David T Teachey1, Meenakshi Devidas2, Brent L Wood3, Zhiguo Chen4, Robert J Hayashi5, Michelle L Hermiston6, Robert D Annett7, J Hunter Archer4, Barbara L Asselin8, Keith J August9, Steve Y Cho10, Kimberly P Dunsmore11, Brian T Fisher1, Jason L Freedman1, Paul J Galardy12, Paul Harker-Murray13, Terzah M Horton14, Alok I Jaju15, Allison Lam16, Yoav H Messinger17, Rodney R Miles18, Maki Okada16, Samir I Patel19, Eric S Schafer14, Tal Schechter20, Neelam Singh21, Amii C Steele22, Maria Luisa Sulis23, Sarah L Vargas24, Stuart S Winter25, Charlotte Wood4, Patrick Zweidler-McKay26, Catherine M Bollard27, Mignon L Loh6, Stephen P Hunger1, Elizabeth A Raetz28. 1. Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia and The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, PA. 2. Department of Global Pediatric Medicine, St Jude Children's Research Hospital, Memphis, TN. 3. Department of Laboratory Medicine, University of Washington, Seattle, WA. 4. Department of Biostatistics, University of Florida, Gainesville, FL. 5. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St Louis Children's Hospital, St Louis, MO. 6. Department of Pediatrics, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA. 7. Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, NM. 8. Department of Pediatrics and Wilmot Cancer Institute at URMC, University of Rochester School of Medicine and Dentistry, Rochester, NY. 9. Children's Mercy Hospital, Kansas City, MO. 10. University of Wisconsin-Madison and the University of Wisconsin Carbone Cancer Center, Madison, WI. 11. University of Virginia Children's Hospital, Charlottesville, VA. 12. Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN. 13. Children's Wisconsin, Milwaukee, WI. 14. Texas Children's Hospital, Baylor College of Medicine, Houston, TX. 15. Lurie Children's Hospital, Chicago, IL. 16. Miller Children's and Women's Hospital, Long Beach, CA. 17. Children's Hospitals and Clinics, Minneapolis, MN. 18. Department of Pathology and ARUP Institute for Clinical & Experimental Pathology, University of Utah, Salt Lake City, UT. 19. Division of Radiation Oncology, Department of Oncology, University of Alberta, Stollery Children's Hospital, Edmonton, AB, Canada. 20. Haematology/Oncology, Child Health Evaluative Services (CHES) Program Research Institute, The Hospital for Sick Children, Toronto, Canada. 21. Michigan State University Clinical Center, Lansing, MI. 22. Carolinas Medical Center/Levine Cancer Institute, Charlotte, NC. 23. Department of Pediatric Oncology, Memorial Sloan Kettering Cancer Center, New York, NY. 24. Children's Oncology Group, Monrovia, CA. 25. Children's Minnesota Research Institute, Children's Minnesota Research Institute and Cancer and Blood Disorders Program, Minneapolis, MN. 26. ImmunoGen, Inc, Waltham, MA. 27. Children's National Medical Center, Washington, DC. 28. Division of Pediatric Hematology and Oncology, Department of Pediatrics, New York University Langone Health, New York, NY.
Abstract
PURPOSE: To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS: Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS: AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS (P = .412) and OS (P = .600). CONCLUSION: Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.
PURPOSE: To improve the outcomes of patients with T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL), the proteasome inhibitor bortezomib was examined in the Children's Oncology Group phase III clinical trial AALL1231, which also attempted to reduce the use of prophylactic cranial radiation (CRT) in newly diagnosed T-ALL. PATIENTS AND METHODS: Children and young adults with T-ALL/T-LL were randomly assigned to a modified augmented Berlin-Frankfurt-Münster chemotherapy regimen with/without bortezomib during induction and delayed intensification. Multiple modifications were made to the augmented Berlin-Frankfurt-Münster backbone used in the predecessor trial, AALL0434, including using dexamethasone instead of prednisone and adding two extra doses of pegaspargase in an attempt to eliminate CRT in most patients. RESULTS: AALL1231 accrued 824 eligible and evaluable patients from 2014 to 2017. The 4-year event-free survival (EFS) and overall survival (OS) for arm A (no bortezomib) versus arm B (bortezomib) were 80.1% ± 2.3% versus 83.8% ± 2.1% (EFS, P = .131) and 85.7% ± 2.0% versus 88.3% ± 1.8% (OS, P = .085). Patients with T-LL had improved EFS and OS with bortezomib: 4-year EFS (76.5% ± 5.1% v 86.4% ± 4.0%; P = .041); and 4-year OS (78.3% ± 4.9% v 89.5% ± 3.6%; P = .009). No excess toxicity was seen with bortezomib. In AALL0434, 90.8% of patients with T-ALL received CRT. In AALL1231, 9.5% of patients were scheduled to receive CRT. Evaluation of comparable AALL0434 patients who received CRT and AALL1231 patients who did not receive CRT demonstrated no statistical differences in EFS (P = .412) and OS (P = .600). CONCLUSION: Patients with T-LL had significantly improved EFS and OS with bortezomib on the AALL1231 backbone. Systemic therapy intensification allowed elimination of CRT in more than 90% of patients with T-ALL without excess relapse.
Authors: Martin Schrappe; Maria Grazia Valsecchi; Claus R Bartram; André Schrauder; Renate Panzer-Grümayer; Anja Möricke; Rosanna Parasole; Martin Zimmermann; Michael Dworzak; Barbara Buldini; Alfred Reiter; Giuseppe Basso; Thomas Klingebiel; Chiara Messina; Richard Ratei; Giovanni Cazzaniga; Rolf Koehler; Franco Locatelli; Beat W Schäfer; Maurizio Aricò; Karl Welte; Jacques J M van Dongen; Helmut Gadner; Andrea Biondi; Valentino Conter Journal: Blood Date: 2011-06-30 Impact factor: 22.113
Authors: Ching-Hon Pui; Jun J Yang; Stephen P Hunger; Rob Pieters; Martin Schrappe; Andrea Biondi; Ajay Vora; André Baruchel; Lewis B Silverman; Kjeld Schmiegelow; Gabriele Escherich; Keizo Horibe; Yves C M Benoit; Shai Izraeli; Allen Eng Juh Yeoh; Der-Cherng Liang; James R Downing; William E Evans; Mary V Relling; Charles G Mullighan Journal: J Clin Oncol Date: 2015-08-24 Impact factor: 44.544
Authors: Kimberly P Dunsmore; Stuart S Winter; Meenakshi Devidas; Brent L Wood; Natia Esiashvili; Zhiguo Chen; Nancy Eisenberg; Nikki Briegel; Robert J Hayashi; Julie M Gastier-Foster; Andrew J Carroll; Nyla A Heerema; Barbara L Asselin; Karen R Rabin; Patrick A Zweidler-Mckay; Elizabeth A Raetz; Mignon L Loh; Kirk R Schultz; Naomi J Winick; William L Carroll; Stephen P Hunger Journal: J Clin Oncol Date: 2020-08-19 Impact factor: 44.544
Authors: Martin Schrappe; Stephen P Hunger; Ching-Hon Pui; Vaskar Saha; Paul S Gaynon; André Baruchel; Valentino Conter; Jacques Otten; Akira Ohara; Anne Birgitta Versluys; Gabriele Escherich; Mats Heyman; Lewis B Silverman; Keizo Horibe; Georg Mann; Bruce M Camitta; Jochen Harbott; Hansjörg Riehm; Sue Richards; Meenakshi Devidas; Martin Zimmermann Journal: N Engl J Med Date: 2012-04-12 Impact factor: 91.245
Authors: L B Silverman; K E Stevenson; J E O'Brien; B L Asselin; R D Barr; L Clavell; P D Cole; K M Kelly; C Laverdiere; B Michon; M A Schorin; C L Schwartz; E W O'Holleran; D S Neuberg; H J Cohen; S E Sallan Journal: Leukemia Date: 2009-12-17 Impact factor: 11.528
Authors: R Peto; M C Pike; P Armitage; N E Breslow; D R Cox; S V Howard; N Mantel; K McPherson; J Peto; P G Smith Journal: Br J Cancer Date: 1977-01 Impact factor: 7.640