Safety assessment of intensive induction therapy in childhood anaplastic large cell lymphoma: report of the ALCL99 randomised trial

Pediatr Blood Cancer. 2011 Jul 1;56(7):1071-7. doi: 10.1002/pbc.22940. Epub 2011 Jan 28.

Abstract

Background: ALCL99 protocol including six courses of chemotherapy derived from the NHL-BFM protocol is widely used for the treatment of paediatric anaplastic large-cell lymphoma. In the ALCL99 trial, patients were randomised to receive MTX 1 g/m² in 24 hr with intrathecal injection (MTX1) versus MTX 3 g/m² in 3 hr without intrathecal (MTX3); then to receive or not vinblastine (high-risk patients). The present study provides information about the acute adverse reactions (ARs) during the six courses of the ALCL99 treatment, assesses risk factors for ARs and evaluates the risk of overweight related to treatment.

Methods: Data concerning ARs were assessed using CTCv2 and analysed overall and according to the type of course.

Results: Between 1999 and 2005, 352 patients were recruited. Toxicity assessed after 2050 courses included grade 4 neutropaenia (70% of courses), grade 3-4 stomatitis (13%), grade 3-4 transaminase elevation (10%) and grade 3-4 infection (5%). Four patients (1%) died of toxicity. The toxicity profile differed between courses-A (significantly more haematological toxicity) and courses-B (significantly more stomatitis). The percentage of ARs was higher after the first course than after subsequent courses. Severe toxicity was more frequent after MTX1 than after MTX3 courses but did not differ between courses with or without vinblastine. Overall 20% of patients had a weight gain exceeding 20%.

Conclusions: The high rate of acute toxicity should be considered when using the ALCL99 protocol. Chemotherapy including MTX 3 g/m² in 3 hr was less toxic than the same regimen with MTX 1 g/m² in 24 hr. Adding vinblastine did not increase the risk of toxicity.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Injections, Spinal
  • Lymphoma, Large-Cell, Anaplastic / drug therapy*
  • Male
  • Methotrexate / administration & dosage
  • Risk Assessment
  • Risk Factors
  • Survival Rate
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Young Adult

Substances

  • Vinblastine
  • Methotrexate