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