Outcomes of BCP-ALL with hypodiploidy or <i>BCR</i> :: <i>ABL1</i> fusion in children undergoing allogeneic HSCT: results from the FORUM study
Abstract
Abstract Hypodiploid and BCR::ABL1+ B-cell precursor acute lymphoblastic leukemia (BCP-ALL) confers a high risk of disease relapse. We investigated post–hematopoietic stem cell transplantation (HSCT) outcomes within the prospective FORUM trial, comparing outcomes among these genetic subgroups with those of patients without these lesions. The use of pre- and post-HSCT add-on treatments, including tyrosine kinase inhibitors (TKI) and immunotherapies, was also assessed. Multivariate analysis evaluated associations with overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR). The FORUM trial enrolled 741 patients aged ≥4 years with BCP-ALL who underwent HSCT from HLA-matched donors (2013-2023). The 3-year OS and EFS did not differ significantly between patients with BCR::ABL1 fusion, hypodiploidy, and neither of these 2 genetic lesions. However, patients with hypodiploid BCP-ALL in second complete remission (CR2) showed inferior OS and EFS, driven by higher nonrelapse mortality (NRM), which occurred exclusively in near-diploid cases. No NRM occurred in severe hypodiploid cases conditioned with total body irradiation. Minimal residual disease (MRD) positivity at transplant predicted worse OS, EFS, and CIR in all genetic groups. Patients with hypodiploid BCP-ALL were difficult to salvage after relapse, even with chimeric antigen receptor T-cell therapy. By contrast, BCR::ABL1+ patients had favorable outcomes, even when MRD positive before HSCT. Prophylactic TKI use after HSCT improved EFS and reduced CIR. BCR::ABL1+ patients who received a transplant in CR2 had a 3-year OS of 96%. In conclusion, the standardized FORUM protocol yielded comparable outcomes across genetic subgroups. Posttransplant TKI maintenance improved outcomes in BCR::ABL1+ BCP-ALL. This trial was registered at www.clinicaltrials.gov as #NCT01949129 and at www.clinicaltrialsregister.eu as #EudraCT2012-0032-22.
Article Details
Authors (26)
Jochen Buechner
1Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway
Ulrike Poetschger
2St. Anna Children's Cancer Research Institute, Vienna, Austria
Peter Bader
3Division for Stem Cell Transplantation, Immunology, Department of Pediatrics, Goethe University, University Hospital, Frankfurt am Main, Germany
Akif Yeşilipek
4Pediatric Stem Cell Transplantation Unit, Antalya Medical Park Hospital, Antalya, Turkey
Herbert Pichler
2St. Anna Children's Cancer Research Institute, Vienna, Austria
Julia Palma
6Department of Pediatrics–Bone Marrow Transplantation Unit, Faculty of Medicine, Hospital Luis Calvo Mackenna, University of Chile, Santiago, Chile
Raquel Staciuk
7Hospital de Pediatría Prof. Dr. Juan P. Garrahan, Buenos Aires, Argentina
Petr Riha
9Department of Pediatric Hematology and Oncology, Motol University Hospital, Prague, Czech Republic
Gergely Kriván
10Pediatric Hematology and Stem Cell Transplantation Department, Central Hospital of Southern Pest, National Institute of Hematology and Infectious Diseases, Budapest, Hungary
Marianne Ifversen
11Department of Pediatric and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Tayfun Güngör
12Department of Hematology/Oncology/Immunology, Gene Therapy, and Stem Cell Transplantation, Eleonore Foundation and Children’s Research Center, University Children’s Hospital, Zürich, Switzerland
Evgenios Goussetis
13Stem Cell Transplant Unit, Agia Sofia Children's Hospital, Athens, Greece
Krzysztof Kalwak
14Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Wroclaw, Poland
Jacek Toporski
15Department Cell Therapy and Allogeneic Stem Cell Transplant, Karolinska University Hospital, Stockholm, Sweden
Melissa Gabriel
16The Children's Hospital at Westmead, Sydney, Australia
Marleen Renard
17University Hospital Leuven, Leuven, Belgium
Cristina Diaz-de-Heredia
18Department of Pediatric Hematology and Oncology, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca, Barcelona, Spain
Toni Matic
19Department of Pediatrics, University Hospital Center Zagreb, Zagreb, Croatia
Friso G. Calkoen
Peter Švec
Institute of Physics, Slovak Academy of Sciences, Dúbravská cesta 9, SK-845 11 Bratislava, Slovakia
Roland Meisel
Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
Adriana Balduzzi
23Pediatric Hematopoietic Transplant Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
Franco Locatelli
IRCCS Ospedale Pediatrico Bambino Gesù Rome, Rome
Christina Peters
2St. Anna Children's Cancer Research Institute, Vienna, Austria
Jean-Hugues Dalle
27Hemato-Immunology Department, Robert Debré Academic Hospital, GHU AP-HP Nord Université Paris Cité, Paris, France
Jerry Stein
28Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel