Victoria Katharina Tesch1, Hassan Abolhassani2, Bella Shadur3, Joachim Zobel4, Yuliya Mareika5, Svetlana Sharapova6, Elif Karakoc-Aydiner7, Jacques G Rivière8, Marina Garcia-Prat8, Nicolette Moes9, Filomeen Haerynck10, Luis I Gonzales-Granado11, Juan Luis Santos Pérez12, Anna Mukhina13, Anna Shcherbina13, Asghar Aghamohammadi14, Lennart Hammarström15, Figen Dogu16, Sule Haskologlu16, Aydan I İkincioğulları16, Sevgi Köstel Bal17, Safa Baris7, Sara Sebnem Kilic18, Neslihan Edeer Karaca19, Necil Kutukculer19, Hermann Girschick20, Antonios Kolios21, Sevgi Keles22, Vedat Uygun22, Polina Stepensky23, Austen Worth24, Joris M van Montfrans25, Anke M J Peters26, Isabelle Meyts27, Mehdi Adeli28, Antonio Marzollo29, Nurcicek Padem30, Amer M Khojah30, Zahra Chavoshzadeh31, Magdalena Avbelj Stefanija32, Shahrzad Bakhtiar33, Benoit Florkin34, Marie Meeths35, Laura Gamez36, Bodo Grimbacher37, Mikko R J Seppänen38, Arjan Lankester39, Andrew R Gennery40, Markus G Seidel41. 1. Research Unit for Pediatric Hematology and Immunology, Medical University Graz, Graz, Austria; Division of Pediatric Hemato-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria. 2. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran. 3. Department of Bone Marrow Transplantation, Hadassah, Hebrew University Medical Centre, Jerusalem, Israel; Garvan Institute of Medical Research, Department of Immunology, Darlinghurst, Australia. 4. Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria. 5. Bone Marrow Transplantation Unit, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus. 6. Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Belarus. 7. Faculty of Medicine, Pediatric Immunology and Allergy Division, Marmara University, Istanbul, Turkey; Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey. 8. Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; Jeffrey Modell Foundation Excellence Center, Barcelona, Spain. 9. Department of Pediatric Gastroenterology, Antwerp University Hospital, Edegem, and Laboratory of Experimental Medicine and Pediatrics, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium. 10. Primary Immune Deficiency Research Lab and Department of Internal Medicine and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Ghent, Belgium. 11. Immunodeficiencies Unit, Hospital 12 de Octubre, Research Institute Hospital 12 Octubre (i+12), Madrid, Spain. 12. Infectious Diseases and Immunodeficiencies Unit, Service of Pediatrics, Hospital Universitario Virgen de las Nieves, Granada, Spain. 13. Immunology, the Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. 14. Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran. 15. Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden. 16. Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey. 17. Department of Pediatric Immunology and Allergy, Ankara University School of Medicine, Ankara, Turkey; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases, Vienna, Austria; CeMM Research Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria. 18. Pediatric Immunology-Rheumatology, Medical Faculty Department of Pediatrics, Uludag University Bursa, Bursa, Turkey. 19. Ege University Faculty of Medicine, Department of Pediatric Immunology, Izmir, Turkey. 20. Children's Hospital, Vivantes Berlin Friedrichshain, Berlin, Germany. 21. Department of Immunology, University Hospital Zurich and University of Zurich, Zurich, Switzerland. 22. Meram Medical Faculty, Division of Pediatric Allergy and Immunology, Necmettin Erbakan University, Konya, Turkey. 23. Department of Bone Marrow Transplantation, Hadassah, Hebrew University Medical Centre, Jerusalem, Israel. 24. Institute of Child Health, University College London, London, United Kingdom. 25. Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, UMC Utrecht, The Netherlands. 26. Department of Pediatric Hematology and Oncology, Center for Pediatrics, Medical Center-University of Freiburg, Freiburg, Germany. 27. Department of Pediatrics, University Hospitals Leuven, and the Laboratory for Inborn Errors of Immunity, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium. 28. Sidra Medicine/Hamad Medical Corporation, Doha, Qatar. 29. Pediatric Hematology-Oncology Unit, Department of Women's and Children's Health, Azienda Ospedaliera-University of Padova, Padova, Italy. 30. Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Ill. 31. Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 32. Department of Pediatric Endocrinology, Diabetes and Metabolism, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia. 33. Division for Stem Cell Transplantation and Immunology, University Hospital Frankfurt, Frankfurt, Germany. 34. Immuno-Hémato-Rhumatologie Pédiatrique, Service de Pédiatrie, CHR Citadelle, Liege, Belgium. 35. Childhood Cancer Research Unit, Department of Women's and Children's Health and Clinical Genetics Unit, Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska Institute, Karolinska University Hospital Solna, Stockholm, Sweden. 36. Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany. 37. Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany; DZIF-German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany; Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany; RESIST-Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany. 38. Rare Diseases Center and Pediatric Research Center, Children and Adolescents, University of Helsinki and HUS Helsinki University Hospital, Helsinki, Finland; Adult Immunodeficiency Unit, Inflammation Center, University of Helsinki, and HUS Helsinki University Hospital, Helsinki, Finland; Translational Immunology, Research Programs Unit and Clinicum, University of Helsinki, Helsinki, Finland. 39. Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands. 40. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom. 41. Research Unit for Pediatric Hematology and Immunology, Medical University Graz, Graz, Austria; Division of Pediatric Hemato-Oncology, Department of Pediatrics and Adolescent Medicine, Medical University Graz, Graz, Austria. Electronic address: markus.seidel@medunigraz.at.
Abstract
BACKGROUND: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. OBJECTIVE: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. METHOD: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. RESULTS: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. CONCLUSION: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.
BACKGROUND: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant. OBJECTIVE: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant. METHOD: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices. RESULTS: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome. CONCLUSION: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT.
Authors: Raki Sudan; Sandra Fernandes; Neetu Srivastava; Chiara Pedicone; Shea T Meyer; John D Chisholm; Robert W Engelman; William G Kerr Journal: Front Immunol Date: 2022-05-04 Impact factor: 8.786
Authors: M Jamee; S Hosseinzadeh; N Sharifinejad; M Zaki-Dizaji; M Matloubi; M Hasani; S Baris; M Alsabbagh; B Lo; G Azizi Journal: Clin Exp Immunol Date: 2021-05-03 Impact factor: 5.732
Authors: Anh N L Phan; Thuy T T Pham; Nghia Huynh; Tuan M Nguyen; Cuc T T Cao; Duong T Nguyen; Duc T Le; Chi-Bao Bui Journal: Mol Genet Genomic Med Date: 2020-03-10 Impact factor: 2.183