This, the largest study of adult survivors of childhood ALL, found that nearly one quarter of patients (24%) reported high levels of mood disturbance (a POMS score of nearly twice the mean of POMS scores from other cancer survivor studies). Survivors treated with High CRT had a greater percentage of mood disturbance than survivors treated with High MTX, No-Low MTX, or No-Low CRT. However, multivariate analyses indicated treatment group was not a direct mediator of adult mood status. Instead, treatment acted to increase or decrease risk rates depending on the survivor’s educational achievement. In contrast, being a preadolescent at diagnosis was a strong, direct predictor of mood disturbance. Female patients, minority (non-white) male patients, female patients with a special education history, and high-school dropouts with a special education history were also at significantly greater risk.
Being a preadolescent at diagnosis increased risk for adult mood disturbance almost four-fold, and this effect was not modulated by educational achievement or treatment dose. These data are in keeping with studies indicating that a young age at diagnosis is predictive of lower school achievement8
and more negative life outlook28
but stand in contrast to others showing no effect of age at diagnosis on coping and social functioning5,29
or a reverse effect (general psychologic functioning worse for survivors who were older at diagnosis).19
Equivocal findings may be due to the cross-study variations in survivor age at assessment. The impact of age at diagnosis on psychologic problems may change as survivors move from late adolescence to adulthood and face new life challenges. Developmental issues are further implicated by the mood disturbance rate here (24%), which replicates the extent of psychologic problems found in recent studies of young adult survivors of childhood cancer29–31
but stand in contrast to those combining teens and young adults.8,28,32
Survivors with past attendance in special education classes were more than twice as likely to show mood disturbance, and this risk increased six-fold among female patients. Assuming special education history is a proxy for neurocognitive deficits, these data suggest that female patients are not only at greater risk for cognitive deficits after pediatric cancer treatment,9,20,21
but such deficits may also increase their risk for mood disturbance. Dropouts with a special education history were also at high risk for mood disturbance.
A heightened risk for mood disturbance among No or Low-dose treatment groups led to surprising protective effects of high-dose treatment in interaction with education variables. For example, high-dose treatment and a special education history among college attendees significantly reduced risk relative to No-Low doses. Also, survivors who attended college or who were high school dropouts were less likely to have mood disturbance if treated with High CRT than if treated with No-Low doses. High MTX likewise reduced risk for mood disturbance among high school dropouts compared with No-Low doses. This protective effect of high-dose treatment did not occur among high school graduates; both High CRT and High MTX were risk factors for mood disturbance compared with No-Low doses. These surprising findings may be data anomalies related to small sample size in subgroups. Or, perhaps survivors who overcome the disadvantage of high-dose treatment or learning problems and go to college despite these handicaps may be particularly resilient psychologically. In support, survivor scores on a measure of self-esteem were highly correlated with total POMS scores (r
= −0.54; P
= .01) and were higher among survivors who attended college than for those who did not attend college (P
Although being female or nonwhite increased risk for mood disturbance, nonwhite male patients were at comparatively greatest risk. This sex by race or ethnicity effect is unique to the present study because of the statistical power achieved here by the large sample. The associations between mood disturbance and negative perceptions of current health and cancer’s impact on ability to work are in keeping with previous evidence that subjective perceptions of the cancer experience and its impact play a significant role in psychologic late effects.8,28,30
However, without prospective data, it is not possible to determine whether such perceptions are underlying mediators of treatment and education interactions, direct causal factors in mood disturbance, or a consequence of current mood state.
The present study has numerous advantages over previous research. The sample is homogeneous for cancer type (ALL) and developmental stage (young adults), representative of many communities (multisite), and of sufficient sample size to stratify/statistically control for multiple variables. Given these strengths, the conclusion about the relative value of treatment severity in predicting mood disturbance is unequivocal. Objective measures of treatment severity offer some prognostic value for identifying at-risk groups but are overshadowed by other person and situation variables. Just as trauma severity is limited in predicting those at risk for posttraumatic stress disorder,30,34–37
treatment severity is limited as a predictor of mood disturbance.
Other conclusions are less definitive as a result of several methodologic limitations. First, POMS elevations are not synonymous with the presence of a mental disorder. Also, the cutoff score used here was chosen to represent a level of mood disturbance that is likely to be functionally significant, but further research on the validity of the POMS for predicting functional health is needed. Second, establishing that a relationship exists between long-term mood disturbance and treatment, demographic, and perceptual variables does not elucidate the mechanisms of such associations. For example, increased mood disturbance in those younger at diagnosis may simply reflect longer exposure to parental anxiety generated by the cancer; high rates of posttraumatic stress disorder have been found among mothers of children who have survived cancer.34,31,38
Third, recent studies of coping, social relationships, and self-image8,28,29,32
confirm that there are multiple aspects to psychologic health after cancer. Future studies of psychologic well-being in pediatric cancer survivors may be greatly enhanced by data reflecting multiple time points, informants (eg, parents, spouses/partners, doctors, teachers, and friends), and levels of analyses (eg, psychophysiologic and behavioral).
In summary, one quarter of this large sample of young adult survivors of childhood ALL reported mood disturbance, but CRT and MTX dose were not direct risk factors alone. With the exception of nonwhite male ethnicity/sex and preadolescent age at diagnosis, treatment and demographic risk factors occurred only in conjunction with postdiagnosis educational experiences that are potentially amenable to intervention. These findings hold out hope that greater educational support provided during and after pediatric cancer treatment may offset the potentially negative sequelae of high-dose regimens.