Multicenter Study

. 2020 Aug;55(8):1540-1551.

doi: 10.1038/s41409-020-0854-0. Epub 2020 Mar 17.

Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study

Andre Manfred Willasch¹, Christina Peters², Petr Sedláček³, Jean-Hugues Dalle⁴, Vassiliki Kitra-Roussou⁵, Akif Yesilipek⁶, Jacek Wachowiak⁷, Arjan Lankester⁸, Arcangelo Prete⁹, Amir Ali Hamidieh¹⁰, Marianne Ifversen¹¹, Jochen Buechner¹², Gergely Kriván¹³, Rose-Marie Hamladji¹⁴, Cristina Diaz-de-Heredia¹⁵, Elena Skorobogatova¹⁶, Gérard Michel¹⁷, Franco Locatelli^{18

19}, Alice Bertaina^{18

19

20}, Paul Veys²¹, Sophie Dupont²², Reuven Or²³, Tayfun Güngör²⁴, Olga Aleinikova²⁵, Sabina Sufliarska²⁶, Mikael Sundin²⁷, Jelena Rascon²⁸, Ain Kaare²⁹, Damir Nemet³⁰, Franca Fagioli³¹, Thomas Erich Klingebiel³², Jan Styczynski³³, Marc Bierings³⁴, Kálmán Nagy³⁵, Manuel Abecasis³⁶, Boris Afanasyev³⁷, Marc Ansari³⁸, Kim Vettenranta³⁹, Amal Alseraihy⁴⁰, Alicja Chybicka⁴¹, Stephen Robinson⁴², Yves Bertrand⁴³, Alphan Kupesiz⁴⁴, Ardeshir Ghavamzadeh⁴⁵, Antonio Campos⁴⁶, Herbert Pichler², Arnaud Dalissier⁴⁷, Myriam Labopin⁴⁸, Selim Corbacioglu⁴⁹, Adriana Balduzzi⁵⁰, Jacques-Emmanuel Galimard⁴⁷, Peter Bader³²; EBMT Paediatric Diseases Working Party

Affiliations

¹ Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital, Goethe University Frankfurt, Frankfurt, Germany. andre.willasch@kgu.de.
² St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
³ Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic.
⁴ Department of Pediatric Hemato-Immunology, Hôpital Robert Debré and Université de Paris, Paris, France.
⁵ Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Thivon and Papadiamantopoulou, Athens, Greece.
⁶ Department of Pediatric Hematology and Stem Cell Transplantation Unit, Medicalpark Antalya Hastanesi, Antalya, Turkey.
⁷ Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznan, Poland.
⁸ Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
⁹ Hematology-Oncology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna, Bologna, Italy.
¹⁰ Pediatric Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
¹¹ Department of Pediatrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
¹² Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway.
¹³ 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.
¹⁴ Centre Pierre et Marie Curie, Service Hématologie Greffe de Moelle, Alger, Algeria.
¹⁵ Servicio de Hematologia y Oncologia Pediátricas, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
¹⁶ BMT Department, Russian Children's Hospital, Moscow, Russia.
¹⁷ Department of Pediatric Hematology and Oncology and Research Unit EA 3279, Timone Enfants Hospital, AP-HM and Aix-Marseille University, Marseille, France.
¹⁸ Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
¹⁹ Dipartimento Materno-Infantile e Scienze Urologiche, Sapienza University of Rome, Rome, Italy.
²⁰ Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA.
²¹ Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
²² Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
²³ Department of Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
²⁴ Division of Stem Cell Transplantation, Children's Research Center (CRC), University Children's Hospital, Zurich, Switzerland.
²⁵ Republic Clinical Research Centre for Pediatric Oncology and Hematology, Minsk, Belarus.
²⁶ BMT Unit, Department of Pediatric Hematology and Oncology, Comenius University Medical School, Limbová, Bratislava, Slovak Republic.
²⁷ Division of Pediatrics, CLINTEC, Karolinska Institutet and Pediatric Hematology, Immunology and HCT, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
²⁸ Center of Pediatric Oncology and Hematology, Vilnius University, Vilnius, Lithuania.
²⁹ Tartu University Hospital, Tartu, Estonia.
³⁰ Department of Haematology, Internal Clinic, University Hospital Centre, Zagreb, Croatia.
³¹ Paediatric Onco-Haematology, City of Science and Health of Turino, Regina Margherita Children's Hospital, Torino, Italy.
³² Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.
³³ Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland.
³⁴ BMT-Unit, University Medical Centre Utrecht Pediatrics, Utrecht, The Netherlands.
³⁵ Department of Hematology, Child Welfare Center, Borsod County Teaching Hospital, Miskolc, Hungary.
³⁶ Bone Marrow Transplant Program, Instituto Portugues Oncologia, Lisbon, Portugal.
³⁷ Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Haematology and Transplantation, Saint Petersburg State Medical I.P. Pavlov University, Saint Petersburg, Russia.
³⁸ Department of Pediatrics, Onco-Hematology Unit, Geneva University Hospital, Geneva University, Geneva, Switzerland.
³⁹ Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
⁴⁰ Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
⁴¹ Department of Bone Marrow Transplantation, Oncology and Hematology, Cape of Hope Medical Center, Wroclaw Medical University, Wroclaw, Poland.
⁴² University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
⁴³ Department of Pediatric Hematology and BMT, IHOP and Claude Bernard University, Lyon, France.
⁴⁴ Department of Pediatric Hematology-Oncology, School of Medicine, Akdeniz University, Antalya, Turkey.
⁴⁵ Hematology-Oncology and BMT Research, Shariati Hospital, Tehran, Iran.
⁴⁶ Bone Marrow Transplantation Service, Portuguese Institute of Oncology, Porto, Portugal.
⁴⁷ EBMT Paediatric Diseases Working Party, Paris, France.
⁴⁸ EBMT Paris Study Office, Paris, France.
⁴⁹ Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.
⁵⁰ Bone Marrow Transplantation Unit, Pediatric Department of Milano-Bicocca University, Fondazione Monza e Brianza per il Bambino e la sua Mamma Foundation, Monza, Italy.

PMID: 32203263
PMCID: PMC8376634
DOI: 10.1038/s41409-020-0854-0

Multicenter Study

Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study

Andre Manfred Willasch et al. Bone Marrow Transplant. 2020 Aug.

. 2020 Aug;55(8):1540-1551.

doi: 10.1038/s41409-020-0854-0. Epub 2020 Mar 17.

Authors

Affiliations

¹ Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital, Goethe University Frankfurt, Frankfurt, Germany. andre.willasch@kgu.de.
² St. Anna Children's Hospital, Department of Pediatrics, Medical University of Vienna, Vienna, Austria.
³ Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic.
⁴ Department of Pediatric Hemato-Immunology, Hôpital Robert Debré and Université de Paris, Paris, France.
⁵ Stem Cell Transplant Unit, Aghia Sophia Children's Hospital, Thivon and Papadiamantopoulou, Athens, Greece.
⁶ Department of Pediatric Hematology and Stem Cell Transplantation Unit, Medicalpark Antalya Hastanesi, Antalya, Turkey.
⁷ Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznan, Poland.
⁸ Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
⁹ Hematology-Oncology Unit "Lalla Seràgnoli", Department of Pediatrics, University of Bologna, Bologna, Italy.
¹⁰ Pediatric Cell Therapy Research Center, Tehran University of Medical Sciences, Tehran, Iran.
¹¹ Department of Pediatrics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
¹² Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway.
¹³ 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.
¹⁴ Centre Pierre et Marie Curie, Service Hématologie Greffe de Moelle, Alger, Algeria.
¹⁵ Servicio de Hematologia y Oncologia Pediátricas, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
¹⁶ BMT Department, Russian Children's Hospital, Moscow, Russia.
¹⁷ Department of Pediatric Hematology and Oncology and Research Unit EA 3279, Timone Enfants Hospital, AP-HM and Aix-Marseille University, Marseille, France.
¹⁸ Dipartimento di Onco-Ematologia e Terapia Cellulare e Genica, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.
¹⁹ Dipartimento Materno-Infantile e Scienze Urologiche, Sapienza University of Rome, Rome, Italy.
²⁰ Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA.
²¹ Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
²² Department of Pediatric Hematology and Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
²³ Department of Bone Marrow Transplantation, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
²⁴ Division of Stem Cell Transplantation, Children's Research Center (CRC), University Children's Hospital, Zurich, Switzerland.
²⁵ Republic Clinical Research Centre for Pediatric Oncology and Hematology, Minsk, Belarus.
²⁶ BMT Unit, Department of Pediatric Hematology and Oncology, Comenius University Medical School, Limbová, Bratislava, Slovak Republic.
²⁷ Division of Pediatrics, CLINTEC, Karolinska Institutet and Pediatric Hematology, Immunology and HCT, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
²⁸ Center of Pediatric Oncology and Hematology, Vilnius University, Vilnius, Lithuania.
²⁹ Tartu University Hospital, Tartu, Estonia.
³⁰ Department of Haematology, Internal Clinic, University Hospital Centre, Zagreb, Croatia.
³¹ Paediatric Onco-Haematology, City of Science and Health of Turino, Regina Margherita Children's Hospital, Torino, Italy.
³² Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital, Goethe University Frankfurt, Frankfurt, Germany.
³³ Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University Torun, Bydgoszcz, Poland.
³⁴ BMT-Unit, University Medical Centre Utrecht Pediatrics, Utrecht, The Netherlands.
³⁵ Department of Hematology, Child Welfare Center, Borsod County Teaching Hospital, Miskolc, Hungary.
³⁶ Bone Marrow Transplant Program, Instituto Portugues Oncologia, Lisbon, Portugal.
³⁷ Raisa Gorbacheva Memorial Research Institute for Pediatric Oncology, Haematology and Transplantation, Saint Petersburg State Medical I.P. Pavlov University, Saint Petersburg, Russia.
³⁸ Department of Pediatrics, Onco-Hematology Unit, Geneva University Hospital, Geneva University, Geneva, Switzerland.
³⁹ Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
⁴⁰ Department of Pediatric Hematology Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
⁴¹ Department of Bone Marrow Transplantation, Oncology and Hematology, Cape of Hope Medical Center, Wroclaw Medical University, Wroclaw, Poland.
⁴² University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
⁴³ Department of Pediatric Hematology and BMT, IHOP and Claude Bernard University, Lyon, France.
⁴⁴ Department of Pediatric Hematology-Oncology, School of Medicine, Akdeniz University, Antalya, Turkey.
⁴⁵ Hematology-Oncology and BMT Research, Shariati Hospital, Tehran, Iran.
⁴⁶ Bone Marrow Transplantation Service, Portuguese Institute of Oncology, Porto, Portugal.
⁴⁷ EBMT Paediatric Diseases Working Party, Paris, France.
⁴⁸ EBMT Paris Study Office, Paris, France.
⁴⁹ Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.
⁵⁰ Bone Marrow Transplantation Unit, Pediatric Department of Milano-Bicocca University, Fondazione Monza e Brianza per il Bambino e la sua Mamma Foundation, Monza, Italy.

PMID: 32203263
PMCID: PMC8376634
DOI: 10.1038/s41409-020-0854-0

Erratum in

Correction: Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.
Willasch AM, Peters C, Sedláček P, Dalle JH, Kitra-Roussou V, Yesilipek A, Wachowiak J, Lankester A, Prete A, Hamidieh AA, Ifversen M, Buechner J, Kriván G, Hamladji RM, Diaz-de-Heredia C, Skorobogatova E, Michel G, Locatelli F, Bertaina A, Veys P, Dupont S, Or R, Güngör T, Aleinikova O, Sufliarska S, Sundin M, Rascon J, Kaare A, Nemet D, Fagioli F, Klingebiel TE, Styczynski J, Bierings M, Nagy K, Abecasis M, Afanasyev B, Ansari M, Vettenranta K, Alseraihy A, Chybicka A, Robinson S, Bertrand Y, Kupesiz A, Ghavamzadeh A, Campos A, Pichler H, Dalissier A, Labopin M, Corbacioglu S, Balduzzi A, Galimard JE, Bader P; EBMT Paediatric Diseases Working Party. Willasch AM, et al. Bone Marrow Transplant. 2021 Oct;56(10):2615. doi: 10.1038/s41409-021-01424-5. Bone Marrow Transplant. 2021. PMID: 34413474 Free PMC article. No abstract available.

Abstract

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.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

**Fig. 1. Survival by conditioning regimen.**
a Outcomes of patients in CR1. b Outcomes of patients in CR2. CC chemotherapy-based conditioning, CR1 first complete remission, CR2 second complete remission, FTBI fractionated total body irradiation, LFS leukemia-free survival, NRM nonrelapse mortality, OS overall survival, RI relapse incidence.

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Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study

Affiliations

Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study

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