Elsevier

European Journal of Cancer

Volume 39, Issue 18, December 2003, Pages 2579-2583
European Journal of Cancer

Who should be treating adolescents and young adults with acute lymphoblastic leukaemia?

https://doi.org/10.1016/j.ejca.2003.09.005Get rights and content

Abstract

Although several cancers have a peak incidence during adolescence and young adulthood, the patients in this age group are arbitrarily referred to either paediatric or adult oncologists and, consequently, treated on different protocols. Recent reports show that paediatric oncologists are more likely to enroll patients in clinical trials, and that adolescents who are treated on paediatric protocols have a better outcome than their counterparts who are managed by adult oncologists. These observations were also noted in adolescents with acute lymphoblastic leukaemia (ALL), a disease with a bimodal peak incidence in early childhood and late adulthood. Recently, investigators have become aware that patients in the adolescent and young adult age group might be falling through the cracks because of the rigid organisation of the medical care system. In this article, I present some of the current challenges in the treatment of ALL in adolescents and young adults and propose strategies to improve outcome in these patients.

Introduction

Referral patterns allow for cancer patients 13–21 years of age to be treated either by paediatric or by adult oncologists. Thus, 2 16-year-old patients with the same disease who are referred to the same cancer centre may well receive different protocols if one is referred to paediatrics and the other to adult services. Lately, efforts have been made to design combined paediatric/adult protocols for diseases like Hodgkin's lymphoma and osteosarcoma that have a peak incidence in the adolescent and young adult (AYA) age group. This strategy should also apply to leukaemia. ALL is a heterogeneous disease with a bimodal age distribution—an early peak between 2 and 6 years of age and a second peak in patients over 40 years. Younger children and older adults therefore constitute most of the 2500 children and 2000 adults diagnosed with ALL in the United States of America (USA) every year. Although 80% of children are cured with current ALL regimens 1, 2, less then 40% of adults with ALL are long-term survivors, despite implementation of treatment strategies that have proved successful in children 3, 4. Moreover, although adolescents and young adults tolerate and respond to current therapies better than older patients, their prognosis is not as good as children with leukaemia. Possible reasons for these discrepancies will be presented in this article along with suggestions for future strategies.

Section snippets

What makes adolescents and young adults different?

An understanding of the factors influencing ALL outcome in the AYA age group is needed to improve on current therapeutic strategies. Different factors—among them the disease itself, the host and the treatment—contribute to the inferior outcome in AYA compared with younger children.

Outcome of AYA-ALL on different protocols

Significant progress has been made in the treatment of ALL in both paediatric and adult patients over the past 40 years (Table 2) 12, 22, 23, 24. However, whereas around 80% of children 1–10 years old are long-term survivors with current therapies, only 30–40% of adult patients are cured. Adolescents and young adults have an intermediate outcome. Numerous paediatric studies have confirmed that adolescents have a worse prognosis than children 1–9 years of age, despite more intensive therapies 2,

Lessons learned

Although the outcome for AYA with ALL is intermediate between that of younger children and older adults in all published studies, available data indicate that patients in this age group fare better on paediatric protocols. These observations were made using a retrospective analysis of relatively heterogeneous populations, with different therapies, little data on actual drug dosages delivered, and different treatment delivery settings. As a consequence, it is difficult to draw meaningful

Future directions

In adolescents and young adults with ALL, disease biology, tolerance to therapy and outcome are similar. At present, the relatively small numbers of ‘AYA’ with ALL are treated, according to loose referral patterns, either with adult or paediatric protocols. Over the past two decades, immunophenotyping, cytogenetics and molecular genetics have helped design therapies that target leukaemia subtypes. The latest advances in molecular genetics and proteomics should promote the use of more selective,

References (34)

  • K.K. Hussein et al.

    Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy

    Blood

    (1989)
  • P.S. Gaynon et al.

    Children's Cancer Group trials in childhood acute lymphoblastic leukaemia1983–1995

    Leukemia

    (2000)
  • C.H. Pui et al.

    Long-term results of total therapy studies 11, 12 and 13a for childhood acute lymphoblastic leukemia at St. Jude Children's Research Hospital

    Leukemia

    (2000)
  • H.M. Kantarjian et al.

    Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia

    J. Clin. Oncol.

    (2000)
  • C.H. Pui et al.

    Acute lymphoblastic leukemia

    N. Engl. J. Med.

    (1998)
  • M. Arico et al.

    Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia

    N. Engl. J. Med.

    (2000)
  • S. Jeha et al.

    Treatment of acute lymphoblastic leukemia in adolescents and young adults

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