Who should be treating adolescents and young adults with acute lymphoblastic leukaemia?
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)
- et al.
A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukaemiacancer and leukemia group B study 8811
Blood
(1995) - et al.
In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia
Blood
(1997) - et al.
Clinical significance of cytogenetic abnormalities in adult acute lymphoblastic leukemia
Blood
(1998) - et al.
Intensive chemotherapy for Philadelphia-chromosome-positive acute lymphoblastic leukaemia
Lancet
(1994) - et al.
Clinical characteristics and treatment outcome of childhood acute lymphoblastic leukemia with the t(4;11)(q21;q23)a collaborative study of 40 cases
Blood
(1991) - et al.
Six year follow up of the clinical significance of karyotype in acute lymphoblastic leukemia
Cancer Genet. Cytogenet.
(1989) - et al.
Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults
Blood
(1988) - et al.
Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from children with hyperdiploid (greater than 50 chromosomes) B-lineage acute lymphoblastic leukemiaa Pediatric Oncology Group study
Blood
(1992) - et al.
Correlation of P-glycoprotein expression and function in childhood acute leukemiaA Children's Cancer Group study
Blood
(1996) - et al.
Acute lymphoblastic leukemia in childhood
Pediatr. Clin. North Am.
(1988)
Treatment of acute lymphoblastic leukemia in adults with intensive induction, consolidation, and maintenance chemotherapy
Blood
Children's Cancer Group trials in childhood acute lymphoblastic leukaemia1983–1995
Leukemia
Long-term results of total therapy studies 11, 12 and 13a for childhood acute lymphoblastic leukemia at St. Jude Children's Research Hospital
Leukemia
Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia
J. Clin. Oncol.
Acute lymphoblastic leukemia
N. Engl. J. Med.
Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia
N. Engl. J. Med.
Treatment of acute lymphoblastic leukemia in adolescents and young adults
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