Mitoxantrone, not idarubicin, significantly improves the outcome of children with ALL: result of the international randomised ALLR3 study


Year:

Session type:

Catriona Parker1, Rachel Waters2, Carly Leighton3, Ashish Masurekar1, Nick Goulden4, Anthony Moorman5, Rosemary Sutton6, Tom Revesz7, Phil Ancliff4, Mary Morgan8, Phil Darbyshire9, Vaskar Saha1

1University of Manchester, UK, 2University of Oxford, UK, 3Queen Mary University, UK, 4Great Ormond Street Hospital, London, UK, 5Northern Institute for Cancer Research, Newcastle, UK, 6Children's Cancer Institute Australia for Medical Research, Randwick, Australia, 7Children, Youth and Women's Health Service, Adelaide, Australia, 8Southampton General Hospital, UK, 9Birmingham Children's Hospital, UK

Abstract

Proffered paper presentation

Background
Children who relapse after treatment of Acute Lymphoblastic Leukaemia (ALL) have a poor outcome. The international ALLR3 trial (ISCTRN 45724312) was designed to answer two questions: (1) Benefit of Mitoxantrone over Idarubicin in induction? (2) Is chemotherapy curative for those with Minimal Residual Disease (MRD) <10-4 post-induction?

Methods
Risk stratified randomised study run on an indigenous web-based trial database with automated entry, randomisation and decision support. The study recruited from all centres in the UK, Ireland, Australia and New Zealand. Statistical tests included Kaplan-Meier and Cox regression analysis.

Results
A total of 212 patients were randomised, of whom 103 received Mitoxantrone and 109 Idarubicin. The respective overall survivals (OS) were 67% and 40% (p=0.01). The most significant improvements with Mitoxantrone were seen in the Intermediate Risk (IR) group (OS 78% vs 44%), especially in those transplanted (OS 88% vs 44%). In the Mitoxantrone IR group, the OS for those who received chemotherapy is comparable to those who received a Stem Cell Transplant (p=0.98).

Conclusion

  • Mitoxantrone is highly effective in relapsed ALL.
  • SCT is not necessary in children with relapsed ALL who have a MRD<10-4 after induction.