Impact of Minimal Residual Disease on the Outcome of Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia within the FORUM trial

Sep 29, 2026

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In the randomized international phase-III FORUM trial, outcomes in pediatric acute lymphoblastic leukemia after hematopoietic stem cell transplantation (HSCT) were linked to conditioning strategy and remission phase, while pre-HSCT MRD was not previously decisive. This extended cohort evaluates MRD impact using 1,014 children aged 4–21. MRD positivity was defined by a 0.01% threshold. MRD status pre-HSCT and at day 100 strongly predicted event-free survival and relapse, including higher failure or death risk for MRDpos before and after HSCT.

LanguageEnglish

CategoryResearch & Report

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Pages13

Reading Time33 min

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Abstract

Introduction

ARTICLE-Acute Lymphoblastic Leukemia Impact of minimal residual disease on the outcome of hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia within the FORUM trial Adriana Balduzzi,1,2 Evgenia Glogova,3 Christina Peters,3,4 Petr Sedlacek,5 Jean-Hugues Dalle,6,7 Franco Locatelli,8,9 Roland Meisel,10 Birgit Burkhardt,11 Jochen Buechner,12 Jacek Wachowiak,13 Marc Bierings,14,15 Raquel Staciuk,16 Stelios Graphakos,17 Tayfun Güngör,18 Akif Yesilipek,19 Peter Svec,20 Julia Palma,21 Gergely Krivan,22 Cristina Diaz-de-Heredia,23 Francesca Limido,2 Marc Ansari,24,25 Krzysztof Kalwak,26 Peter Bader27\# and Marianne Ifversen28\# 1 Pediatric Department, Fondazione IRCCS San Gerardo, Monza, Italy; 2School of Medicine and Surgery, Milano-Bicocca University, Monza, Italy; 3St. Anna Children’s Cancer Research Institute, Vienna, Austria; 4St. Anna Children’s Hospital, Medical University Vienna, Vienna, Austria; 5 Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czech Republic; 6 Hemato-Immunology Department, Robert-Debré Hospital, GHUAP-HP Nord, Paris, France; 7 Université Paris Cité, Paris, France; 8 Department of Pediatric Hematology and Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Ospedale Pediatrico Bambino Gesù, Roma, Italy; 9Catholic University of the Sacred Heart, Rome, Italy; 10 Department of Pediatric Oncology, Hematology and Clinical Immunology, Division of Pediatric Stem Cell Therapy, Medical Faculty, Heinrich Heine University, Duesseldorf, Germany; 11 Department of Pediatric Hematology and Oncology, University Children’s Hospital Muenster, Muenster, Germany; 12 Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway; 13 Department of Pediatric Oncology, Hematology and Transplantology, University of Medical Sciences, Poznań, Poland; 14 Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; 15 Utrecht University Children’s Hospital, Utrecht, the Netherlands; 16 Hospital de Pediatría “Prof. Dr. Juan P. Garrahan,” Buenos Aires, and Hospital Sor Maria Ludovica, La Plata, Buenos Aires, Argentina; 17Aghia Sophia Children’s University Hospital, Athens, Greece; 18 Eleonore Foundation & Children’s Research Center, Zürich, Switzerland; 19 Pediatric Stem Cell Transplantation Unit, Antalya Medical Park Hospital, Antalya, Turkey; 20 Department of Pediatric Hematology and Oncology, National Institute of Children’s Diseases, Comenius University, Bratislava, Slovakia; 21 Faculty of Medicine, Hospital Luis Calvo Mackenna, Department of Pediatrics-Bone Marrow Transplantation Unit, University of Chile, Santiago, Chile; 22 Pediatric Hematology and Stem Cell Transplantation Department, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary; 23 Division of Pediatric Hematology and Oncology, University Hospital Vall d’Hebron, Barcelona, Spain; 24CANSEARCH Research Platform for Pediatric Oncology and Hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland; 25 Department of Women, Child and Adolescent, Division of Pediatric Oncology and Hematology, University Geneva Hospitals, Geneva, Switzerland; 26 Department of Pediatric Hematology/Oncology and BMT, Wroclaw Medical University, Wroclaw, Poland; 27 Department of Pediatrics, Division for Stem Cell Transplantation, Immunology, Goethe University, University Hospital Frankfurt am Main, Frankfurt am Main, Germany and 28 Department of Pediatric and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark \#PB and MI contributed equally as senior authors. Correspondence: A. Balduzzi [adriana.balduzzi@unimib.it](adriana.balduzzi@unimib.it) Received: January 25, 2025. Accepted: July 30, 2025. Early view: August 7, 2025. [https://doi.org/10.3324/haematol.2025.287456](https://doi.org/10.3324/haem

FAQs

How was MRD positivity defined in the extended FORUM cohort?

MRD positivity was defined using a threshold of 0.01% to distinguish MRDpos from MRDneg.

What was the effect of pre-HSCT MRD status on survival and relapse?

Patients who were MRDpos before HSCT had worse outcomes, with lower three-year event-free survival and higher three-year cumulative incidence of relapse compared with MRDneg patients.

Did MRD status at day 100 after HSCT predict outcomes?

Yes. MRDpos at day 100 after HSCT showed substantially lower event-free survival and higher cumulative incidence of relapse than MRDneg, while post-HSCT MRDpos did not necessarily guarantee relapse.

Sep 29, 2026

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