Comparison of neurocognitive functioning in children previously randomly assigned to intrathecal methotrexate compared with triple intrathecal therapy for the treatment of childhood acute lymphoblastic leukemia.
OBJECTIVE
For the majority of children with acute lymphoblastic leukemia (ALL), CNS prophylaxis consists of either intrathecal (IT) methotrexate or triple IT therapy (ie, methotrexate with both cytarabine and hydrocortisone). The long-term neurotoxicities of these two IT strategies have not yet been directly compared.


METHODS
In this multisite study, 171 children with standard-risk ALL, age 1 to 9.99 years at diagnosis, previously randomly assigned to IT methotrexate (n = 82) or to triple IT therapy (n = 89) on CCG 1952, underwent neurocognitive evaluation by a licensed psychologist at a mean of 5.9 years after random assignment.


RESULTS
Patients who received IT methotrexate had a mean Processing Speed Index that was 3.6 points lower, about one fourth of a standard deviation, than those who received triple IT therapy (P = .04) after analysis was adjusted for age, sex, and time since diagnosis. Likewise, 19.5% of children in the IT methotrexate group had a Processing Speed Index score in the below-average range compared with 6.9% in the triple IT therapy group (P = .02). Otherwise, the groups performed similarly on tests of full-scale intelligence quotient, academic achievement, attention/concentration, memory, and visual motor integration. The association of treatment with measures of cognitive functioning was not modified by sex or age at diagnosis. In the post-therapy period, there were no group differences in special education services, neurologic events, or use of psychotropic medications.


CONCLUSIONS
This study did not show any clinically meaningful differences in neurocognitive functioning between patients previously randomly assigned to IT methotrexate or triple IT therapy except for a small difference in processing speed in the IT methotrexate group.
Kadan-Lottick
Nina S
NS
Section of Pediatric Hematology-Oncology, Yale University School of Medicine, New Haven, CT, USA. Nina.Kadan-Lottick@Yale.Edu
Brouwers
Pim
P
Breiger
David
D
Kaleita
Thomas
T
Dziura
James
J
Northrup
Veronika
V
Chen
Lu
L
Nicoletti
Megan
M
Bostrom
Bruce
B
Stork
Linda
L
Neglia
Joseph P
JP
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001288:Attention / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects*; D003430:Cross-Sectional Studies; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007223:Infant; D007278:Injections, Spinal; D007361:Intelligence Tests; D016014:Linear Models; D008297:Male; D008568:Memory / Q000187:drug effects; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011597:Psychomotor Performance / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine; D006854:Hydrocortisone; D008727:Methotrexate