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Therapy

Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children

Leukemia volume 21, pages 238–247 (2007)Cite this article

Abstract

The objective of the study was to assess acute neurotoxicity associated with triple intrathecal therapy (TIT)±high-dose methotrexate (HD MTX) in children with acute lymphoblastic leukemia (ALL). 1395 children were enrolled on FRALLE 93 protocol from 1993 to 1999. Lower-risk group (LR, n=182) were randomized to weekly low-dose MTX at 25 mg/m2/week (LD MTX, n=81) or HD MTX at 1.5 g/m2/2 weeks × 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m2/2 weeks × 4 (n=316). Higher-risk group (HR, n=541) prednisone-responder patients received LD MTX and cranial radiotherapy. HR group steroid resistant cases were grafted (autologous or allogenic). TIT (MTX, cytarabine and methylprednisolone) was given every 2 weeks during 16–18 weeks and every 3 months during maintenance therapy in LR and IR patients. 52 patients (3.7%) developed neurotoxicity. Isolated seizures: n=15 (1.1%), peripheral and spinal neuropathy: n=17 (1.2%) and encephalopathy: n=20 (1.4%). Age >10 years was significantly associated with neurotoxicity (P=0.01) and use of HD MTX is associated with encephalopathy (P=0.03). Sequels are reported respectively in 60 and 33% of spinal neuropathy and encephalopathy cases. Current strategies tailoring risk of neurological sequels has to be defined.

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Acknowledgements

We acknowledge David Young for editing. Preliminary report of the study has been reported at the annual meeting of the American Society of Hematology (ASH) in 1999 (Blood 1999, 94(10) (Suppl 1) 1285).

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Authors and Affiliations

  1. Service d’hématologie et d’oncologie pédiatrique Hôpital d’Enfant Armand Trousseau, AP-HP, Paris,, France

    M N Dufourg, J Landman-Parker, M D Tabone & G Leverger

  2. Service d’hématologie pédiatrique Hôpital St Louis, AP-HP, Paris, France

    M F Auclerc, T Leblanc & A Baruchel

  3. Service de pédiatrie II hospital d’Enfant Vandoeuvre les Nancy, Paris, France

    C Schmitt

  4. Département de pédiatrie CHU Pellerin Bordeaux, Paris, France

    Y Perel

  5. Service d’hématologie pédiatrique CHU La Timone, Marseille, Paris, France

    G Michel

  6. Département d’informatique médicale Hôpital Tenon, AP-HP, Paris, France

    P Levy

  7. Service de pédiatrie CHR de Limoges,

    G Couillault

  8. Service de pédiatrie CHR Rennes,

    V Gandemer

  9. Service d’hématologie CHR Clermont Ferrand,

    F Demeocq

  10. Département de pédiatrie CHR Rouen, for the French cooperative group FRALLE,

    J P Vannier

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Correspondence to J Landman-Parker.

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Dufourg, M., Landman-Parker, J., Auclerc, M. et al. Age and high-dose methotrexate are associated to clinical acute encephalopathy in FRALLE 93 trial for acute lymphoblastic leukemia in children. Leukemia 21, 238–247 (2007). https://doi.org/10.1038/sj.leu.2404495

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