Neuropsychological outcomes from a randomized trial of triple intrathecal chemotherapy compared with 18 Gy cranial radiation as CNS treatment in acute lymphoblastic leukemia: findings from Dana-Farber Cancer Institute ALL Consortium Protocol 95-01.
OBJECTIVE
We evaluated late neuropsychological toxicity in children treated for standard-risk acute lymphoblastic leukemia (ALL) who were randomly assigned to receive either cranial radiation therapy (CRT) with double intrathecal (IT) chemotherapy or intensive triple IT chemotherapy (no CRT) as CNS-directed therapy.


METHODS
Between 1996 and 2000, 164 children with standard-risk ALL treated on Dana-Farber Cancer Institute Consortium Protocol 95-01 were randomly assigned to receive either 18 Gy CRT delivered in twice daily fractions (0.9 [DOSAGE ERROR CORRECTED] Gy) with double IT therapy (methotrexate and cytarabine) or intensive triple IT drug (methotrexate, cytarabine and hydrocortisone) without CRT. Neuropsychological testing was completed at a median 6 years postdiagnosis for 79 children (CRT, n = 39; triple IT, n = 40), all of whom were in continuous complete remission.


RESULTS
Cognitive function for both groups was solidly in the average range, with no consistent group differences in basic cognitive skills. Children treated on the CRT plus double IT arm did, however, exhibit less fluent output and were less effective at modulating their behavior by parent report.


CONCLUSIONS
This randomized trial revealed only subtle differences 6 years after diagnosis between children who received CNS therapy as CRT plus double IT drug or as intensive triple IT drug. In most situations where comparable therapeutic efficacy can be achieved without CRT, it is preferable to do so. Where therapeutically necessary, however, CRT at lower doses may not add risk for significant neurotoxicity.
Waber
Deborah P
DP
Division of Psychology, Department of Psychiatry, Children's Hospital, Boston, MA 02115, USA. deborah.waber@childrens.harvard.edu
Turek
Jennifer
J
Catania
Lori
L
Stevenson
Kristen
K
Robaey
Philippe
P
Romero
Ivonne
I
Adams
Heather
H
Alyman
Cheryl
C
Jandet-Brunet
Christine
C
Neuberg
Donna S
DS
Sallan
Stephen E
SE
Silverman
Lewis B
LB
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002493:Central Nervous System Diseases / Q000175:diagnosis* / Q000209:etiology; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation / Q000009:adverse effects*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007223:Infant; D007278:Injections, Spinal; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*
D005938:Glucocorticoids; D003561:Cytarabine; D006854:Hydrocortisone; D008727:Methotrexate