a Laberko, Alexandra $u Dmitry Rogachev Federal Research Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
- 700 1_
- $a Shcherbina, Anna $u Dmitry Rogachev Federal Research Centre of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
- 700 1_
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- 700 1_
- $a Soncini, Elena $u Pediatric Oncology-Hematology and BMT Unit, Spedali Civili di Brescia, Brescia, Italy.
- 700 1_
- $a Porta, Fulvio $u Pediatric Oncology-Hematology and BMT Unit, Spedali Civili di Brescia, Brescia, Italy.
- 700 1_
- $a Al-Mousa, Hamoud $u Department of Pediatrics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
- 700 1_
- $a Al-Saud, Bandar $u Department of Pediatrics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
- 700 1_
- $a Al-Dhekri, Hasan $u Department of Pediatrics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
- 700 1_
- $a Arnaout, Rand $u Department of Pediatrics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
- 700 1_
- $a Formankova, Renata $u Department of Pediatric Hematology and Oncology, University Hospital Motol Prague, Prague, Czech Republic.
- 700 1_
- $a Bertrand, Yves $u Institut d'Hematologie et d'Oncologie Pediatrique, Hospices Civils de Lyon, Lyon, France.
- 700 1_
- $a Lange, Andrzej $u L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland; Lower Silesian Center for Cellular Transplantation & National Bone Marrow Donor Registry, Wrocław, Poland.
- 700 1_
- $a Smart, Joanne $u Department of Allergy and Immunology, Royal Children's Hospital, Melbourne, Australia.
- 700 1_
- $a Wolska-Kusnierz, Beata $u Immunology Department, Children's Memorial Health Institute, Warsaw, Poland.
- 700 1_
- $a Aquino, Victor M $u Department of Pediatrics, University of Texas Southwestern Medical Center Dallas, Dallas, Tex.
- 700 1_
- $a Dvorak, Christopher C $u Division of Pediatric Allergy, Immunology & Bone Marrow Transplantation, University of California, San Francisco, Calif.
- 700 1_
- $a Fasth, Anders $u Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg and Queen Silvia Children's Hospital, Gothenburg, Sweden.
- 700 1_
- $a Fouyssac, Fanny $u Pediatric Oncology and Hematology Unit, Children Hospital, University Hospital Nancy, Vandoeuvre-les-Nancy, France; French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Enfants Malades University Hospital, AP-HP, Paris, France.
- 700 1_
- $a Heilmann, Carsten $u Pediatric Clinic, Rigshospitalet, Copenhagen, Denmark.
- 700 1_
- $a Hoenig, Manfred $u Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
- 700 1_
- $a Schuetz, Catharina $u Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
- 700 1_
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- 700 1_
- $a Bredius, Robbert G M $u Department of Pediatrics/Willem-Alexander Children's hospital, Leiden University Medical Center, Leiden, The Netherlands.
- 700 1_
- $a Lankester, Arjan C $u Department of Pediatrics/Willem-Alexander Children's hospital, Leiden University Medical Center, Leiden, The Netherlands.
- 700 1_
- $a Lindemans, Caroline A $u Department of Pediatrics, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands; Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands.
- 700 1_
- $a Suarez, Felipe $u Hématologie Adulte, Hôpital Necker, AP-HP, Paris, France; French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Enfants Malades University Hospital, AP-HP, Paris, France.
- 700 1_
- $a Sullivan, Kathleen E $u Division of Allergy Immunology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pa.
- 700 1_
- $a Albert, Michael H $u Pediatric Hematology/Oncology, Dr. von Hauner University Children's Hospital, Munich, Germany.
- 700 1_
- $a Kałwak, Krzysztof $u Department of Pediatric Hematology and Oncology, Wroclaw Medical University, Wrocław, Poland.
- 700 1_
- $a Barlogis, Vincent $u Service d'hématologie pédiatrique, Hôpital de la Timone Enfants, Marseille, France; French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Enfants Malades University Hospital, AP-HP, Paris, France.
- 700 1_
- $a Bhatia, Monica $u Pediatric Stem Cell Transplantation, Columbia University College of Physicians and Surgeons, New York, NY.
- 700 1_
- $a Bordon, Victoria $u Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium.
- 700 1_
- $a Czogala, Wojciech $u University Children's Hospital of Cracow, Cracow, Poland.
- 700 1_
- $a Alonso, Laura $u Pediatric Hematology and Oncology Department, Hospital Universitario MaternoInfantil Vall d'Hebron, Barcelona, Spain.
- 700 1_
- $a Dogu, Figen $u Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey.
- 700 1_
- $a Gozdzik, Jolanta $u Department of Clinical Immunology and Transplantology, Jagiellonian University, Medical Collage, Transplantation Center, University Children's Hospital, Cracow, Poland.
- 700 1_
- $a Ikinciogullari, Aydan $u Department of Pediatric Immunology-Allergy and BMT Unit, Ankara University Medical School, Ankara, Turkey.
- 700 1_
- $a Kriván, Gergely $u Department of Pediatric Hematology and Stem Cell Transplantation United St. István and St László Hospital, Budapest, Hungary.
- 700 1_
- $a Ljungman, Per $u Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
- 700 1_
- $a Meyts, Isabelle $u Department of Pediatrics, University Hospitals Leuven, Division of Pediatric Immunology, Department of Immunology and Microbiology, Catholic University Leuven, Leuven, Belgium.
- 700 1_
- $a Mustillo, Peter $u Nationwide Children's Hospital, Columbus, Ohio.
- 700 1_
- $a Smith, Angela R $u Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minn.
- 700 1_
- $a Speckmann, Carsten $u Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
- 700 1_
- $a Sundin, Mikael $u Division of Pediatrics, CLINTEC, Karolinska Institutet, Stockholm, Sweden; Pediatric Blood Disorders, Immunodeficiency and SCT, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
- 700 1_
- $a Keogh, Steven John $u Cancer Centre for Children, Children's Hospital at Westmead, Sydney, Australia.
- 700 1_
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- 700 1_
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- 700 1_
- $a Schulz, Ansgar S $u Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
- $a Janda, Ales $u Center for Pediatrics and Center for Chronic Immunodeficiency, Medical Center, University of Freiburg, Freiburg, Germany.
- 700 1_
- $a Davies, E Graham $u Department of Pediatric Immunology, Great Ormond Street Hospital, London, United Kingdom.
- 700 1_
- $a Fischer, Alain $u Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France; Pediatric Hematology-Immunology and Rheumatology Unit, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; French National Reference Center for Primary Immune Deficiencies (CEREDIH), Necker Enfants Malades University Hospital, AP-HP, Paris, France; College de France, Paris, France.
- 700 1_
- $a Cowan, Morton J $u Division of Pediatric Allergy, Immunology & Bone Marrow Transplantation, University of California, San Francisco, Calif.
- 700 1_
- $a Gennery, Andrew Richard $u Department of Pediatric Immunology and HSCT, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
- 710 2_
- $a SCETIDE, PIDTC, EBMT & ESID IEWP
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