Peters, Christina and Dalle, Jean-Hugues and Locatelli, Franco and Poetschger, Ulrike and Sedlacek, Petr and Buechner, Jochen and Shaw, Peter J. and Staciuk, Raquel and Ifversen, Marianne and Pichler, Herbert and Vettenranta, Kim and Svec, Peter and Aleinikova, Olga and Stein, Jerry and Gungor, Tayfun and Toporski, Jacek and Truong, Tony H. and Diaz-de-Heredia, Cristina and Bierings, Marc and Ariffin, Hany and Essa, Mohammed and Burkhardt, Birgit and Schultz, Kirk and Meisel, Roland and Lankester, Arjan and Ansari, Marc and Schrappe, Martin and von Stackelberg, Arend and Balduzzi, Adriana and Corbacioglu, Selim and Bader, Peter (2021) Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study. JOURNAL OF CLINICAL ONCOLOGY, 39 (4). 295-+. ISSN 0732-183X, 1527-7755
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PURPOSE Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious, but long-term side effects are concerning. We investigated whether preparative combination chemotherapy could replace TBI in such patients. PATIENTS AND METHODS FORUM is a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study. Patients <= 18 years at diagnosis, 4-21 years at HSCT, incomplete remission pre-HSCT, and with an HLA-compatible related or unrelated donor were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. With 1,000 patients randomly assigned in 5 years, 2-year minimum follow-up, and one-sided alpha of 5%, 80% power was calculated. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI (EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129). RESULTS Between April 2013 and December 2018, 543 patients were screened, 417 were randomly assigned, 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019. The median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI (0.91; 95% CI, 0.86 to 0.95; P<.0001) versus chemoconditioning (0.75; 95% CI, 0.67 to 0.81). Two-year cumulative incidence of relapse and treatment-related mortality were 0.12 (95% CI, 0.08 to 0.17; P<.0001) and 0.02 (95% CI,, 0.01 to 0.05; P = .0269) following TBI and 0.33 (95% CI, 0.25 to 0.40) and 0.09 (95% CI, 0.05 to 0.14) following chemoconditioning, respectively. CONCLUSION Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients. 4 years old with high-risk ALL undergoing allogeneic HSCT. (C) 2020 by American Society of Clinical Oncology
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; LONG-TERM; 2ND REMISSION; INTRAVENOUS BUSULFAN; PEDIATRIC-PATIENTS; CHILDREN; BLOOD; OUTCOMES; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Abteilung für Pädiatrische Hämatologie, Onkologie und Stammzelltransplantation |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Sep 2022 12:55 |
| Last Modified: | 30 Sep 2022 12:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48136 |
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