Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM Trial
In the randomized cohort of the international phase-III FORUM trial, which showed the superiority of total-body irradiation (TBI) over chemotherapy-based conditioning prior to hematopoietic stem cell transplantation (HSCT) for pediatric acute lymphoblastic leukemia (ALL), type of conditioning and r...
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Ferrata Storti Foundation
2025-08-01
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| Series: | Haematologica |
| Online Access: | https://haematologica.org/article/view/12206 |
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| author | Adriana Balduzzi Evgenia Glogova Christina Peters Petr Sedlacek Jean-Hugues Dalle Franco Locatelli Roland Meisel Birgit Burkhardt Jochen Buechner Jacek Wachowiak Marc Bierings Raquel Staciuk Stelios Graphakos Tayfun Güngör Akif Yesilipek Peter Svec Julia Palma Gergely Krivan Cristina Diaz-de-Heredia Francesca Limido Marc Ansari Krzysztof Kalwak Peter Bader Marianne Ifversen |
| author_facet | Adriana Balduzzi Evgenia Glogova Christina Peters Petr Sedlacek Jean-Hugues Dalle Franco Locatelli Roland Meisel Birgit Burkhardt Jochen Buechner Jacek Wachowiak Marc Bierings Raquel Staciuk Stelios Graphakos Tayfun Güngör Akif Yesilipek Peter Svec Julia Palma Gergely Krivan Cristina Diaz-de-Heredia Francesca Limido Marc Ansari Krzysztof Kalwak Peter Bader Marianne Ifversen |
| author_sort | Adriana Balduzzi |
| collection | DOAJ |
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In the randomized cohort of the international phase-III FORUM trial, which showed the superiority of total-body irradiation (TBI) over chemotherapy-based conditioning prior to hematopoietic stem cell transplantation (HSCT) for pediatric acute lymphoblastic leukemia (ALL), type of conditioning and remission phase, but not pre-HSCT minimal residual disease (MRD), were associated with outcome. We report the impact of MRD within the extended FORUM cohort.
Patients (n=1014), 4–21 years old, transplanted from a matched donor who had ≥1 MRD measurement prior to and/or 100 days and/or 1 year after HSCT were eligible. A threshold of 0.01% defined MRD positivity versus negativity.
Prior to HSCT, 21% of patients were MRDpos. Three-year event-free survival (EFS) was 0.73 and 0.59 (p<0.001), and 3-year cumulative incidence of relapse (CIR) was 0.20 and 0.33 (p<0.001) in MRDneg and MRDpos patients, respectively. The level of MRD positivity pre-HSCT (<0.1% versus ≥0.1%), did not significantly affect outcome. Pre-HSCT MRDneg and TBI/etoposide conditioning were associated with a 2-fold lower risk of relapse, whereas MRDpos had a 2-fold higher risk of any failure and/or death. No detrimental effect of MRDpos pre-HSCT could be demonstrated in patients with T-cell ALL. MRDpos versus MRDneg patients at day 100 had an EFS of 0.47 versus 0.77 (p<0.001) and a CIR of 0.51 versus 0.17 (p<0.001), respectively, but post-HSCT MRDpos did not necessarily imply relapse. In conclusion, the MRD status pre-HSCT and at day 100 post-HSCT was a strong prognostic factor for children transplanted for ALL in the extended FORUM cohort.
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| format | Article |
| id | doaj-art-128fb8c8afff478a86ff63355d3d2bd1 |
| institution | Kabale University |
| issn | 0390-6078 1592-8721 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Ferrata Storti Foundation |
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| series | Haematologica |
| spelling | doaj-art-128fb8c8afff478a86ff63355d3d2bd12025-08-20T03:40:07ZengFerrata Storti FoundationHaematologica0390-60781592-87212025-08-01999110.3324/haematol.2025.287456Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM TrialAdriana Balduzzi0Evgenia Glogova1Christina Peters2Petr Sedlacek3Jean-Hugues Dalle4Franco Locatelli5Roland Meisel6Birgit Burkhardt7Jochen Buechner8Jacek Wachowiak9Marc Bierings10Raquel Staciuk11Stelios Graphakos12Tayfun Güngör13Akif Yesilipek14Peter Svec15Julia Palma16Gergely Krivan17Cristina Diaz-de-Heredia18Francesca Limido19Marc Ansari20Krzysztof Kalwak21Peter Bader22Marianne Ifversen23Pediatric Department, Fondazione IRCCS San Gerardo, Monza, Italy; School of Medicine and Surgery, Milano-Bicocca University, MonzaSt. Anna Children’s Cancer Research Institute, ViennaSt. Anna Children’s Cancer Research Institute, Vienna, Austria; St. Anna Children's Hospital, Medical University Vienna, ViennaDepartment of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech RepublicHemato-Immunology Department, Robert-Debré Hospital, GHU AP-HP Nord, Paris, France; Université Paris Cité, ParisDepartment of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale Pediatrico Bambino Gesù, Roma, Italy; Catholic University of the Sacred Heart, RomeDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Division of Pediatric Stem Cell Therapy, Medical Faculty, Heinrich Heine University, DuesseldorfDepartment of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, MuensterDepartment of Pediatric Hematology and Oncology, Oslo University Hospital, OsloDepartment of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, PoznańPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Utrecht University Children's Hospital, UtrechtHospital de Pediatría “Prof. Dr. Juan P. Garrahan,” Buenos Aires, and Hospital Sor Maria Ludovica, La Plata, Buenos AiresAghia Sophia Children's University Hospital, AthensEleonore Foundation & Children’s Research Center, ZürichPediatric Stem Cell Transplantation Unit, Antalya Medical park Hospital AntalyaDepartment of Pediatric Hematology and Oncology, National Institute of Children’s Diseases, Comenius University, BratislavaFaculty of Medicine, Hospital Luis Calvo Mackenna, Department of Pediatrics-Bone Marrow Transplantation Unit, University of Chile, SantiagoPediatric Hematology and Stem Cell Transplantation Department, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, BudapestDivision of Pediatric Hematology and Oncology, University Hospital Vall d′Hebron, BarcelonaSchool of Medicine and Surgery, Milano-Bicocca University, MonzaCANSEARCH Research Platform for Pediatric Oncology and Hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Switzerland; Department of Women, Child and Adolescent, Division of Pediatric Oncology and Hematology, University Geneva Hospitals, GenevaDepartment of Pediatric Hematology/Oncology and BMT, Wroclaw Medical University, WroclawDepartment of Pediatrics, Division for Stem Cell Transplantation, Immunology, Goethe University, University Hospital Frankfurt am MainDepartment of Pediatric and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital In the randomized cohort of the international phase-III FORUM trial, which showed the superiority of total-body irradiation (TBI) over chemotherapy-based conditioning prior to hematopoietic stem cell transplantation (HSCT) for pediatric acute lymphoblastic leukemia (ALL), type of conditioning and remission phase, but not pre-HSCT minimal residual disease (MRD), were associated with outcome. We report the impact of MRD within the extended FORUM cohort. Patients (n=1014), 4–21 years old, transplanted from a matched donor who had ≥1 MRD measurement prior to and/or 100 days and/or 1 year after HSCT were eligible. A threshold of 0.01% defined MRD positivity versus negativity. Prior to HSCT, 21% of patients were MRDpos. Three-year event-free survival (EFS) was 0.73 and 0.59 (p<0.001), and 3-year cumulative incidence of relapse (CIR) was 0.20 and 0.33 (p<0.001) in MRDneg and MRDpos patients, respectively. The level of MRD positivity pre-HSCT (<0.1% versus ≥0.1%), did not significantly affect outcome. Pre-HSCT MRDneg and TBI/etoposide conditioning were associated with a 2-fold lower risk of relapse, whereas MRDpos had a 2-fold higher risk of any failure and/or death. No detrimental effect of MRDpos pre-HSCT could be demonstrated in patients with T-cell ALL. MRDpos versus MRDneg patients at day 100 had an EFS of 0.47 versus 0.77 (p<0.001) and a CIR of 0.51 versus 0.17 (p<0.001), respectively, but post-HSCT MRDpos did not necessarily imply relapse. In conclusion, the MRD status pre-HSCT and at day 100 post-HSCT was a strong prognostic factor for children transplanted for ALL in the extended FORUM cohort. https://haematologica.org/article/view/12206 |
| spellingShingle | Adriana Balduzzi Evgenia Glogova Christina Peters Petr Sedlacek Jean-Hugues Dalle Franco Locatelli Roland Meisel Birgit Burkhardt Jochen Buechner Jacek Wachowiak Marc Bierings Raquel Staciuk Stelios Graphakos Tayfun Güngör Akif Yesilipek Peter Svec Julia Palma Gergely Krivan Cristina Diaz-de-Heredia Francesca Limido Marc Ansari Krzysztof Kalwak Peter Bader Marianne Ifversen Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM Trial Haematologica |
| title | Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM Trial |
| title_full | Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM Trial |
| title_fullStr | Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM Trial |
| title_full_unstemmed | Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM Trial |
| title_short | Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM Trial |
| title_sort | impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the forum trial |
| url | https://haematologica.org/article/view/12206 |
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