Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.,Bone Marrow Transplantation

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Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.
Bone Marrow Transplantation ( IF 4.5 ) Pub Date : 2020-03-17 , DOI: 10.1038/s41409-020-0854-0
Andre Manfred Willasch ₁ , Christina Peters ₂ , Petr Sedláček ₃ , Jean-Hugues Dalle ₄ , Vassiliki Kitra-Roussou ₅ , Akif Yesilipek ₆ , Jacek Wachowiak ₇ , Arjan Lankester ₈ , Arcangelo Prete ₉ , Amir Ali Hamidieh ₁₀ , Marianne Ifversen ₁₁ , Jochen Buechner ₁₂ , Gergely Kriván ₁₃ , Rose-Marie Hamladji ₁₄ , Cristina Diaz-de-Heredia ₁₅ , Elena Skorobogatova ₁₆ , Gérard Michel ₁₇ , Franco Locatelli _{18,

19} , Alice Bertaina _{18,

19,

20} , Paul Veys ₂₁ , Sophie Dupont ₂₂ , Reuven Or ₂₃ , Tayfun Güngör ₂₄ , Olga Aleinikova ₂₅ , Sabina Sufliarska ₂₆ , Mikael Sundin ₂₇ , Jelena Rascon ₂₈ , Ain Kaare ₂₉ , Damir Nemet ₃₀ , Franca Fagioli ₃₁ , Thomas Erich Klingebiel ₁ , Jan Styczynski ₃₂ , Marc Bierings ₃₃ , Kálmán Nagy ₃₄ , Manuel Abecasis ₃₅ , Boris Afanasyev ₃₆ , Marc Ansari ₃₇ , Kim Vettenranta ₃₈ , Amal Alseraihy ₃₉ , Alicja Chybicka ₄₀ , Stephen Robinson ₄₁ , Yves Bertrand ₄₂ , Alphan Kupesiz ₄₃ , Ardeshir Ghavamzadeh ₄₄ , Antonio Campos ₄₅ , Herbert Pichler ₂ , Arnaud Dalissier ₄₆ , Myriam Labopin ₄₇ , Selim Corbacioglu ₄₈ , Adriana Balduzzi ₄₉ , Jacques-Emmanuel Galimard ₄₆ , Peter Bader ₁ ,

Affiliation

Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.
St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic.
Department of Pediatric Hemato-Immunology, Hôpital Robert Debré and Université de Paris, Paris, France.
Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Thivon and Papadiamantopoulou, Athens, Greece.
Department of Pediatric Hematology and Stem Cell Transplantation Unit, Medicalpark Antalya Hastanesi, Antalya, Turkey.
Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznan, Poland.
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Hematology-Oncology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna, Bologna, Italy.
Pediatric Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pediatrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway.
Department for Pediatric Hematology and Hemopoietic Stem Cell Transplantation, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, United St. Istvan and St. László Hospital, Budapest, Hungary.
Centre Pierre et Marie Curie, Service Hématologie Greffe de Moelle, Alger, Algeria.
Servicio de Hematologia y Oncologia Pediátricas, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
BMT Department, Russian Children's Hospital, Moscow, Russia.
Department of Pediatric Hematology and Oncology and Research Unit EA 3279, Timone Enfants Hospital, AP-HM and Aix-Marseille University, Marseille, France.
Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Dipartimento Materno-Infantile e Scienze Urologiche, Sapienza University of Rome, Rome, Italy.
Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA.
Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
Department of Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Division of Stem Cell Transplantation, Children's Research Center (CRC), University Children's Hospital, Zurich, Switzerland.
Republic Clinical Research Centre for Pediatric Oncology and Hematology, Minsk, Belarus.
BMT Unit, Department of Pediatric Hematology and Oncology, Comenius University Medical School, Limbová, Bratislava, Slovak Republic.
Division of Pediatrics, CLINTEC, Karolinska Institutet and Pediatric Hematology, Immunology and HCT, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Center of Pediatric Oncology and Hematology, Vilnius University, Vilnius, Lithuania.
Tartu University Hospital, Tartu, Estonia.
Department of Haematology, Internal Clinic, University Hospital Centre, Zagreb, Croatia.
Paediatric Onco-Haematology, City of Science and Health of Turino, Regina Margherita Children's Hospital, Torino, Italy.
Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland.
BMT-Unit, University Medical Centre Utrecht Pediatrics, Utrecht, The Netherlands.
Department of Hematology, Child Welfare Center, Borsod County Teaching Hospital, Miskolc, Hungary.
Bone Marrow Transplant Program, Instituto Portugues Oncologia, Lisbon, Portugal.
Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Haematology and Transplantation, Saint Petersburg State Medical I.P. Pavlov University, Saint Petersburg, Russia.
Department of Pediatrics, Onco-Hematology Unit, Geneva University Hospital, Geneva University, Geneva, Switzerland.
Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
Department of Bone Marrow Transplantation, Oncology and Hematology, Cape of Hope Medical Center, Wroclaw Medical University, Wroclaw, Poland.
University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
Department of Pediatric Hematology and BMT, IHOP and Claude Bernard University, Lyon, France.
Department of Pediatric Hematology-Oncology, School of Medicine, Akdeniz University, Antalya, Turkey.
Hematology-Oncology and BMT Research, Shariati Hospital, Tehran, Iran.
Bone Marrow Transplantation Service, Portuguese Institute of Oncology, Porto, Portugal.
EBMT Paediatric Diseases Working Party, Paris, France.
EBMT Paris Study Office, Paris, France.
Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.
Bone Marrow Transplantation Unit, Pediatric Department of Milano-Bicocca University, Fondazione Monza e Brianza per il Bambino e la sua Mamma Foundation, Monza, Italy.

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2–18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective “real-world-practice” study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.

中文翻译：

儿科 ALL 中异基因 HSCT 的清髓调理：FTBI 还是化疗？ - 一项多中心 EBMT-PDWP 研究。

尽管大多数急性淋巴细胞白血病 (ALL) 儿童接受分次全身照射 (FTBI) 作为同种异体造血干细胞移植 (allo-HSCT) 的清髓预处理 (MAC)，但化疗能否有效替代 FTBI 仍是一个重要的争论问题。为了比较 FTBI 与基于化疗的调理 (CC) 后的结果，我们进行了一项回顾性 EBMT 注册研究。MAC 后 2-18 岁的儿童在第一次 (CR1) 或第二次缓解 (CR2) 中对来自匹配相关 (MRD) 或无关供体 (UD) 的骨髓 (BM) 或外周血干细胞 (PBSC) 进行首次同种异体 HSCT ）2000 年至 2012 年期间的数据也包括在内。倾向评分加权用于控制观察变量的治疗前不平衡。分析了 3.054 名患者。CR1 (1.498)：FTBI 后中位随访 (FU) (1. 285）和CC（213）分别为6.8和6.1年。生存率没有显着差异。CR2 (1.556)：FTBI (1.345) 和 CC (211) 后的中位 FU 为 6.2 年。与 CC 相比，FTBI 后的结果在总生存期 (OS)、无白血病生存期 (LFS)、复发率 (RI) 和非复发死亡率 (NRM) 方面均优于 CC。然而，我们必须强调这项回顾性“现实世界实践”研究结果的初步特征。这些发现将在 ALL SCTped 2012 FORUM 试验中进行前瞻性评估。我们必须强调这项回顾性“现实世界实践”研究结果的初步特征。这些发现将在 ALL SCTped 2012 FORUM 试验中进行前瞻性评估。我们必须强调这项回顾性“现实世界实践”研究结果的初步特征。这些发现将在 ALL SCTped 2012 FORUM 试验中进行前瞻性评估。

更新日期：2020-04-24

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