Neurodevelopmental outcome of infants with acute lymphoblastic leukemia: a Children's Cancer Group report.
BACKGROUND
Infants diagnosed with acute lymphoblastic leukemia (ALL) are considered the patient subgroup at the highest risk for central nervous system (CNS) disease, both at presentation and as an isolated extramedullary relapse. In addition, they are highly vulnerable to adverse developmental sequelae from CNS-directed therapy.


METHODS
Thirty patients younger than 12 months at diagnosis (12 males, 18 females) in first hematologic remission were evaluated after completion of ALL therapy (mean age = 62.1 months; standard deviation = 17.2 months; range = 38-102 months). CNS-directed treatment included very high dose infusions of methotrexate (MTX) and intrathecal cytarabine and MTX. Three patients had meningeal leukemia that required additional therapy. Children were administered the McCarthy Scales of Children's Abilities, and parents completed a sociodemographic questionnaire to obtain information about occupation and education.


RESULTS
Mean scores on all 6 cognitive and motor indices of the McCarthy Scales were in the average range (Verbal = 52.0; Perceptual = 53.6; Quantitative = 49.6; General Cognitive Index [GCI] = 102.1; Memory = 49.2; Motor = 51.0). Score distributions for each neurodevelopmental index were comparable to age-based population standards. One patient obtained a GCI that exceeded 2 standard deviations above the mean; none scored more than 2 standard deviations below. There was no report of developmental disabilities or neurologic disorders for any of the patients. Risk factors, including age at diagnosis, gender, additional CNS-directed treatment, and family socioeconomic status, were not associated with developmental outcome.


CONCLUSIONS
Test findings indicated a generally positive neurodevelopmental outcome for ALL patients diagnosed in infancy who were treated with very high dose MTX as CNS-directed therapy. Combined with the reduction in the isolated CNS relapse rate achieved by the Children's Cancer Group (CCG) clinical trial CCG-107, the results of this study represent a substantial improvement in neurodevelopmental outcome for very young patients compared with infants treated for ALL in the past.
Kaleita
T A
TA
University of California Los Angeles School of Medicine, USA.
Reaman
G H
GH
MacLean
W E
WE
Sather
H N
HN
Whitt
J K
JK
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D001925:Brain Damage, Chronic / Q000453:epidemiology / Q000209:etiology*; D003072:Cognition Disorders / Q000453:epidemiology / Q000209:etiology; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D002658:Developmental Disabilities / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D002955:Leucovorin / Q000627:therapeutic use; D017254:Leukemic Infiltration / Q000517:prevention & control; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000009:adverse effects; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D009069:Movement Disorders / Q000453:epidemiology / Q000209:etiology; D009483:Neuropsychological Tests; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011597:Psychomotor Performance; D012074:Remission Induction; D012306:Risk; D012959:Socioeconomic Factors; D017741:Survivors; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D003561:Cytarabine; D014750:Vincristine; D015122:Mercaptopurine; D001215:Asparaginase; D002955:Leucovorin; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin