title: Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  Adults followed and tolerated the NOPHO ALL2008 protocol virtually as well as children, although thrombosis and avascular osteonecrosis was most common among adolescents.
authors: Department of Hematology, Herlev University Hospital, University of Copenhagen, Herlev, Denmark.
authors: Nina
authors: N
authors: Toft
authors: Department of Hematology, Herlev University Hospital, University of Copenhagen, Herlev, Denmark.
authors: Henrik
authors: H
authors: Birgens
authors: Department of Clinical Sciences, Queen Silvia's Children's Hospital, Gothenburg, Sweden.
authors: Jonas
authors: J
authors: Abrahamsson
authors: Hematology, Oncology and Transfusion Medicine Center Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
authors: Laimonas
authors: L
authors: Griškevičius
authors: Department of Hematology, Uppsala University Hospital, Uppsala, Sweden.
authors: Helene
authors: H
authors: Hallböök
authors: Childhood Cancer Research Unit, Karolinska Institute, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors: Mats
authors: M
authors: Heyman
authors: Department of Hematology, Herlev University Hospital, University of Copenhagen, Herlev, Denmark.
authors: Tobias Wirenfeldt
authors: TW
authors: Klausen
authors: Children's Hospital, Landspitali University Hospital, Reykjavík, Iceland.
authors: Ólafur Gísli
authors: ÓG
authors: Jónsson
authors: Department of Hematology, North Estonia Medical Centre, Tallinn, Estonia.
authors: Katrin
authors: K
authors: Palk
authors: Kaie Pruunsild, Tallinn Children's Hospital, Tallinn, Estonia.
authors: Kaie
authors: K
authors: Pruunsild
authors: Department of Hematology, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
authors: Petter
authors: P
authors: Quist-Paulsen
authors: Centre for Pediatric Oncology and Hematology, Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania.
authors: Goda
authors: G
authors: Vaitkeviciene
authors: Division of Hematology-Oncology and Stem Cell Transplantation, Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki, Finland.
authors: Kim
authors: K
authors: Vettenranta
authors: Department of Pediatrics, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
authors: Ann
authors: A
authors: Asberg
authors: Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
authors: Louise Rold
authors: LR
authors: Helt
authors: Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
authors: Thomas
authors: T
authors: Frandsen
authors: Department of Pediatrics and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.|Institute of Gynecology, Obstetrics and Pediatrics, Faculty of Medicine. University of Copenhagen, Copenhagen, Denmark.
authors: Kjeld
authors: K
authors: Schmiegelow
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000633:toxicity; D008875:Middle Aged; D010020:Osteonecrosis / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage / Q000633:toxicity; D011379:Prognosis; D012074:Remission Induction; D013927:Thrombosis / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D014750:Vincristine; D011241:Prednisone; D008727:Methotrexate
keywords: acute lymphoblastic leukemia; adults; children; toxicity; treatment