Incidence of subsequent malignancies after total body irradiation-based allogeneic HSCT in children with ALL - long-term follow-up from the prospective ALL-SCT 2003 trial.

Humans Child Whole-Body Irradiation / adverse effects Graft vs Host Disease / epidemiology Transplantation Conditioning / adverse effects Incidence Follow-Up Studies Transplantation, Homologous / adverse effects Etoposide Prospective Studies Hematopoietic Stem Cell Transplantation / adverse effects Busulfan Cyclophosphamide Neoplasms / complications

Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
11 2022
Historique:
received: 20 07 2022
accepted: 26 08 2022
revised: 25 08 2022
pubmed: 14 9 2022
medline: 1 11 2022
entrez: 13 9 2022
Statut: ppublish

Résumé

Total body irradiation (TBI)-based conditioning is associated with superior leukemia-free survival in children with ALL undergoing HSCT. However, the risk for subsequent malignant neoplasms (SMN) remains a significant concern. We analyzed 705 pediatric patients enrolled in the prospective ALL-SCT-BFM-2003 trial and its subsequent registry. Patients >2 years received conditioning with TBI 12 Gy/etoposide (n = 558) and children ≤2 years of age or with contraindications for TBI received busulfan/cyclophosphamide/etoposide (n = 110). The 5- and 10-year cumulative incidence of SMN was 0.02 ± 0.01 and 0.13 ± 0.03, respectively. In total, 39 SMN (34 solid tumors, 5 MDS/AML) were diagnosed in 33 patients at a median of 5.8 years (1.7-13.4), exclusively in the TBI group. Of 33 affected patients, 21 (64%) are alive at a median follow-up of 5.1 years (0-9.9) after diagnosis of their first SMN. In univariate analysis, neither age at HSCT, donor type, acute GVHD, chronic GVHD, nor CMV constituted a significant risk factor for SMN. The only significant risk factor was TBI versus non-TBI based conditioning. This analysis confirms and quantifies the increased risk of SMN in children with ALL after conditioning with TBI. Future strategies to avoid TBI will need careful tailoring within prospective, controlled studies to prevent unfavorable outcomes.

Identifiants

DOI: 10.1038/s41375-022-01693-z PMID: 36097283 PMC: PMC9613465
pubmed: 36097283
doi: 10.1038/s41375-022-01693-z
pii: 10.1038/s41375-022-01693-z
pmc: PMC9613465
doi:

Substances chimiques

Etoposide 6PLQ3CP4P3
Busulfan G1LN9045DK
Cyclophosphamide 8N3DW7272P

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2567-2576

Informations de copyright

© 2022. The Author(s).

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Auteurs

Anna Eichinger (A)

Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU, Munich, Germany.
ORCID: 0000-0002-2256-6633

Ulrike Poetschger (U)

Children's Cancer Research Institute, Vienna, Austria.

Evgenia Glogova (E)

Children's Cancer Research Institute, Vienna, Austria.

Peter Bader (P)

Division for Stem Cell Transplantation and Immunology, Department for Children and Adolescents, University Hospital, Goethe University, Frankfurt/Main, Germany.
ORCID: 0000-0003-4554-0265

Oliver Basu (O)

Department of Pediatrics III, University Hospital Essen, University Medicine Essen, Essen, Germany.

Rita Beier (R)

Department of Pediatric Oncology and Hematology, Medizinische Hochschule Hannover, Hannover, Germany.

Birgit Burkhardt (B)

Pediatric Hematology and Oncology, University Hospital Muenster, Muenster, Germany.
ORCID: 0000-0002-1151-829X

Carl-Friedrich Classen (CF)

Oncology and Hematology Unit, Children's Hospital, University Medicine Rostock, Rostock, Germany.

Alexander Claviez (A)

Department of Pediatrics and Bone Marrow Transplant Unit, Medical University of Schleswig-Holstein, Campus Kiel, Kiel, Germany.
ORCID: 0000-0001-7064-8556

Selim Corbacioglu (S)

Department of Pediatric Hematology, Oncology and Stem Cell Transplantation, University of Regensburg, Regensburg, Germany.

Hedwig E Deubzer (HE)

Department of Pediatric Hematology and Oncology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität Berlin, Berlin, Germany.
Experimental and Clinical Research Center (ECRC) of the Charité and the Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, Berlin, Germany.
ORCID: 0000-0002-6115-4893

Johann Greil (J)

Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany.

Bernd Gruhn (B)

Department of Pediatrics, Jena University Hospital, Jena, Germany.
ORCID: 0000-0003-1862-0075

Tayfun Güngör (T)

Department of Hematology/Oncology/Immunology, Gene-therapy, and Stem Cell Transplantation, University Children's Hospital Zurich - Eleonore Foundation & Children's Research Center (CRC), Zurich, Switzerland.
ORCID: 0000-0002-3261-1186

Kinan Kafa (K)

Department of Pediatrics, University of Halle, Halle, Germany.

Jörn-Sven Kühl (JS)

Department of Pediatric Oncology, Hematology and Hemostaseology, University of Leipzig, Leipzig, Germany.

Peter Lang (P)

University Children's Hospital, Tübingen, Germany.
ORCID: 0000-0001-7737-2142

Bjoern Soenke Lange (BS)

Department of Pediatrics, University Hospital Carl Gustav Carus, Technical University of Dresden, Dresden, Germany.

Roland Meisel (R)

Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
ORCID: 0000-0001-5230-0628

Ingo Müller (I)

Divison of Pediatric Stem Cell Transplantation and Immunology, Clinic for Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
ORCID: 0000-0002-7477-6632

Martin G Sauer (MG)

Department of Pediatric Oncology and Hematology, Medizinische Hochschule Hannover, Hannover, Germany.

Paul-Gerhardt Schlegel (PG)

Department of Pediatric Hematology and Oncology, University Children's Hospital Würzburg, Würzburg, Germany.

Ansgar Schulz (A)

Department of Pediatrics, University Medical Center Ulm, Ulm, Germany.
ORCID: 0000-0002-7798-7996

Daniel Stachel (D)

Children's Hospital, Universitätsklinikum Erlangen, Erlangen, Germany.

Brigitte Strahm (B)

Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0002-6086-130X

Angela Wawer (A)

Department of Pediatrics and Children's Cancer Research Center, Kinderklinik München Schwabing, Technical University of Munich School for Medicine, Munich, Germany.

Christina Peters (C)

St. Anna Children's Hospital, University Vienna, St. Anna Children's Cancer Research Institute, Vienna, Austria.
ORCID: 0000-0003-0369-8515

Michael H Albert (MH)

Department of Pediatrics, Dr. von Hauner Children's Hospital, University Hospital, LMU, Munich, Germany. michael.albert@med.lmu.de.
ORCID: 0000-0001-9143-3263

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Incidence of subsequent malignancies after...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Incidence of subsequent malignancies after...
questionsmedicales.fr › Techniques d'investigation › Irradiation corporelle totale › Incidence of subsequent malignancies after...
questionsmedicales.fr › Maladies du système immunitaire › Maladie du greffon contre l'hôte › Incidence of subsequent malignancies after...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunosuppression thérapeutique › Conditionnement pour greffe › Incidence of subsequent malignancies after...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Morbidité › Incidence › Incidence of subsequent malignancies after...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études de suivi › Incidence of subsequent malignancies after...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation homologue › Incidence of subsequent malignancies after...
questionsmedicales.fr › Glucides › Hétérosides › Glucosides › Étoposide › Incidence of subsequent malignancies after...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Incidence of subsequent malignancies after...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches hématopoïétiques › Incidence of subsequent malignancies after...
questionsmedicales.fr › Composés chimiques organiques › Composés du soufre › Acides du soufre › Acides sulfoniques › Acides alcanesulfoniques › Alcanesulfonates › Méthanesulfonates › Busulfan › Incidence of subsequent malignancies after...
questionsmedicales.fr › Composés chimiques organiques › Composés organiques du phosphore › Phosphoramides › Moutardes phosphoramide › Cyclophosphamide › Incidence of subsequent malignancies after...
questionsmedicales.fr › Tumeurs › Incidence of subsequent malignancies after...