Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis

doi:10.1182/blood.2021014687

. 2022 Mar 31;139(13):2066-2079.

doi: 10.1182/blood.2021014687.

Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis

Michael H Albert¹, Mary A Slatter^{2

3}, Andrew R Gennery^{2

3}, Tayfun Güngör⁴, Katerina Bakunina⁵, Benyamin Markovitch⁵, Sheree Hazelaar⁵, Tiarlan Sirait⁵, Virginie Courteille⁶, Alessandro Aiuti^{7

8}, Olga V Aleinikova⁹, Dmitry Balashov¹⁰, Maria Ester Bernardo^{7

8}, Ivana Bodova^{11

12}, Benedicte Bruno¹³, Marina Cavazzana^{14

15}, Robert Chiesa¹⁶, Alain Fischer^{15

17}, Fabian Hauck¹, Marianne Ifversen¹⁸, Krzysztof Kałwak¹⁹, Christoph Klein¹, Alexander Kulagin²⁰, Alphan Kupesiz²¹, Baris Kuskonmaz²², Caroline A Lindemans^{23

24}, Franco Locatelli²⁵, Su Han Lum², Alexey Maschan¹⁰, Roland Meisel²⁶, Despina Moshous^{15

27}, Fulvio Porta²⁸, Martin G Sauer²⁹, Petr Sedlacek³⁰, Ansgar Schulz³¹, Felipe Suarez^{15

32}, Tanja C Vallée¹, Jacek H Winiarski³³, Marco Zecca³⁴, Bénédicte Neven^{15

27}, Paul Veys^{16

35}, Arjan C Lankester³⁶

Affiliations

¹ Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
² Paediatric Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
³ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
⁴ Hematology/Oncology/Immunology, Gene Therapy, and Stem Cell Transplantation, University Children's Hospital Zurich-Eleonore Foundation & Children's Research Center, Zürich, Switzerland.
⁵ Statistical and Study Unit, EBMT office, Leiden, The Netherlands.
⁶ CEREDIH, SCETIDE, Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
⁷ Pediatric Immunohematology, IRCCS Ospedale San Raffaele, Milan, Italy.
⁸ Vita Salute San Raffaele University, Milan, Italy.
⁹ Scientific Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Borovlyany, Minsk Region, Belarus.
¹⁰ Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russian Federation.
¹¹ Bone Marrow Transplantation Unit, National Institute of Children's Diseases, Bratislava, Slovakia.
¹² Department of Pediatric Hematology and Oncology, Comenius University, Bratislava, Slovakia.
¹³ Pediatric Hematology, CHU Lille, Lille, France.
¹⁴ Biotherapy Department and Clinical Investigation Center, Assistance Publique Hôpitaux de Paris, Paris, France.
¹⁵ IMAGINE Institute, Université de Paris, Sorbonne Paris Cité, Paris, France.
¹⁶ Bone Marrow Transplant Department, Great Ormond Street Hospital For Sick Children, London, England.
¹⁷ Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
¹⁸ Department for Children and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁹ Clinical Department of Paediatric Bone Marrow Transplantation, Oncology and Haematology, Wroclaw Medical University, Wroclaw, Poland.
²⁰ RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russian Federation.
²¹ Pediatric Hematology Oncology, Akdeniz University School of Medicine, Antalya, Turkey.
²² Department of Pediatrics, BMT Unit, Hacettepe University, Faculty of Medicine, Ankara, Turkey.
²³ Princess Máxima Center, Utrecht, The Netherlands.
²⁴ Department of Pediatric Hematoloy/Oncology, Cell and Gene Therapy, University Medical Center, University Utrecht, Utrecht, The Netherlands.
²⁵ Department of Pediatric Hematoloy/Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Sapienza University, Rome, Italy.
²⁶ Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
²⁷ Pediatric Immunology, Hematology and Rheumatology Department, Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
²⁸ Pediatric Oncohaematology and BMT, Children's Hospital, Brescia, Italy.
²⁹ Pediatric Hematology and Oncology, MHH, Hannover, Germany.
³⁰ Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic.
³¹ Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
³² Adult Hematology, Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
³³ Department of Pediatrics, Karolinska University Hospital Huddinge, Clintec, Karolinska Institutet, Stockholm, Sweden.
³⁴ Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
³⁵ University College London, GOS Institute of Child Health, London, England; and.
³⁶ Department of Pediatrics, Pediatric Stem Cell Transplantation Program, Willem-Alexander Children's Hospital, Leiden University Medical Center, The Netherlands.

PMID: 35100336
DOI: 10.1182/blood.2021014687

Free article

Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis

Michael H Albert et al. Blood. 2022.

Free article

. 2022 Mar 31;139(13):2066-2079.

doi: 10.1182/blood.2021014687.

Authors

Affiliations

¹ Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, Ludwig-Maximilians-Universität München, Munich, Germany.
² Paediatric Stem Cell Transplant Unit, Great North Children's Hospital, Newcastle upon Tyne, United Kingdom.
³ Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
⁴ Hematology/Oncology/Immunology, Gene Therapy, and Stem Cell Transplantation, University Children's Hospital Zurich-Eleonore Foundation & Children's Research Center, Zürich, Switzerland.
⁵ Statistical and Study Unit, EBMT office, Leiden, The Netherlands.
⁶ CEREDIH, SCETIDE, Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
⁷ Pediatric Immunohematology, IRCCS Ospedale San Raffaele, Milan, Italy.
⁸ Vita Salute San Raffaele University, Milan, Italy.
⁹ Scientific Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Borovlyany, Minsk Region, Belarus.
¹⁰ Department of Hematopoietic Stem Cell Transplantation, Dmitriy Rogachev National Center for Pediatric Hematology, Oncology, and Immunology, Moscow, Russian Federation.
¹¹ Bone Marrow Transplantation Unit, National Institute of Children's Diseases, Bratislava, Slovakia.
¹² Department of Pediatric Hematology and Oncology, Comenius University, Bratislava, Slovakia.
¹³ Pediatric Hematology, CHU Lille, Lille, France.
¹⁴ Biotherapy Department and Clinical Investigation Center, Assistance Publique Hôpitaux de Paris, Paris, France.
¹⁵ IMAGINE Institute, Université de Paris, Sorbonne Paris Cité, Paris, France.
¹⁶ Bone Marrow Transplant Department, Great Ormond Street Hospital For Sick Children, London, England.
¹⁷ Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
¹⁸ Department for Children and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁹ Clinical Department of Paediatric Bone Marrow Transplantation, Oncology and Haematology, Wroclaw Medical University, Wroclaw, Poland.
²⁰ RM Gorbacheva Research Institute, Pavlov University, St. Petersburg, Russian Federation.
²¹ Pediatric Hematology Oncology, Akdeniz University School of Medicine, Antalya, Turkey.
²² Department of Pediatrics, BMT Unit, Hacettepe University, Faculty of Medicine, Ankara, Turkey.
²³ Princess Máxima Center, Utrecht, The Netherlands.
²⁴ Department of Pediatric Hematoloy/Oncology, Cell and Gene Therapy, University Medical Center, University Utrecht, Utrecht, The Netherlands.
²⁵ Department of Pediatric Hematoloy/Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Sapienza University, Rome, Italy.
²⁶ Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
²⁷ Pediatric Immunology, Hematology and Rheumatology Department, Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
²⁸ Pediatric Oncohaematology and BMT, Children's Hospital, Brescia, Italy.
²⁹ Pediatric Hematology and Oncology, MHH, Hannover, Germany.
³⁰ Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic.
³¹ Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
³² Adult Hematology, Necker-Enfants Malades University Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.
³³ Department of Pediatrics, Karolinska University Hospital Huddinge, Clintec, Karolinska Institutet, Stockholm, Sweden.
³⁴ Pediatric Hematology/Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
³⁵ University College London, GOS Institute of Child Health, London, England; and.
³⁶ Department of Pediatrics, Pediatric Stem Cell Transplantation Program, Willem-Alexander Children's Hospital, Leiden University Medical Center, The Netherlands.

PMID: 35100336
DOI: 10.1182/blood.2021014687

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.

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Towards a standard of care in transplant for WAS.
Prockop SE. Prockop SE. Blood. 2022 Mar 31;139(13):1935-1936. doi: 10.1182/blood.2022015612. Blood. 2022. PMID: 35357483 No abstract available.

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Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis

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Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis

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