Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study
| Autor: | Peters, Christina, Dalle, Jean-Hugues, Locatelli, Franco, Poetschger, Ulrike, Sedlacek, Petr, Buechner, Jochen, Shaw, Peter J, Staciuk, Raquel, Ifversen, Marianne, Pichler, Herbert, Vettenranta, Kim, Svec, Peter, Aleinikova, Olga, Stein, Jerry, Güngör, Tayfun, Toporski, Jacek, Truong, Tony H, Diaz-de-Heredia, Cristina, Bierings, Marc, Ariffin, Hany, Essa, Mohammed, Burkhardt, Birgit, Schultz, Kirk, Meisel, Roland, Lankester, Arjan, Ansari Djaberi, Marc Georges, Schrappe, Martin, von Stackelberg, Arend, Balduzzi, Adriana, Corbacioglu, Selim, Bader, Peter, IBFM Study Group, IntReALL Study Group, I-BFM SCT Study Group, EBMT Paediatric Diseases Working Party |
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| Přispěvatelé: | Peters, C, Dalle, J, Locatelli, F, Poetschger, U, Sedlacek, P, Buechner, J, Shaw, P, Staciuk, R, Ifversen, M, Pichler, H, Vettenranta, K, Svec, P, Aleinikova, O, Stein, J, Güngör, T, Toporski, J, Truong, T, Diaz-de-Heredia, C, Bierings, M, Ariffin, H, Essa, M, Burkhardt, B, Schultz, K, Meisel, R, Lankester, A, Ansari, M, Schrappe, M, von Stackelberg, A, Balduzzi, A, Corbacioglu, S, Bader, P, HUS Children and Adolescents, University Management, Lastentautien yksikkö, Children's Hospital |
| Rok vydání: | 2021 |
| Předmět: |
Male
Oncology Cancer Research Lymphoblastic Leukemia medicine.medical_treatment Hematopoietic stem cell transplantation law.invention 0302 clinical medicine Randomized controlled trial 3123 Gynaecology and paediatrics Busulfan / analogs & derivatives law Antineoplastic Combined Chemotherapy Protocols TBI Child Childhood all Etoposide Busulfan / administration & dosage Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy ddc:618 Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology Chemoradiotherapy ORIGINAL REPORTS Precursor Cell Lymphoblastic Leukemia-Lymphoma Total body irradiation Prognosis 3. Good health Survival Rate Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA Child Preschool 030220 oncology & carcinogenesis HSCT hematopoietic stem cell transplantation Chemoradiotherapy / mortality Female Vidarabine Whole-Body Irradiation medicine.medical_specialty Adolescent 3122 Cancers Vidarabine / analogs & derivatives acute lymphoblastic leukemia Equivalence Trials as Topic 03 medical and health sciences Internal medicine Antineoplastic Combined Chemotherapy Protocols / therapeutic use Hematologic Malignancy medicine Humans Busulfan Survival rate childhood Chemotherapy business.industry International Agencies Thiotepa / administration & dosage Clinical trial Etoposide / administration & dosage Vidarabine / administration & dosage Whole-Body Irradiation / mortality business Literatur Kommentiert total body irradiation Thiotepa Follow-Up Studies 030215 immunology |
| Zdroj: | Journal of clinical oncology, Vol. 39, No 4 (2021) pp. 295-307 Journal of Clinical Oncology Journal of Clinical Oncology, 39(4), 295-308. LIPPINCOTT WILLIAMS & WILKINS Strahlentherapie Und Onkologie |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.20.02529 |
| Popis: | 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, in complete 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. |
| Databáze: | OpenAIRE |
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