Toxicity profile and treatment delays in NOPHO ALL2008-comparing adults and children with Philadelphia chromosome-negative acute lymphoblastic leukemia

Eur J Haematol. 2016 Feb;96(2):160-9. doi: 10.1111/ejh.12562. Epub 2015 Apr 24.

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.

Keywords: acute lymphoblastic leukemia; adults; children; toxicity; treatment.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Male
  • Methotrexate / administration & dosage
  • Methotrexate / toxicity
  • Middle Aged
  • Osteonecrosis / chemically induced
  • Osteonecrosis / diagnosis*
  • Osteonecrosis / genetics
  • Osteonecrosis / pathology
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Prednisone / administration & dosage
  • Prednisone / toxicity
  • Prognosis
  • Remission Induction
  • Thrombosis / chemically induced
  • Thrombosis / diagnosis*
  • Thrombosis / genetics
  • Thrombosis / pathology
  • Treatment Outcome
  • Vincristine / administration & dosage
  • Vincristine / toxicity

Substances

  • Vincristine
  • Prednisone
  • Methotrexate