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 ¼ 0.001). Through all COALL studies, age X10 years and initial white blood cell count (WBC) X50 Â 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 treatmentrelated 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.

Absence of biallelic TCRγ deletion predicts induction failure and poorer outcomes in childhood T‐cell acute lymphoblastic leukemia

“…Although the use of intensive chemotherapy has enabled patients with T-cell ALL to fare as well as patients with B-cell precursor ALL in some studies, the outcomes are significantly worse for the patients with T-cell ALL in most treatment protocols [3][4][5][6][7][8][9][10][11][12][13][14][15]. Chromosomal alterations, including numbers and translocations, have helped to classify pediatric patients with B-cell precursor ALL and improve treatment outcomes in the past three decades [16].…”

PTEN microdeletions in T-cell acute lymphoblastic leukemia are caused by illegitimate RAG-mediated recombination events

“…28 Normal thymocytes were isolated from thymic tissue obtained from children undergoing cardiac surgery. 24,29 Informed consents were in accordance with the institutional review boards of the Erasmus MC (Rotterdam, The Netherlands), the ethics committee of the City of Hamburg, Germany, the Hospital Sta.…”

Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome

“…3 In the Nordic countries, the relapse rate was close to 40% between 1981 and 1993 and only 30% remained in long-term second remission. 4 Over the last two decades, the reported relapse rates have been 15-20% [1][2][3]5,6 in the developed countries and the overall survival after relapse approximately 40-70%, depending on the follow-up time and the risk groups involved. [7][8][9][10][11][12] Since 1992, all children aged one year and over diagnosed with pre-B and T-cell ALL in the Nordic countries (Denmark, Finland, Iceland, Norway, Sweden) have been treated according to a common Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL protocol.…”