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

M. N. Dufourg; J. Landman-Parker; M. F. Auclerc; C. Schmitt; Y. Perel; G. Michel; P. Levy; G. Couillault; V. Gandemer; M. D. Tabone; F. Demeocq; J. P. Vannier; T. Leblanc; G. Leverger; A. Baruchel

HAL : hal-00597629, version 1

PubMed : 17170721

DOI : 10.1038/sj.leu.2404495

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Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 21, 2 (2007) 238-47

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

M. N. Dufourg, J. Landman-Parker¹, M. F. Auclerc, C. Schmitt², Y. Perel, G. Michel³, P. Levy^{4, 5}, G. Couillault, V. Gandemer, M. D. Tabone, F. Demeocq, J. P. Vannier⁶, T. Leblanc⁷, G. Leverger¹, A. Baruchel⁸

Dufourg MN, Landman-Parker J, Auclerc MF, Schmitt C, Perel Y, Michel G, Levy P, Couillault G, Gandemer V, Tabone MD, Demeocq F, Vannier JP, Leblanc T, Leverger G, Baruchel A. Collaboration(s)

(02/2007)

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/m(2)/week (LD MTX, n=81) or HD MTX at 1.5 g/m(2)/2 weeks x 6 (n=77). Intermediate-risk group (IR, n=672) were randomized to LD MTX (n=290) or HD MTX at 8 g/m(2)/2 weeks x 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.

1 :	Service d'hématologie-immunologie-oncologie pédiatrique

2 :	GANIL - Grand Accélérateur National d'Ions Lourds

3 :	Bordeaux 2 Laboratoire de Psychologie EA «Santé et qualité de vie»

4 :	Georgia Tech Lorraine

5 :	ESIM - Epidémiologie des maladies infectieuses et modélisation

6 :	Pediatric Hematology and Oncology

7 :	Table Mountain Facility, Jet Propulsion Laboratory

8 :	Service d'hématologie pédiatrique

Domaine

Sciences du Vivant/Santé publique et épidémiologie


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