Program: Oral and Poster Abstracts
Type: Oral
Session: 902. Health Services and Outcomes Research – Malignant Diseases: Toxicities of Therapy
Methods: Caregiver report data were analyzed for 1426 5+ year survivors of childhood ALL who were diagnosed between 1970 and 1999 and between 12 to 17 years of age at follow-up, and 609 sibling controls. Cognitive and behavior problems were measured with the Behavior Problem Inventory (BPI). Academic problems were defined as special education placement (yes/no). Chi-Square tests were used to compare the frequency of elevated BPI scores (≥90th percentile) and special education placement in survivors versus siblings. Multivariable logistic regression was used to examine the association between CRT and chemotherapy doses (Table 1) and cognitive, behavior, and academic problems, adjusting for sex and age at diagnosis (<5 years, ≥5 years). In a subset of 736 survivors for whom longitudinal data were available, associations were examined between cognitive/behavior problems and special education placement during adolescence and self-reported educational attainment as adults (mean [range] age = 28.0 [25.0–37.3]).
Results: Compared to siblings, survivors were more likely to have elevated symptoms of anxiety-depression, inattention-hyperactivity, headstrong behavior, and social withdrawal, as well as higher rates of special education placement (Table 2). Relative to no CRT, treatment that included CRT at a dose of <20 Gy increased the risk for anxiety-depression (OR=1.69, [95%CI, 1.25-2.30]), inattention-hyperactivity (OR=1.25, [1.16, 2.00]), and social withdrawal (OR=1.98, [1.51, 2.61]). Moreover, risk of special education placement was increased for survivors treated with <20 Gy CRT (OR=1.89, [1.47, 2.45]) and ≥20 Gy (OR=2.45, [1.93-3.91]). Among survivors treated without CRT, cumulative doses of intrathecal or intravenous methotrexate (MTX) were not associated with risk for cognitive, behavior, or learning problems. Survivors with cognitive or behavior problems, and those who participate in special education during adolescence were less likely to graduate from college as adults (Table 2*).
Conclusion: Adolescent survivors of childhood ALL, especially those treated with CRT, are at significantly increased risk for cognitive, behavior, and academic problems that adversely impact adult outcomes. Participation in special education did not remediate this risk, as survivors receiving services were less likely to graduate college as adults. Interventions designed to improve adolescent neurobehavioral functioning should be prioritized.
Table 1.
|
% |
Mean ± SD |
Age at diagnosis < 5 years |
79 |
3.74±1.82 |
≥ 5 years |
21 |
|
Sex - Male |
54 |
|
Seizures or strokes after diagnosis - Yes |
7 |
|
CRT None |
50 |
|
<20 Gy |
31 |
|
≥ 20 Gy |
12 |
|
IT MTX <230 mg |
44 |
|
≥ 230 mg |
56 |
|
IV MTX None |
55 |
|
<4.3 g/m2 |
21 |
|
≥ 4.3 g/m2 |
24 |
|
Cytarabine None |
29 |
|
Yes |
71 |
|
Anthracyclines None |
48 |
|
< 300 mg/m2 |
39 |
|
≥ 300 mg/m2 |
13 |
|
Alkylating agents None |
41 |
|
Yes |
59 |
5716.26 ± 5424.92 |
Dexamethasone None |
26 |
|
Yes |
74 |
|
Table 2.
|
Survivors |
|
|
College Graduation* |
|
Siblings |
p |
OR |
95% CI |
||
Cognitive and behavior problems |
|
|
|
|
|
Antisocial |
14% |
11% |
0.0800 |
2.28 |
1.34, 3.90 |
Anxiety-Depression |
17% |
11% |
0.0003 |
1.55 |
1.02, 2.35 |
Headstrong |
22% |
14% |
0.0002 |
1.52 |
1.03, 2.23 |
Inattention - Hyperactivity |
24% |
14% |
<0.0001 |
3.04 |
2.04, 4.54 |
Social Withdrawal |
25% |
12% |
<0.0001 |
1.31 |
0.92, 1.88 |
Academic Problems |
|
|
|
|
|
Special Education – Yes |
34% |
14% |
<0.0001 |
4.29 |
2.95, 6.22 |
Disclosures: No relevant conflicts of interest to declare.
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