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Value of intravenous 6-mercaptopurine during continuation treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a randomized phase III trial (58881) of the EORTC CLG

Leukemia volume 19, pages 721–726 (2005)Cite this article

Abstract

Between November 1990 and November 1996, EORTC Children Leukemia Group conducted a randomized trial in de novo acute lymphoblastic leukemia and lymphoblastic non-Hodgkin's lymphoma patients using a Berlin–Frankfurt–Munster protocol to evaluate the monthly addition of intravenous 6-mercaptopurine (i.v. 6-MP) (1 g/m2) to conventional continuation therapy comprising per oral MTX weekly and 6-MP daily. Only during the first 18 months of the randomization period, 6-MP p.o. was interrupted for 1 week after each i.v. 6-MP. A total of 877 patients was randomized to either no i.v. 6-MP (Arm A) or additional i.v. 6-MP (Arm B). A total of 217 relapses (91 in Group A vs 128 in Group B) and 13 deaths in CR (5 vs 8) were reported; a total of 134 patients (55 vs 79) died. The median follow-up was 7.6 years. At 8 years, the disease-free survival rate was lower (P=0.005) in Arm B (69.1% (s.e.=2.2%)) than in Arm A (77.9% (s.e.=2.0%)), and the hazard ratio was 1.45 (95% CI 1.12–1.89). In conclusion, as delivered in this study, i.v. 6-MP was detrimental to event-free survival.

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Acknowledgements

This work was supported in part by grants from Télévie 2001 (Grant No 7.4561.01) and 5U10CA11488-18S2 and 2U10CA11488-19 through 5U10-CA11488-34 from the National Cancer Institute. Purinethol (6-mercaptopurine) for intravenous use, a product of Wellcome, was provided free of charge by the National Cancer Institute. The contents of this work are solely the responsibility of the authors and do not represent the official view of the National Cancer Institute or of Wellcome. Additional members of the EORTC CLG participated to this study: B Nelken (Lille), A Babin-Boilletot (Strasbourg), C Béhar (Reims), N Francotte (Montegnée), B Lescoeur (Paris), G Margueritte (Montpellier), F Millot (Poitiers), X Rialland (Angers) and F Méchinaud (Nantes). The members of different subcommittees: Dr M Malet (Caen), A Falkenrodt (Strasbourg), M Fournier (Lille), Dr N Dastugue (Toulouse), Drs A-M Manel and M-P Pages (Lyon). A warm thank to the previous data managers: I VandeVelde and G Solbu. Thanks to E Jacqz-Aigrain and G Milano for their careful review of an earlier version of this paper and their input in the Discussion.

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Author notes

  1. E Vilmer: Deceased.

Authors and Affiliations

  1. Department of Pediatrics, Akademisch Ziekenhuis - VUB, Brussels, Belgium

    J van der Werff ten Bosch & J Otten

  2. EORTC Data Center, Brussels, Belgium

    S Suciu & C Waterkeyn

  3. A. Lacassagne Center, Nice, France

    A Thyss & N Sirvent

  4. Debrousse Hospital, Lyon, France

    Y Bertrand & N Philippe

  5. Department of Pediatrics, Escolar San Joao Hospital, Porto, Portugal

    L Norton

  6. Department of Pediatrics, CHR Lille, Lille, France

    F Mazingue

  7. Pediatric Hemato-Oncology, U.Z. Gasthuisberg, Leuven, Belgium

    A Uyttebroeck

  8. Hematology, Hautepierre, Strasbourg, France

    P Lutz

  9. Hematology, Children's Hospital, Toulouse, France

    A Robert

  10. Pediatric Hematology, CHRU, Caen, France

    P Boutard

  11. Hemato-Oncology, HUDE, Brussels, Belgium

    A Ferster

  12. Pediatric Hematology, Saint Jacques Hospital, Besançon, France

    E Plouvier

  13. Paola Children's Hospital, Antwerpen, Belgium

    P Maes

  14. Hematology, American Hospital, Reims, France

    M Munzer

  15. Department of Pediatrics, CHR La Tronche, Grenoble, France

    D Plantaz

  16. Department of Pediatrics, Hospital Citadelle, Liège, Belgium

    M-F Dresse

  17. Department of Pediatrics, CHC Espérance, Montegnée, Belgium

    P Philippet

  18. Hemato-Immunology, Robert Debré Hospital, Paris, France

    E Vilmer

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on behalf of the Children's Leukemia Group (CLG) of the European Organisation for Research and Treatment of Cancer (EORTC)

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Correspondence to J Otten.

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van der Werff ten Bosch, J., Suciu, S., Thyss, A. et al. Value of intravenous 6-mercaptopurine during continuation treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a randomized phase III trial (58881) of the EORTC CLG. Leukemia 19, 721–726 (2005). https://doi.org/10.1038/sj.leu.2403689

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