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BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991–1996)

Leukemia volume 16, pages 1099–1111 (2002)Cite this article

Abstract

Modern treatment strategies, consisting of intensive chemotherapy and cranial irradiation, have remarkably improved the prognosis for children with acute lymphoblastic leukemia. However, patients with a potential for cure are at risk of severe acute and late adverse effects of treatment. Furthermore, in 25–30% of patients treatment still fails. The objectives of the DCLSG study ALL 8 were to decrease the toxicity and to increase the effectivity of BFM-oriented treatment. Decrease of toxicity was aimed at by confirmation of the results of the previous DCLSG study ALL-7, showing that the majority (94%) of children with ALL can succesfully be treated with BFM-oriented therapy without cranial irradiation, and by reduction of treatment for standard risk (SRG) patients. To increase the cure rate in medium risk (MRG) patients the efficacy of high doses of intravenous 6-mercaptopurine (HD-6MP) during protocol M and in SRG patients the efficacy of high doses of L-asparaginase (HD-L-ASP) during maintenance treatment was studied in randomized studies. Patient stratification and treatment were identical to protocol ALL-BFM90, with the following differences: no prophylactic cranial irradiation, SRG patients received only phase 1 of protocol I. Four hundred and sixty-seven patients entered the protocol: 170 SRG, 241 MRG and 56 HRG patients. The 5 years event-free survival rate for all patients was 73% (s.e. 2%); for SRG, MRG and HRG patients 85% (s.e. 3%), 73% (s.e. 3%) and 39% (s.e. 7%), respectively. In patients >1 year of age at diagnosis unfavorable prognostic factors were male sex, >25% blasts in the bone marrow at day 15 and initial white blood cell count (WBC) >50 × 109/l. The cumulative risk of CNS relapse rate was 5% (s.e. 1%) at 5 years. These results confirm that the omission of cranial irradiation in BFM-oriented treatment does not jeopardize the overall good treatment results, nor does early reduction of chemotherapy in SRG patients. No benefit was observed from treatment intensification with HD-L-ASP in SRG patients, nor from HD-6MP in MRG patients.

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Acknowledgements

The DCLSG thanks the I-BFM-SG members Prof dr H-J Riehm (Hannover), Prof dr H Gadner (Vienna), Prof dr G Masera (Monza) and Dr M Schrappe (Hannover) for their support.

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Authors and Affiliations

  1. Dutch Childhood Leukemia Study Group (DCLSG), The Hague, The Netherlands

    WA Kamps, JPM Bökkerink, FGAJ Hakvoort-Cammel, AJP Veerman, RS Weening, ER van Wering, JF van Weerden, J Hermans & A van der Does-van den Berg

  2. Beatrix Children's Hospital, University Hospital, Groningen, The Netherlands

    WA Kamps

  3. Department of Pediatrics, University Hospital, Nijmegen, The Netherlands

    JPM Bökkerink

  4. Sophia Children's Hospital, University Hospital, Rotterdam, The Netherlands

    FGAJ Hakvoort-Cammel

  5. Department of Pediatrics, University Hospital Vrije Universiteit, Amsterdam, The Netherlands

    AJP Veerman

  6. Emma Kinderziekenhuis Academic Medical Center, Amsterdam, The Netherlands

    RS Weening

  7. Department of Medical Statistics, Leiden University Medical Center, The Netherlands

    J Hermans

  8. Department of Clinical Genetics/Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands

    R Slater

  9. Dutch Workgroup on Cancer Genetics and Cytogenetics (NWKGC), The Netherlands

    R Slater, E van den Berg & WG Kroes

  10. Department of Medical Genetics, University of Groningen, Groningen, The Netherlands

    E van den Berg

  11. Department of Clinical Genetics, University of Amsterdam, The Netherlands

    WG Kroes

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  1. WA Kamps
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Additional information

DCLSG Board Members 1991: W A Kamps, P J van Dijken, K Hählen, F A E Nabben, A Postma, J A Rammeloo, G A M de Vaan, Eth. Korthof, A J P Veerman

NWKGC Members 1991: R Slater (Amsterdam), A Hagemeijer-Hausman (Rotterdam), E van den Berg (Groningen), A Hamers (Maastricht), C G Beverstock (Leiden), A Geurts van Kessel (Nijmegen), D E M Olde Weghuis (Utrecht), W Kroes (Amsterdam), M Blij-Philipsen (Veldhoven)

Appendix

Appendix

Table 9 Appendix: DCLSG protocol ALL8 (treatment)
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Kamps, W., Bökkerink, J., Hakvoort-Cammel, F. et al. BFM-oriented treatment for children with acute lymphoblastic leukemia without cranial irradiation and treatment reduction for standard risk patients: results of DCLSG protocol ALL-8 (1991–1996). Leukemia 16, 1099–1111 (2002). https://doi.org/10.1038/sj.leu.2402489

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