-
Je něco špatně v tomto záznamu ?
JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study
M. Fischer, P. Olbrich, J. Hadjadj, V. Aumann, S. Bakhtiar, V. Barlogis, P. von Bismarck, M. Bloomfield, C. Booth, EP. Buddingh, D. Cagdas, M. Castelle, AY. Chan, S. Chandrakasan, K. Chetty, P. Cougoul, E. Crickx, J. Dara, A. Deyà-Martínez, S....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu multicentrická studie, časopisecké články, práce podpořená grantem
- MeSH
- dítě MeSH
- inhibitory Janus kinas * terapeutické užití MeSH
- lidé MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- syndromy imunologické nedostatečnosti * terapie MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
BACKGROUND: Inborn errors of immunity (IEI) with dysregulated JAK/STAT signaling present with variable manifestations of immune dysregulation and infections. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but initially reported outcomes were poor. JAK inhibitors (JAKi) offer a targeted treatment option that may be an alternative or bridge to HSCT. However, data on their current use, treatment efficacy and adverse events are limited. OBJECTIVE: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers. METHODS: We conducted a multicenter retrospective study on patients with a genetic disorder of hyperactive JAK/STAT signaling who received JAKi treatment for at least 3 months. RESULTS: Sixty-nine patients (72% children) were evaluated (45 STAT1 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 1 JAK1-GOF). Ruxolitinib was the predominantly prescribed JAKi (80%). Overall, treatment resulted in improvement (partial or complete remission) of clinical symptoms in 87% of STAT1-GOF and in 90% of STAT3-GOF patients. We documented highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 91% overall survival. CONCLUSIONS: Our study suggests that JAKi may be highly effective to treat symptomatic JAK/STAT IEI patients. Prospective studies to define optimal JAKi dosing for the variable clinical presentations and age ranges should be pursued.
Allergy and Clinical Immunology Unit Tel Aviv Sourasky Medical Center Tel Aviv Israel
Children's Health Ireland Crumlin Dublin Ireland
Clinic for General Pediatrics University Hospital Schleswig Holstein Kiel Germany
Departamento de Pediatría Facultad de Medicina Universidad de Sevilla Seville Spain
Department of Immunology University Hospital Zurich University of Zurich Zurich Switzerland
Department of Pediatric Immunology Hacettepe University Medical School Ankara Turkey
Department of Pediatrics CHU Ste Justine Université de Montréal Montreal Canada
Department of Pediatrics Hospital Universitari Son Espases Palma Spain
Department of Pediatrics Tallinn Children's Hospital Tallinn Estonia
Institute of Biomedicine and Translational Medicine University of Tartu Tartu Estonia
Institute of Immunity and Transplantation University College London London England United Kingdom
Istanbul University Cerrahpasa Pediatric Immunology and Allergy Istanbul Turkey
Oncopole Institut Universitaire du cancer de toulouse Toulouse France
Pediatric Hematology Unit Centre Hospitalier Universitaire Regional de Lille Lille France
Pediatric Hematology Unit Latimone University Hospital Marseille France
Rheumatology Department Hospital Universitari i Politècnic La Fe Valencia Spain
Sorbonne University Department of Internal Medicine APHP Saint Antoine Hospital F 75012 Paris France
Universitat de Barcelona Institut de Recerca Sant Joan de Déu Barcelona Spain
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc24007807
- 003
- CZ-PrNML
- 005
- 20240423160303.0
- 007
- ta
- 008
- 240412s2024 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.jaci.2023.10.018 $2 doi
- 035 __
- $a (PubMed)37935260
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Fischer, Marco $u Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland; Department of Immunology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- 245 10
- $a JAK inhibitor treatment for inborn errors of JAK/STAT signaling: An ESID/EBMT-IEWP retrospective study / $c M. Fischer, P. Olbrich, J. Hadjadj, V. Aumann, S. Bakhtiar, V. Barlogis, P. von Bismarck, M. Bloomfield, C. Booth, EP. Buddingh, D. Cagdas, M. Castelle, AY. Chan, S. Chandrakasan, K. Chetty, P. Cougoul, E. Crickx, J. Dara, A. Deyà-Martínez, S. Farmand, R. Formankova, AR. Gennery, LI. Gonzalez-Granado, D. Hagin, LG. Hanitsch, J. Hanzlikovà, F. Hauck, J. Ivorra-Cortés, K. Kisand, A. Kiykim, J. Körholz, TR. Leahy, J. van Montfrans, Z. Nademi, B. Nelken, S. Parikh, S. Plado, J. Ramakers, A. Redlich, F. Rieux-Laucat, JG. Rivière, Y. Rodina, PR. Júnior, S. Salou, C. Schuetz, A. Shcherbina, MA. Slatter, F. Touzot, E. Unal, AC. Lankester, S. Burns, MRJ. Seppänen, O. Neth, MH. Albert, S. Ehl, B. Neven, C. Speckmann
- 520 9_
- $a BACKGROUND: Inborn errors of immunity (IEI) with dysregulated JAK/STAT signaling present with variable manifestations of immune dysregulation and infections. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but initially reported outcomes were poor. JAK inhibitors (JAKi) offer a targeted treatment option that may be an alternative or bridge to HSCT. However, data on their current use, treatment efficacy and adverse events are limited. OBJECTIVE: We evaluated the current off-label JAKi treatment experience for JAK/STAT inborn errors of immunity (IEI) among European Society for Immunodeficiencies (ESID)/European Society for Blood and Marrow Transplantation (EBMT) Inborn Errors Working Party (IEWP) centers. METHODS: We conducted a multicenter retrospective study on patients with a genetic disorder of hyperactive JAK/STAT signaling who received JAKi treatment for at least 3 months. RESULTS: Sixty-nine patients (72% children) were evaluated (45 STAT1 gain of function [GOF], 21 STAT3-GOF, 1 STAT5B-GOF, 1 suppressor of cytokine signaling 1 [aka SOCS1] loss of function, 1 JAK1-GOF). Ruxolitinib was the predominantly prescribed JAKi (80%). Overall, treatment resulted in improvement (partial or complete remission) of clinical symptoms in 87% of STAT1-GOF and in 90% of STAT3-GOF patients. We documented highly heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. Adverse events including infection and weight gain were frequent (38% of patients) but were mild (grade I-II) and transient in most patients. At last follow-up, 52 (74%) of 69 patients were still receiving JAKi treatment, and 11 patients eventually underwent HSCT after receipt of previous JAKi bridging therapy, with 91% overall survival. CONCLUSIONS: Our study suggests that JAKi may be highly effective to treat symptomatic JAK/STAT IEI patients. Prospective studies to define optimal JAKi dosing for the variable clinical presentations and age ranges should be pursued.
- 650 _2
- $a dítě $7 D002648
- 650 _2
- $a lidé $7 D006801
- 650 12
- $a inhibitory Janus kinas $x terapeutické užití $7 D000075242
- 650 _2
- $a retrospektivní studie $7 D012189
- 650 _2
- $a prospektivní studie $7 D011446
- 650 12
- $a syndromy imunologické nedostatečnosti $x terapie $7 D007153
- 650 _2
- $a výsledek terapie $7 D016896
- 655 _2
- $a multicentrická studie $7 D016448
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Olbrich, Peter $u Pediatric Infectious Diseases, Rheumatology and Immunology Unit, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS/ Universidad de Sevilla/CSIC, Red de Investigación Traslacional en Infectología Pediátrica RITIP, Seville, Spain; Departamento de Pediatría, Facultad de Medicina, Universidad de Sevilla, Seville, Spain
- 700 1_
- $a Hadjadj, Jérôme $u Sorbonne University, Department of Internal Medicine, APHP, Saint-Antoine Hospital, F-75012 Paris, France
- 700 1_
- $a Aumann, Volker $u Pediatric Oncology Department, Otto von Guericke University Children's Hospital Magdeburg, Magdeburg, Germany
- 700 1_
- $a Bakhtiar, Shahrzad $u Division for Stem Cell Transplantation, Immunology and Intensive Care Medicine, Department for Children and Adolescents Medicine, University Hospital Frankfurt, Frankfurt am Main, Germany
- 700 1_
- $a Barlogis, Vincent $u Pediatric Hematology Unit, Latimone University Hospital, Marseille, France
- 700 1_
- $a von Bismarck, Philipp $u Clinic for General Pediatrics, University Hospital Schleswig-Holstein, Kiel, Germany
- 700 1_
- $a Bloomfield, Markéta $u Department of Immunology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic
- 700 1_
- $a Booth, Claire $u Department of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital London, London, England, United Kingdom
- 700 1_
- $a Buddingh, Emmeline P $u Willem-Alexander Children's Hospital, Department of Pediatrics, Pediatric Stem cell Transplantation program, Leiden University Medical Center, Leiden, The Netherlands
- 700 1_
- $a Cagdas, Deniz $u Department of Pediatric Immunology, Hacettepe University Medical School, Ankara, Turkey
- 700 1_
- $a Castelle, Martin $u Immuno-hematology and Rheumatology Unit, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, INSERM 1163, Institut Imagine, Paris, Île-de-France, France
- 700 1_
- $a Chan, Alice Y $u Division of Allergy, Immunology, Bone Marrow Transplantation, Department of Pediatrics, University of California, San Francisco, Calif
- 700 1_
- $a Chandrakasan, Shanmuganathan $u Aflac Cancer and Blood Disorder Center, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Ga
- 700 1_
- $a Chetty, Kritika $u Department of Paediatric Immunology and Gene Therapy, Great Ormond Street Hospital London, London, England, United Kingdom
- 700 1_
- $a Cougoul, Pierre $u Oncopole, Institut Universitaire du cancer de toulouse, Toulouse, France
- 700 1_
- $a Crickx, Etienne $u Internal Medicine Department, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris-Est Créteil (UPEC), Créteil, France
- 700 1_
- $a Dara, Jasmeen $u Division of Allergy, Immunology, Bone Marrow Transplantation, Department of Pediatrics, University of California, San Francisco, Calif
- 700 1_
- $a Deyà-Martínez, Angela $u Clinical Immunology and Primary Immunodeficiencies Unit, Pediatric Allergy and Clinical Immunology Department, Hospital Sant Joan de Déu, Barcelona, Spain; Universitat de Barcelona Institut de Recerca Sant Joan de Déu, Barcelona, Spain
- 700 1_
- $a Farmand, Susan $u Division of Pediatric Stem Cell Transplantation and Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- 700 1_
- $a Formankova, Renata $u Department of Paediatric Haematology and Oncology, Motol University Hospital and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
- 700 1_
- $a Gennery, Andrew R $u Children's Hematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, England, United Kingdom
- 700 1_
- $a Gonzalez-Granado, Luis Ignacio $u Primary Immunodeficiencies Unit, Department of Pediatrics, Hospital 12 Octubre Research Institute, Hospital 12 Octubre (i+12) Complutense University School of Medicine, Madrid, Spain
- 700 1_
- $a Hagin, David $u Allergy and Clinical Immunology Unit, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel
- 700 1_
- $a Hanitsch, Leif Gunnar $u Institute of Medical Immunology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin and the Berlin Institute of Health (BIH), BIH Center for Regenerative Therapies, Berlin, Germany
- 700 1_
- $a Hanzlikovà, Jana $u Department of Immunology and Allergology, Faculty of Medicine and Faculty Hospital, Pilsen, Czech Republic
- 700 1_
- $a Hauck, Fabian $u Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
- 700 1_
- $a Ivorra-Cortés, José $u Rheumatology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
- 700 1_
- $a Kisand, Kai $u Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia
- 700 1_
- $a Kiykim, Ayca $u Istanbul University-Cerrahpasa, Pediatric Immunology and Allergy, Istanbul, Turkey
- 700 1_
- $a Körholz, Julia $u Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- 700 1_
- $a Leahy, Timothy Ronan $u Children's Health Ireland, Crumlin, Dublin, Ireland; University of Dublin, Trinity College, Dublin, Ireland
- 700 1_
- $a van Montfrans, Joris $u Department of Pediatric Immunology and Infectious Diseases, Wilhelmina's Children Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- 700 1_
- $a Nademi, Zohreh $u Children's Hematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, England, United Kingdom
- 700 1_
- $a Nelken, Brigitte $u Pediatric Hematology Unit, Centre Hospitalier Universitaire Regional de Lille, Lille, France
- 700 1_
- $a Parikh, Suhag $u Aflac Cancer and Blood Disorder Center, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Ga
- 700 1_
- $a Plado, Silvi $u Department of Pediatrics, Tallinn Children's Hospital, Tallinn, Estonia
- 700 1_
- $a Ramakers, Jan $u Department of Pediatrics. Hospital Universitari Son Espases, Palma, Spain; Multidisciplinary Group for Research in Pediatrics, Hospital Universtari Son Espases, Balearic Island Health Research Institute (IdISBa), Palma, Spain
- 700 1_
- $a Redlich, Antje $u Pediatric Oncology Department, Otto von Guericke University Children's Hospital Magdeburg, Magdeburg, Germany
- 700 1_
- $a Rieux-Laucat, Frédéric $u Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, Institut Imagine, INSERM, UMR 1163, Paris, France
- 700 1_
- $a Rivière, Jacques G $u Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- 700 1_
- $a Rodina, Yulia $u Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Moscow, Russia
- 700 1_
- $a Júnior, Pérsio Roxo $u Division of Pediatric Immunology and Allergy, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil
- 700 1_
- $a Salou, Sarah $u Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 700 1_
- $a Schuetz, Catharina $u Department of Pediatrics, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- 700 1_
- $a Shcherbina, Anna $u Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology, and Immunology, Moscow, Russia
- 700 1_
- $a Slatter, Mary A $u Children's Hematopoietic Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, England, United Kingdom
- 700 1_
- $a Touzot, Fabien $u Department of Pediatrics, CHU Ste-Justine, Université de Montréal, Montreal, Canada
- 700 1_
- $a Unal, Ekrem $u Department of Pediatric Hematology and Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey
- 700 1_
- $a Lankester, Arjan C $u Willem-Alexander Children's Hospital, Department of Pediatrics, Pediatric Stem cell Transplantation program, Leiden University Medical Center, Leiden, The Netherlands
- 700 1_
- $a Burns, Siobhan $u Institute of Immunity and Transplantation, University College London, London, England, United Kingdom
- 700 1_
- $a Seppänen, Mikko R J $u The Rare Disease and Pediatric Research Centers, Hospital for Children and Adolescents and Adult Immunodeficiency Unit, Inflammation Center, University of Helsinki and HUS Helsinki, University Hospital, Helsinki, Finland
- 700 1_
- $a Neth, Olaf $u Pediatric Infectious Diseases, Rheumatology and Immunology Unit, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla, IBiS/ Universidad de Sevilla/CSIC, Red de Investigación Traslacional en Infectología Pediátrica RITIP, Seville, Spain
- 700 1_
- $a Albert, Michael H $u Department of Pediatrics, Dr von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany
- 700 1_
- $a Ehl, Stephan $u Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 700 1_
- $a Neven, Bénédicte $u Immuno-hematology and Rheumatology Unit, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris, Université de Paris, INSERM 1163, Institut Imagine, Paris, Île-de-France, France
- 700 1_
- $a Speckmann, Carsten $u Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany; Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: carsten.speckmann@uniklinik-freiburg.de
- 773 0_
- $w MED00002505 $t Journal of allergy and clinical immunology $x 1097-6825 $g Roč. 153, č. 1 (2024), s. 275-286.e18
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/37935260 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y - $z 0
- 990 __
- $a 20240412 $b ABA008
- 991 __
- $a 20240423160259 $b ABA008
- 999 __
- $a ok $b bmc $g 2081666 $s 1217574
- BAS __
- $a 3
- BAS __
- $a PreBMC-MEDLINE
- BMC __
- $a 2024 $b 153 $c 1 $d 275-286.e18 $e 20231105 $i 1097-6825 $m Journal of allergy and clinical immunology $n J Allergy Clin Immunol $x MED00002505
- LZP __
- $a Pubmed-20240412
