Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): an open-label randomised trial

Cancer Research UK Children's Cancer Group, School of Cancer and Enabling Sciences, University of Manchester, Manchester Academic Health Science Centre, Central Manchester University Hospitals Foundation Trust, Manchester, UK.
The Lancet (Impact Factor: 39.21). 12/2010; 376(9757):2009-17. DOI: 10.1016/S0140-6736(10)62002-8
Source: PubMed

ABSTRACT Although survival of children with acute lymphoblastic leukaemia has improved greatly in the past two decades, the outcome of those who relapse has remained static. We investigated the outcome of children with acute lymphoblastic leukaemia who relapsed on present therapeutic regimens.
This open-label randomised trial was undertaken in 22 centres in the UK and Ireland and nine in Australia and New Zealand. Patients aged 1-18 years with first relapse of acute lymphoblastic leukaemia were stratified into high-risk, intermediate-risk, and standard-risk groups on the basis of duration of first complete remission, site of relapse, and immunophenotype. All patients were allocated to receive either idarubicin or mitoxantrone in induction by stratified concealed randomisation. Neither patients nor those giving interventions were masked. After three blocks of therapy, all high-risk group patients and those from the intermediate group with postinduction high minimal residual disease (≥10(-4) cells) received an allogenic stem-cell transplant. Standard-risk and intermediate-risk patients with postinduction low minimal residual disease (<10(-4) cells) continued chemotherapy. The primary outcome was progression-free survival and the method of analysis was intention-to-treat. Randomisation was stopped in December, 2007 because of differences in progression-free and overall survival between the two groups. This trial is registered, reference number ISCRTN45724312.
Of 239 registered patients, 216 were randomly assigned to either idarubicin (109 analysed) or mitoxantrone (103 analysed). Estimated 3-year progression-free survival was 35·9% (95% CI 25·9-45·9) in the idarubicin group versus 64·6% (54·2-73·2) in the mitoxantrone group (p=0·0004), and 3-year overall survival was 45·2% (34·5-55·3) versus 69·0% (58·5-77·3; p=0·004). Differences in progression-free survival between groups were mainly related to a decrease in disease events (progression, second relapse, disease-related deaths; HR 0·56, 0·34-0·92, p=0·007) rather than an increase in adverse treatment effects (treatment death, second malignancy; HR 0·52, 0·24-1·11, p=0·11).
As compared with idarubicin, mitoxantrone conferred a significant benefit in progression-free and overall survival in children with relapsed acute lymphobastic leukaemia, a potentially useful clinical finding that warrants further investigation.
Cancer Research UK, Leukaemia and Lymphoma Research, Cancer Council NSW, and Sporting Chance Cancer Foundation.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute lymphoblastic leukemia (ALL) is the most common pediatric oncologic diagnosis, and advances in its treatment have led to progressive improvements in survival. The 4 main components of therapy are remission induction, consolidation, maintenance, and central nervous system-directed therapy, and usually last 2 to 3 years. Treatment intensity based on risk-based stratification is the cornerstone of treatment. Patients with features of more favorable disease are spared the more toxic effects of chemotherapy, whereas more aggressive regimens are reserved for those with higher-risk disease. Prognosis of relapsed pediatric ALL depends primarily on duration of remission and site of relapse. Copyright © 2015 Elsevier Inc. All rights reserved.
    Pediatric Clinics of North America 02/2015; 62(1):61-73. DOI:10.1016/j.pcl.2014.09.006 · 2.20 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Relapse period is strongly associated with second relapse risk in relapsed acute lymphoblastic leukemia (ALL) in children. In this context, the treatment outcome of very late relapse should be better; however, data regarding very late relapse is limited. We retrospectively analyzed the outcomes of two consecutive Tokyo Children's Cancer Study Group (TCCSG) ALL trials (1995-2004) with a focus on late relapse, which was divided into two categories: late relapse (6-24 months from the end of therapy, n = 48) and very late relapse (>24 months from the end of therapy, n = 57). Forty-three patients (29 late relapse and 14 very late relapse) received allogeneic hematopoietic stem cell transplantation (HSCT) at second remission. The event-free survival (EFS) probabilities of late relapse and very late relapse were 54.5 ± 7.3 and 64.8 ± 6.8 % at 7 years, respectively (P = 0.36), and were not significantly different. However, the second relapse incidence of late relapse (34.7 ± 7.1 %) was higher than that of very late relapse (15.5 ± 5.1 %, P = 0.03). The second relapse risk was low for very late relapse ALL, which suggests that these patients should be treated without allogeneic HSCT.
    International Journal of Hematology 11/2014; 101(1). DOI:10.1007/s12185-014-1710-z · 1.68 Impact Factor

Full-text (2 Sources)

Available from
May 29, 2014