Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for neurocognitive deficits that are associated with treatment, individual, and environmental factors. This study examined the impact of different methotrexate (MTX) and corticosteroid treatment strategies on neurocognitive functioning in children with high-risk B-lineage ALL. Methods Participants were randomly assigned to receive high-dose MTX with leucovorin rescue or escalating dose MTX with PEG asparaginase without leucovorin rescue. Patients were also randomly assigned to corticosteroid therapy that included either dexamethasone or prednisone. A neurocognitive evaluation of intellectual functioning (IQ), working memory, and processing speed (PS) was conducted 8 to 24 months after treatment completion (n = 192). Results The method of MTX delivery and corticosteroid assignment were unrelated to differences in neurocognitive outcomes after controlling for ethnicity, race, age, gender, insurance status, and time off treatment; however, survivors who were age < 10 years at diagnosis (n = 89) had significantly lower estimated IQ ( P < .001) and PS scores ( P = .02) compared with participants age ≥ 10 years. In addition, participants who were covered by US public health insurance had estimated IQs that were significantly lower ( P < .001) than those with US private or military insurance. Conclusion Children with high-risk B-lineage ALL who were age < 10 years at diagnosis are at risk for deficits in IQ and PS in the absence of cranial radiation, regardless of MTX delivery or corticosteroid type. These data may serve as a basis for developing screening protocols to identify children who are at high risk for deficits so that early intervention can be initiated to mitigate the impact of therapy on neurocognitive outcomes.

Described school issues for children with cancer. The relationship between school performance and both acute and long-term consequences of the type of cancer, radiation therapy, and chemotherapy is presented. Results of studies of the cognitive and academic effects of cranial radiation and chemotherapy are reviewed, and a developmental model for understanding the emergence of deficits over time is described. Important considerations regarding assessment, classification, and individualized educational intervention are addressed, including specific suggestions of strategies that may aid in helping the child with cancer in the school setting.Each year in the United States, approximately 6500 children under 15 years of age are diagnosed with some form of cancer (Fernbach & Vietti, 1991). While there are many different types of cancer in children, the two most common are leukemias and brain tumors, which combine to account for approximately 50% of all cases (Robison, Mertens, & Neglia, 1991). For all children with cancer, there are multiple obstacles to normal school attendance and academic performance, including frequent school absenteeism, acute effects of the malignancy, acute effects of chemotherapy (medications), and infections (Chesler & Barbarin, 1986). For children with leukemias or brain tumors, school problems may additionally be related to changes across time in the structure and/or function of the brain following treatment with chemotherapy administered into the cerebrospinal fluid (intrathecal chemotherapy) and/or radiation therapy to the brain Mulhem, 1994). Although a number of design and methodologic difficulties with the research in this area have been described (Brown & Madan-Swain, 1993;Butler & Copeland, 1993;Mulhern, 1994), empirical and clinical findings suggest that children treated with cranial radiation or cranial radiation combined with intrathecal chemotherapy have significant risk for persistent learning problems long after treatment has terminated (Mulhern, 1994;Mulhern, Crisco, & Kun, 1983), with a somewhat lower risk associated with intrathecal chemotherapy alone (Brown & Madan-Swain, 1993;

Background The incidence of isolated testicular relapse (ITR) of acute lymphoblastic leukemia (ALL) has decreased with contemporary treatment strategies, but outcomes are suboptimal with a 58% 5-year overall survival (OS). This study aimed to improve outcome in patients with ITR of B-cell ALL (B-ALL) occurring after 18 months of first clinical remission using intensive systemic chemotherapy and to decrease long-term sequelae by limiting use of testicular radiation. Procedure Forty patients in first ITR of B-ALL were enrolled. Induction (dexamethasone, vincristine, daunorubicin, and intrathecal triple therapy) was preceded by one dose of high-dose methotrexate (MTX, 5 g/m2). Following induction, 25 of 26 patients who had persistent testicular enlargement underwent testicular biopsy. Eleven had biopsy-proven disease and received bilateral testicular radiation (24 Gy), whereas twenty-nine did not. Results Overall 5-year event-free survival (EFS)/OS was 65.0 ± 8.8%/73.1 ± 8.3%, with 5-year EFS 62.1±11.0% vs. 72.7±14.4% for patients who did not receive radiation therapy (XRT) (n=29) compared with those who did (n = 11), respectively (P = 0.64). There were six second bone marrow relapses and six second ITRs. The proportion of second relapses was similar in the patients that received testicular radiation and those who did not. However, the 5-year OS was similar for patients who did not receive XRT (72.6 ± 10.2%) compared with those who did (72.7 ± 14.4%) (P = 0.85). Conclusions A 5-year OS rate of 73.1 ± 8.3% was obtained in children with first ITR of B-ALL occurring after 18 months of CR1 (length of first clinical remission) using intensive chemotherapy and limiting testicular radiation.