Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice.
OBJECTIVE
We evaluated cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL). CNS therapy consisted of cranial irradiation (CRT) or no radiation. Children were also randomized to single intravenous high-dose methotrexate (HD-MTX) or conventional-dose methotrexate (CD-MTX) during induction, and all patients received intrathecal (IT) and systemic continuation chemotherapy.


METHODS
Sixty-six patients treated for ALL on Dana-Farber Cancer Institute protocol 87-01 were evaluated by standardized cognitive and achievement tests. These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, respectively. All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m2) or HD-MTX (4 g/m2) with leucovorin rescue.


RESULTS
There was no difference in cognitive outcomes between radiated and unirradiated patients (P > .4). However, the HD-MTX/CRT combination was associated with decreased intelligence quotient (IQ estimate, 9.3 points) for girls only (P < .08). A specific deficit in verbal coding and memory was documented for all patients (P < .0001).


CONCLUSIONS
We conclude the following: (1) 18 Gy CRT per se was not an independent toxic agent for cognitive outcome; (2) HD-MTX during induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding was a consistent finding that was independent of CRT, which implicates some component of chemotherapy, possibly prednisone, as a CNS toxin.
Waber
D P
DP
Division of Psychology, Children's Hospital, Boston, MA 02115, USA.
Tarbell
N J
NJ
Fairclough
D
D
Atmore
K
K
Castro
R
R
Isquith
P
P
Lussier
F
F
Romero
I
I
Carpenter
P J
PJ
Schiller
M
M
D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000009:adverse effects*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007360:Intelligence / Q000187:drug effects* / Q000528:radiation effects*; D007361:Intelligence Tests; D008297:Male; D008569:Memory Disorders / Q000209:etiology*; D008727:Methotrexate / Q000008:administration & dosage; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D011878:Radiotherapy / Q000009:adverse effects; D012737:Sex Factors
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D008727:Methotrexate