Elsevier

The Lancet

Volume 345, Issue 8943, 21 January 1995, Pages 143-148
The Lancet

Articles
Intensification of treatment and survival in all children with lymphoblastic leukaemia: results of UK Medical Research Council trial UKALL X

https://doi.org/10.1016/S0140-6736(95)90164-7Get rights and content

Abstract

The UK Medical Research Council trial MRC UKALLX was designed to investigate the benefit of one or two courses of additional intensification therapy in children with acute lymphoblastic leukaemia receiving standard treatment. From 1985 to 1990 1612 children, comprising more than 90% of eligible cases in the UK, were treated with intensive induction therapy, central nervous system directed therapy with cranial irradiation and intrathecal methotrexate, and continuing treatment for 2 years. 1171 children were randomised to receive additional intensification therapy at 5 weeks, 20 weeks, both, or neither. At follow-up of at least 3 years disease-free survival for all children at 5 years was 62% (95% confidence interval [Cl] 60·0-64·4), a significant improvement over the 56% (53·0-59·6) found in the preceding MRC UKALL trial. The 5-year disease-free survival was 71% (65·5-76·1) for children randomised to two blocks of intensification therapy, this being significantly better than the 62% (56·6-68·0), 61% (55·7-67·1), and 57% (50·9-62·7) rates for the groups randomised to one intensification block at 5 weeks, one at 20 weeks, and no intensification, respectively. The benefits of intensification therapy were seen irrespective of clinical factors known to influence outcome such as age, sex, and initial leucocyte count. We conclude that the addition of two courses of intensification therapy has produced a 14% improvement in disease-free survival and an 11% improvement in overall survival for the randomised patients. This additional treatment is of benefit to all children with acute lymphoblastic leukaemia, even those traditionally deemed at lower risk of relapse.

References (32)

  • Sj White et al.

    Allocation of patients to treatment groups in a controlled clinical study

    Br J Cancer

    (1978)
  • R. Peto et al.

    Design and analysis of randomized clinical trials requiring prolonged observation of each patient II: analysis and examples

    Br J Cancer

    (1977)
  • D. Cox

    The contribution of statistical methods to cancer research

    Cancer

    (1991)
  • Dr Miller et al.

    Prognostic factors and therapy in acute lymphoblastic leukemia of childhood: CCG-141

    Cancer

    (1983)
  • H. Riehm et al.

    Therapy Results in five ALL-BFM studies since 1970: implications of risk factors for prognosis

    Haematol Blood Transfusion

    (1987)
  • Cited by (245)

    • Developing a conceptual model of teenage and young adult experiences of cancer through meta-synthesis

      2013, International Journal of Nursing Studies
      Citation Excerpt :

      A recent trend to extend the upper age eligibility criteria of some paediatric treatment protocols to allow older teenagers and young adults to be included. This is in response to evidence of superior survival for young people treated on paediatric regimes (Boissel et al., 2003; Chessells et al., 1995; Hallbook et al., 2006). An example of this is the paediatric Acute Lymphoblastic Leukaemia protocol UKALL 2003 where reported symptom severity was greater for young people, for example avascular necrosis.

    • Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: A randomized study by the Children's Oncology Group (POG 9404)

      2011, Blood
      Citation Excerpt :

      Methotrexate, a folate analog which inhibits intracellular folate-requiring enzymes, has been a vital component of successful ALL treatment regimens regardless of immunophenotype. Doses have ranged from 20 mg/m2 given orally on a weekly schedule to 33.6 g/m2 given by 24-hour intravenous infusion.14,19,23-26 The optimal dose and route of administration are still debated.

    • Early Relapse in ALL Is Identified by Time to Leukemia in NOD/SCID Mice and Is Characterized by a Gene Signature Involving Survival Pathways

      2011, Cancer Cell
      Citation Excerpt :

      Leukemia cell clearance in response to steroid treatment is evaluated and has been used as a prognostic marker for almost 20 years, demonstrating inferior survival for patients responding poorly to prednisone (Gajjar et al., 1995; Riehm et al., 1987; Schrappe et al., 1998, 2000a, 2000b). In addition, detection of residual leukemia cells at submicroscopic levels after remission induction therapy (minimal residual disease, MRD) qualifies for HR treatment (Chessells et al., 1995; Conter et al., 2010; Flohr et al., 2008; Steinherz et al., 1996; van Dongen et al., 1998). Early identification of patients with high risk for relapse has led to improved outcome.

    • Pediatric Leukemias and Lymphomas

      2010, Leibel and Phillips Textbook of Radiation Oncology, Third Edition
    View all citing articles on Scopus

    Members during MRC UKALL X listed at end of paper

    View full text