-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

877 Cognitive, Behavior and Academic Problems in Adolescent Survivors of Childhood Acute Lymphoblastic Leukemia (ALL): A Report from the Childhood Cancer Survivor Study

Health Services and Outcomes Research – Malignant Diseases
Program: Oral and Poster Abstracts
Type: Oral
Session: 902. Health Services and Outcomes Research – Malignant Diseases: Toxicities of Therapy
Monday, December 7, 2015: 4:30 PM
Chapin Theater (W320), Level 3 (Orange County Convention Center)

Lisa M Jacola, PhD1*, Kim Edelstein, PhD, CPsych2*, Wei Liu, PhD3*, Ching-Hon Pui, MD4, Robert J. Hayashi, MD5*, Nina Kadan-Lottick, MD, MSPH6*, Deokumar Srivastava, PhD3*, Tara O Henderson, MD, MPH7, Leslie L. Robison, PhD, MPH8, Gregory T. Armstrong, MD, MSCE8* and Kevin R. Krull, PhD9*

1Psychology, St. Jude Children's Research Hospital, Memphis, TN
2Pencer Brain Tumor Centre, Princess Margaret Cancer Center, Toronto, ON, Canada
3Biostatistics, St. Jude Children's Research Hospital, Memphis, TN
4Oncology, St. Jude Children's Research Hospital, Memphis, TN
5Pediatric Hematology/Oncology, Washington University School of Medicine, St. Louis, MO
6Pediatrics, Yale Univ. School of Medicine, New Haven, CT
7Comer Children's Hospital, University of Chicago, Chicago, IL
8Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN
9Psychology, Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN

Introduction: Over the past 30 years, survival rates for childhood ALL have improved and neurotoxicity has been reduced by largely replacing cranial radiation therapy (CRT) with additional systemic and intrathecal therapy. However, survivors treated without CRT may still be at risk for long-term neurocognitive deficits and reduced quality of life. Neurobehavioral problems during adolescence are particularly problematic as increased environmental demands for self-direction and higher order cognition are expected. As existing studies of cognition and behavior in adolescent survivors are limited by small samples, single-site data collection, and short follow-up intervals, we examined the prevalence of and risk factors for cognitive, behavior, and academic problems in adolescent survivors of childhood ALL using the Childhood Cancer Survivors Study (CCSS) cohort.

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.

Previous Abstract | Next Abstract >>

*signifies non-member of ASH