Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM
Abstract: The superiority of total body irradiation (TBI)–based vs chemotherapy conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL) has been established in the international, prospective phase-3 FORUM study, randomizing...
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Elsevier
2025-02-01
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| Series: | Blood Advances |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2473952924006803 |
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| author | Krzysztof Kalwak Laura M. Moser Ulrike Pötschger Peter Bader Katharina Kleinschmidt Roland Meisel Jean-Hugues Dalle Akif Yesilipek Adriana Balduzzi Gergely Krivan Evgenios Goussetis Raquel Staciuk Petr Sedlacek Herbert Pichler Peter Svec Melissa Gabriel Tayfun Güngör Ernest Bilic Jochen Buechner Marleen Renard Kim Vettenranta Marianne Ifversen Cristina Diaz-de-Heredia Jerry Stein Jacek Toporski Marc Bierings Christina Peters Marc Ansari Franco Locatelli |
| author_facet | Krzysztof Kalwak Laura M. Moser Ulrike Pötschger Peter Bader Katharina Kleinschmidt Roland Meisel Jean-Hugues Dalle Akif Yesilipek Adriana Balduzzi Gergely Krivan Evgenios Goussetis Raquel Staciuk Petr Sedlacek Herbert Pichler Peter Svec Melissa Gabriel Tayfun Güngör Ernest Bilic Jochen Buechner Marleen Renard Kim Vettenranta Marianne Ifversen Cristina Diaz-de-Heredia Jerry Stein Jacek Toporski Marc Bierings Christina Peters Marc Ansari Franco Locatelli |
| author_sort | Krzysztof Kalwak |
| collection | DOAJ |
| description | Abstract: The superiority of total body irradiation (TBI)–based vs chemotherapy conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL) has been established in the international, prospective phase-3 FORUM study, randomizing 417 patients aged 4-18 years in complete remission (CR), who received allo-HSCT from HLA-matched sibling or unrelated donors. Because of the unavailability of TBI in some regions and to accommodate individual contraindications, this study reports the prespecified comparison of outcomes of patients receiving busulfan (BU)– or treosulfan (TREO)–based regimens from 2013 to 2018. Overall, 180 and 128 patients received BU/thiotepa (THIO)/fludarabine (FLU) or TREO/THIO/FLU, respectively. Data were analyzed as of February 2023, with a median follow-up of 4.2 years (range, 0.3-9.1). 3-year overall survival was 0.71 (BU, 95% confidence interval [0.64-0.77]) and 0.72 (TREO, [0.63-0.79]) and 3-year event-free survival was 0.60 (BU, [0.53-0.67]) and 0.55 (TREO, [0.46-0.63]). The 3-year cumulative incidence of relapse (BU, 0.31 [0.25-0.38]; TREO, 0.36 [0.27-0.44]); and nonrelapse mortality (BU, 0.08 [0.05-0.13]; TREO, 0.09 [0.05-0.15]) were comparable. One case of fatal veno-occlusive disease occurred in each group. No significant differences in acute and chronic graft-versus-host disease (GVHD) or 3-year GVHD-free and relapse-free survival (BU, 0.48 [0.41-0.55]; TREO, 0.45 [0.37-0.54]) were recorded. Outcomes for patients in first and second CR were similar irrespective of the regimen. In conclusion, BU/THIO/FLU or TREO/THIO/FLU regimens can be an alternative to TBI for patients with ALL aged >4 years with contraindications or lack of access to TBI. This trial was registered at www.ClinicalTrials.gov as #NCT01949129. |
| format | Article |
| id | doaj-art-65df548ef3f24bb1b914e161da1cc000 |
| institution | Kabale University |
| issn | 2473-9529 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Advances |
| spelling | doaj-art-65df548ef3f24bb1b914e161da1cc0002025-02-12T05:31:37ZengElsevierBlood Advances2473-95292025-02-0194741751Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUMKrzysztof Kalwak0Laura M. Moser1Ulrike Pötschger2Peter Bader3Katharina Kleinschmidt4Roland Meisel5Jean-Hugues Dalle6Akif Yesilipek7Adriana Balduzzi8Gergely Krivan9Evgenios Goussetis10Raquel Staciuk11Petr Sedlacek12Herbert Pichler13Peter Svec14Melissa Gabriel15Tayfun Güngör16Ernest Bilic17Jochen Buechner18Marleen Renard19Kim Vettenranta20Marianne Ifversen21Cristina Diaz-de-Heredia22Jerry Stein23Jacek Toporski24Marc Bierings25Christina Peters26Marc Ansari27Franco Locatelli28Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation, Wroclaw Medical University, Wroclaw, PolandDivision for Stem Cell Transplantation and Immunology, Department of Pediatrics, Goethe University Frankfurt, University Hospital, Frankfurt, Germany; Correspondence: Laura M. Moser, Goethe University Frankfurt, University Hospital, Department of Pediatrics, Division for Stem Cell Transplantation and Immunology, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany;St. Anna Children’s Cancer Research Institute, Vienna, AustriaDivision for Stem Cell Transplantation and Immunology, Department of Pediatrics, Goethe University Frankfurt, University Hospital, Frankfurt, GermanyDepartment of Pediatric Hematology, Oncology, and Stem Cell Transplantation, University Children’s Hospital Regensburg, Regensburg, GermanyDivision of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf, GermanyPediatric Hematology and Immunology Department, Robert Debré Hospital, Groupe Hospitalo-Universitaire Assistance Publique Hôpitaux de Paris Nord, Université Paris Cité, Paris, FranceMedical Park Antalya Hospital, Antalya, TurkeySchool of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; Pediatric Hematopoietic Stem Cell Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, ItalyPediatric Hematology and Stem Cell Transplantation Department, National Institute of Hematology and Infectious Diseases, Central Hospital of Southern Pest, Budapest, HungaryStem Cell Transplant Unit, Agia Sofia Children's Hospital, Athens, GreeceHospital de Pediatría “Prof. Dr Juan P. Garrahan,” Buenos Aires, ArgentinaDepartment of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech RepublicSt. Anna Children’s Cancer Research Institute, Vienna, Austria; Department of Pediatric Hematology and Oncology, St. Anna Children’s Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Pediatric Hematology and Oncology, National Institute of Children’s Diseases, Comenius University, Bratislava, SlovakiaThe Children’s Hospital at Westmead, Sidney, NSW, AustraliaDivision of Hematology/Oncology/Immunology, Gene Therapy, and Stem Cell Transplantation, University Children's Hospital Zurich, Eleonore Foundation and Children’s Research Center, Zürich, SwitzerlandDivision for Hematology and Oncology, Department of Pediatrics Zagreb, University Hospital Center, Zagreb, CroatiaDepartment of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, NorwayDepartment of Paediatric Oncology, University Hospital Leuven, Leuven, BelgiumUniversity of Helsinki and the Hospital for Children and Adolescents, University of Helsinki, Helsinki, FinlandDepartment of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, DenmarkDivision of Pediatric Hematology and Oncology, Hospital Universitari Vall d'Hebron, Barcelona, SpainSchneider Children's Medical Center of Israel and Sackler Faculty of Medicine Tel Aviv University, Petah Tikva, IsraelDepartment Cell Therapy and Allogeneic Stem Cell Transplant, Karolinska University Hospital, Stockholm, SwedenPrincess Máxima Center for Pediatric Oncology, Utrecht, The NetherlandsSt. Anna Children’s Cancer Research Institute, Vienna, Austria; Department of Pediatric Hematology and Oncology, St. Anna Children’s Hospital, Medical University of Vienna, Vienna, AustriaCANSEARCH Research Platform for Pediatric Oncology and Hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland; Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Geneva Hospitals, Geneva, SwitzerlandDepartment of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, ItalyAbstract: The superiority of total body irradiation (TBI)–based vs chemotherapy conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL) has been established in the international, prospective phase-3 FORUM study, randomizing 417 patients aged 4-18 years in complete remission (CR), who received allo-HSCT from HLA-matched sibling or unrelated donors. Because of the unavailability of TBI in some regions and to accommodate individual contraindications, this study reports the prespecified comparison of outcomes of patients receiving busulfan (BU)– or treosulfan (TREO)–based regimens from 2013 to 2018. Overall, 180 and 128 patients received BU/thiotepa (THIO)/fludarabine (FLU) or TREO/THIO/FLU, respectively. Data were analyzed as of February 2023, with a median follow-up of 4.2 years (range, 0.3-9.1). 3-year overall survival was 0.71 (BU, 95% confidence interval [0.64-0.77]) and 0.72 (TREO, [0.63-0.79]) and 3-year event-free survival was 0.60 (BU, [0.53-0.67]) and 0.55 (TREO, [0.46-0.63]). The 3-year cumulative incidence of relapse (BU, 0.31 [0.25-0.38]; TREO, 0.36 [0.27-0.44]); and nonrelapse mortality (BU, 0.08 [0.05-0.13]; TREO, 0.09 [0.05-0.15]) were comparable. One case of fatal veno-occlusive disease occurred in each group. No significant differences in acute and chronic graft-versus-host disease (GVHD) or 3-year GVHD-free and relapse-free survival (BU, 0.48 [0.41-0.55]; TREO, 0.45 [0.37-0.54]) were recorded. Outcomes for patients in first and second CR were similar irrespective of the regimen. In conclusion, BU/THIO/FLU or TREO/THIO/FLU regimens can be an alternative to TBI for patients with ALL aged >4 years with contraindications or lack of access to TBI. This trial was registered at www.ClinicalTrials.gov as #NCT01949129.http://www.sciencedirect.com/science/article/pii/S2473952924006803 |
| spellingShingle | Krzysztof Kalwak Laura M. Moser Ulrike Pötschger Peter Bader Katharina Kleinschmidt Roland Meisel Jean-Hugues Dalle Akif Yesilipek Adriana Balduzzi Gergely Krivan Evgenios Goussetis Raquel Staciuk Petr Sedlacek Herbert Pichler Peter Svec Melissa Gabriel Tayfun Güngör Ernest Bilic Jochen Buechner Marleen Renard Kim Vettenranta Marianne Ifversen Cristina Diaz-de-Heredia Jerry Stein Jacek Toporski Marc Bierings Christina Peters Marc Ansari Franco Locatelli Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM Blood Advances |
| title | Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM |
| title_full | Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM |
| title_fullStr | Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM |
| title_full_unstemmed | Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM |
| title_short | Comparable outcomes after busulfan- or treosulfan-based conditioning for allo-HSCT in children with ALL: results of FORUM |
| title_sort | comparable outcomes after busulfan or treosulfan based conditioning for allo hsct in children with all results of forum |
| url | http://www.sciencedirect.com/science/article/pii/S2473952924006803 |
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