CNS late-effects after ALL therapy in childhood. Part III: neuropsychological performance in long-term survivors of childhood ALL: impairments of concentration, attention, and memory.
OBJECTIVE
To date, the event free survival (EFS) after treatment of childhood acute lymphoblastic leukemia (ALL) attains 80%. The survivor group is growing steadily. Therefore, the primary purpose of our study is to define the neuropsychological function and to describe which central nervous system (CNS) functions are impaired following the German ALL-BFM and COALL protocols for CNS-negative patients.


METHODS
In a cross-sectional multicenter study 121 subjects, long-term survivors of childhood ALL in first continuous complete remission were investigated. Seven years ago, the subjects were treated as standard or medium risk patients according to ALL-BFM 81, ALL-BFM 83, or COALL 82 protocols, receiving comparable treatments. According to different CNS-prophylaxes, two subgroups were compared in the study: the non-cranially irradiated MTX-group (methotrexate-group) (n = 38) and the cranially irradiated RT-group (radiotherapy-group) (with MTX i.th.) (n = 83). Intellectual and cognitive abilities of these groups were evaluated using standardized psychometric techniques. The Kaufman factors Verbal Comprehension, Perceptual Organisation and Freedom from Distractibility were calculated. Demographical and clinical data collected at the time of the diagnosis were compared between both groups. The different prognoses for patients within both groups were taken into account using a defined risk factor. Analysis of variance was conducted to relate intellectual performance to age, gender, and CNS-treatment.


RESULTS
The RT-group exhibited a lower Full Scale IQ than the MTX-group (101.2 +/- 15.9 vs. 109.9 +/- 14.9, P = 0.031). Particularly for the Kaufman factor Freedom from Distractibility the RT-group showed the lower scores (96.9 +/- 14.1 vs. 105.5 +/- 12.6, P = 0.037). Significant interactions between gender and CNS prophylactic treatment were observed for Full Scale IQ (P = 0.008), Verbal IQ (P = 0.012), Performance IQ (P = 0.024), Verbal Comprehension (P = 0.004), and Perceptual Organisation (P = 0.032).


CONCLUSIONS
Cranial irradiation in combination with MTX therapy was associated with deficits in attention, concentration, and the ability of sequencing and processing, measured by the Kaufman factor Freedom from Distractibility. Our results support the strategy of avoiding prophylactic CNS irradiation in low risk patients.
Langer
Thorsten
T
Department of Pediatric Oncology, University Hospital for Children and Adolescents, Erlangen, Germany.
Martus
Peter
P
Ottensmeier
Holger
H
Hertzberg
Holger
H
Beck
Jörn D
JD
Meier
Walburga
W
D000293:Adolescent; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001288:Attention; D001932:Brain Neoplasms / Q000517:prevention & control / Q000556:secondary; D002490:Central Nervous System / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000139:chemically induced*; D016371:Cranial Irradiation / Q000009:adverse effects*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007361:Intelligence Tests; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D012307:Risk Factors
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate