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Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97.

Abstract：

:In this study, the long-term outcome of 1818 patients treated in five consecutive clinical trials (the cooperative study group for childhood acute lymphoblastic leukaemia (COALL) 82, 85, 89, 92 and 97) from 24 cooperating centres in Germany is reported. The probability of event-free survival (pEFS) improved significantly from the first two trials conducted in the 1980s (COALL 82 and COALL 85) to the three trials conducted in the 1990s (COALL 89, 92 and 97) (P=0.001). Through all COALL studies, age > or =10 years and initial white blood cell count (WBC) > or =50 x 10(9)/l and pro-B immunophenotype were of significant prognostic relevance. A refinement of risk assessment has been achieved by in vitro drug sensitivity testing in COALL 92 and 97. In patients with very sensitive leukaemic cells, therapy could be reduced without loss of efficacy. In COALL 97, a further improvement in risk stratification was gained by the molecular assessment of minimal residual disease (MRD) under treatment, which proved to have a superior prognostic effect when compared with in vitro drug sensitivity testing. Importantly, the gradual reduction in central nervous system (CNS) irradiation led to a decreased incidence of brain tumours as a second malignancy. In general, the prevention of treatment-related late effects will be one of the major issues in future studies. It remains to be shown whether prolonged infusions of anthracyclines, which have been implemented into the COALL studies after equal efficacy compared with short-time infusions was confirmed, will be associated with fewer cardiac late effects. Another way to prevent late effects may be a more refined risk assessment allowing for a reduction in cumulative treatment burden. A great challenge in the future will be to improve the overall treatment results, which very likely can only be achieved by the identification of molecularly defined subgroups to which novel, rational therapeutic strategies can be applied.

journal_name

Leukemia

journal_title

Leukemia

authors

Escherich G,Horstmann MA,Zimmermann M,Janka-Schaub GE,COALL study group.

doi

10.1038/leu.2009.249

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

298-308

issue

eissn

0887-6924

issn

1476-5551

pii

leu2009249

journal_volume

pub_type

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Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97.