Verbal Cognitive Functioning and Learning in Girls Treated for Acute Lymphoblastic Leukemia By Chemotherapy With or Without Cranial Irradiation

Neuropsychological problems have frequently been reported following treatment of Acute Lymphoblastic Leukemia (ALL), however, partly because of the heterogeneity of the previously studied samples, the specific nature of these deficits is still a matter of debate. These problems, however, appear to be related more to the combination of cranial radiation therapy (CRT) and intrathecal chemotherapy (ITC) than to ITC alone. In this study, we evaluated a homogenous group of l9 girls between the ages of 7 and 11 years, 30 months after the completion of treatment. Nine received cranial radiation and chemotherapy and 10 were treated with chemotherapy alone. The patients were compared to 10 normal healthy controls. Neuropsychological tests included the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), the California Verbal Learning Test-Children's Version (CVLT-C), and the Calculation and Passage Comprehension subtests of the Woodcock-Johnson Psycho-Educational Battery-Revised. Results confirmed the presence of a verbal learning deficit in ALL girls treated with the combination of ITC and CRT. The ITC and CRT group scored significantly lower than the healthy controls on the Passage Comprehension subtest and on 5 of the 6 verbal subtests of the WISC-III. Furthermore, compared to nonirradiated patients and healthy normal controls, the ITC and CRT group was impaired on the Freedom from Distractibility index of the WISC-III, indicating an auditory-verbal attention deficit. On the CVLT-C, the ITC and CRT group was particularly impaired on the second half of the learning trials compared to the other two groups, showing a plateau in their performance. The ITC group was not different from the healthy control group, suggesting a less detrimental effect of the ITC alone on verbal abilities. Globally, these results indicate a deficit affecting auditory attention and verbal learning in girls who receive ITC and CRT, which may suggest the necessity for special educational assistance for these children.

[1]  P. Dobkin,et al.  A comprehensive model of the development of mental handicap in children treated for acute lymphoblastic leukaemia: A synthesis of the literature , 2000 .

[2]  F. D. Armstrong,et al.  Neurobehavioral issues in childhood cancer , 1999 .

[3]  H. Taylor,et al.  Pediatric Neuropsychology: Research, Theory, and Practice , 1999 .

[4]  S. Warschausky,et al.  WISC-III index growth curve characteristics following traumatic brain injury. Wechsler Intelligence Scale for Children--Third Edition. , 1999, Journal of clinical and experimental neuropsychology.

[5]  P. Britton,et al.  Attentional ability among survivors of leukaemia , 1999, Archives of disease in childhood.

[6]  P. Isquith,et al.  Cognitive sequelae of treatment in childhood acute lymphoblastic leukemia: cranial radiation requires an accomplice. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  R. Magel,et al.  A comparison of tests for the k-sample, non-decreasing alternative. , 1995, Statistics in medicine.

[8]  D. Roman,et al.  Neuropsychological effects of cranial radiation: current knowledge and future directions. , 1995, International journal of radiation oncology, biology, physics.

[9]  R. Butler,et al.  Neuropsychologic effects of cranial irradiation, intrathecal methotrexate, and systemic methotrexate in childhood cancer. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  D. Bearison,et al.  Neuropsychological Late Effects , 1994 .

[11]  A. Kingma,et al.  Association of 1800 cGy cranial irradiation with intellectual function in children with acute lymphoblastic leukaemia , 1994, The Lancet.

[12]  V. Anderson,et al.  Intellectual, educational, and behavioural sequelae after cranial irradiation and chemotherapy. , 1994, Archives of disease in childhood.

[13]  R. Butler,et al.  Neuropsychological effects of central nervous system prophylactic treatment in childhood leukemia: methodological considerations. , 1993, Journal of pediatric psychology.

[14]  A. Madan-Swain,et al.  Cognitive, Neuropsychological, and Academic Sequelae in Children with Leukemia , 1993, Journal of learning disabilities.

[15]  Nancy Mather,et al.  Woodcock-Johnson Psycho-Educational Battery-Revised: Recommendations and Reports , 1992 .

[16]  J W Goldwein,et al.  Whole-brain irradiation and decline in intelligence: the influence of dose and age on IQ score. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Gilles R. Ducharme,et al.  Asymptotic Theory for Bootstrap Methods in Statistics , 1991 .

[18]  R. Mulhern,et al.  A prospective comparison of neuropsychologic performance of children surviving leukemia who received 18-Gy, 24-Gy, or no cranial irradiation. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  R. Gelber,et al.  LATE EFFECTS OF CENTRAL NERVOUS SYSTEM TREATMENT OF ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDHOOD ARE SEX‐DEPENDENT , 1990, Developmental medicine and child neurology.

[20]  J. Fletcher,et al.  Neurobehavioral effects of central nervous system prophylactic treatment of cancer in children. , 1988, Journal of clinical and experimental neuropsychology.

[21]  R. Mulhern,et al.  Memory function in disease-free survivors of childhood acute lymphocytic leukemia given CNS prophylaxis with or without 1,800 cGy cranial irradiation. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  B. Sachs,et al.  Postirradiation treatment outcomes for children with acute lymphocytic leukemia: clarification of risks. , 1987, Journal of pediatric psychology.

[23]  J. Fletcher,et al.  Neuropsychological sequelae of childhood cancer in long-term survivors. , 1985, Pediatrics.

[24]  J. Holland,et al.  Effects of different forms of central nervous system prophylaxis on neuropsychologic function in childhood leukemia. , 1984, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  L. Jannoun Are cognitive and educational development affected by age at which prophylactic therapy is given in acute lymphoblastic leukaemia? , 1983, Archives of disease in childhood.

[26]  L. Robison,et al.  PRESYMPTOMATIC CENTRAL NERVOUS SYSTEM THERAPY IN PREVIOUSLY UNTREATED CHILDHOOD ACUTE LYMPHOBLASTIC LEUKAEMIA: COMPARISON OF 1800 RAD AND 2400 RAD A Report for Children's Cancer Study Group , 1981, The Lancet.

[27]  A. R. Jonckheere,et al.  A DISTRIBUTION-FREE k-SAMPLE TEST AGAINST ORDERED ALTERNATIVES , 1954 .

[28]  W. Bleyer Chemoradiotherapy interactions in the central nervous system. , 1998, Medical and pediatric oncology.

[29]  J. Holland,et al.  A comparative study of the long term psychosocial functioning of childhood acute lymphoblastic leukemia survivors treated by intrathecal methotrexate with or without cranial radiation , 1998, Cancer.

[30]  R. Reeb,et al.  Neuropsychological Functioning in Survivors of Childhood Leukemia. , 1998 .

[31]  M. Lezak Neuropsychological assessment, 3rd ed. , 1995 .

[32]  S. Sallan,et al.  Neuropsychological diagnostic profiles of children who received CNS treatment for acute lymphoblastic leukemia: The systemic approach to assessment , 1992 .

[33]  D. Poplack,et al.  Memory and Learning Sequelae in Long‐term Survivors of Acute Lymphoblastic Leukemia: Association with Attention Deficits , 1990, The American journal of pediatric hematology/oncology.

[34]  D. Esseltine,et al.  Cognitive function in long survivors of childhood acute lymphoblastic leukemia. , 1989, Pediatric hematology and oncology.

[35]  L. Jannoun,et al.  Long-term psychological effects of childhood leukemia and its treatment. , 1987, Pediatric hematology and oncology.

[36]  B. Efron The jackknife, the bootstrap, and other resampling plans , 1987 .

[37]  L. Robison,et al.  Factors associated with IQ scores in long-term survivors of childhood acute lymphoblastic leukemia. , 1984, The American journal of pediatric hematology/oncology.

[38]  J. Fletcher,et al.  Neuropsychologic assessment of long-term survivors of childhood leukemia. , 1984, The American journal of pediatric hematology/oncology.