Nina Toft1, Henrik Birgens1, Jonas Abrahamsson2, Laimonas Griškevičius3, Helene Hallböök4, Mats Heyman5, Tobias Wirenfeldt Klausen1, Ólafur Gísli Jónsson6, Katrin Palk7, Kaie Pruunsild8, Petter Quist-Paulsen9, Goda Vaitkeviciene10, Kim Vettenranta11, Ann Asberg12, Louise Rold Helt13, Thomas Frandsen13, Kjeld Schmiegelow13,14. 1. Department of Hematology, Herlev University Hospital, University of Copenhagen, Herlev, Denmark. 2. Department of Clinical Sciences, Queen Silvia's Children's Hospital, Gothenburg, Sweden. 3. Hematology, Oncology and Transfusion Medicine Center Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania. 4. Department of Hematology, Uppsala University Hospital, Uppsala, Sweden. 5. Childhood Cancer Research Unit, Karolinska Institute, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 6. Children's Hospital, Landspitali University Hospital, Reykjavík, Iceland. 7. Department of Hematology, North Estonia Medical Centre, Tallinn, Estonia. 8. Kaie Pruunsild, Tallinn Children's Hospital, Tallinn, Estonia. 9. Department of Hematology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. 10. Centre for Pediatric Oncology and Hematology, Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania. 11. Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland. 12. Department of Pediatrics, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway. 13. Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark. 14. Institute of Gynecology, Obstetrics and Pediatrics, Faculty of Medicine. University of Copenhagen, Copenhagen, Denmark.
Abstract
OBJECTIVES: Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults. METHODS: We collected information on 19 treatment-related toxicities, systematically captured at 3-month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1-45 yrs treated according to the Nordic/Baltic ALL2008 protocol. RESULTS: No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18-45 yrs being significantly delayed during two of nine high-risk blocks (median number of days for patients 1-9, 10-17, and 18-45 yrs; the glucocorticosteroid/antimetabolite-based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15-17 yrs compared with children 1-9 yrs (P < 0.0001). Risk of avascular osteonecrosis was related to age with the highest OR for patients 10-14 yrs (OR = 10.4 (95% CI: (4.4;24.9)), P < 0.0001). CONCLUSION: Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents.
OBJECTIVES: Cure rates improve when adolescents and young adults with acute lymphoblastic leukemia (ALL) are treated according to pediatric protocols. Assumed risks of toxicities and associated delays in treatment have played a role in setting upper age limits. The aim of this study was to examine the toxicity profile and treatment delays in NOPHO ALL2008 comparing children and adults. METHODS: We collected information on 19 treatment-related toxicities, systematically captured at 3-month intervals throughout therapy, and time intervals between 12 consecutive treatment phases for 1076 patients aged 1-45 yrs treated according to the Nordic/Baltic ALL2008 protocol. RESULTS: No adults died during induction. The duration of induction therapy and postinduction treatment phases did not differ between children and adults, except for patients 18-45 yrs being significantly delayed during two of nine high-risk blocks (median number of days for patients 1-9, 10-17, and 18-45 yrs; the glucocorticosteroid/antimetabolite-based block B1: 24, 26, and 29 d, respectively, P = 0.001, and Block 5 (in most cases also a B block): 29, 29, and 37 d, respectively, P = 0.02). A higher incidence of thrombosis with increasing age was found; highest odds ratio 5.4 (95% CI: (2.6;11.0)) for patients 15-17 yrs compared with children 1-9 yrs (P < 0.0001). Risk of avascular osteonecrosis was related to age with the highest OR for patients 10-14 yrs (OR = 10.4 (95% CI: (4.4;24.9)), P < 0.0001). CONCLUSION: Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents.
Authors: N Toft; H Birgens; J Abrahamsson; L Griškevičius; H Hallböök; M Heyman; T W Klausen; Ó G Jónsson; K Palk; K Pruunsild; P Quist-Paulsen; G Vaitkeviciene; K Vettenranta; A Åsberg; T L Frandsen; H V Marquart; H O Madsen; U Norén-Nyström; K Schmiegelow Journal: Leukemia Date: 2017-08-18 Impact factor: 11.528
Authors: Seth E Karol; Leonard A Mattano; Wenjian Yang; Kelly W Maloney; Colton Smith; ChengCheng Liu; Laura B Ramsey; Christian A Fernandez; Tamara Y Chang; Geoffrey Neale; Cheng Cheng; Elaine Mardis; Robert Fulton; Paul Scheet; F Anthony San Lucas; Eric C Larsen; Mignon L Loh; Elizabeth A Raetz; Stephen P Hunger; Meenakshi Devidas; Mary V Relling Journal: Blood Date: 2015-11-20 Impact factor: 22.113