Results
Of 626 eligible pediatric HCT survivors surveyed, 199 participated
(50.3% female) at a median age of 37.8 years (range 18-61) at survey
and median 27.6 years (range 1-46) from transplant (Table 1). Of note,
59 (29.6%) of participants underwent transplant at age <10
years and 21 (10.6%) were transplanted at age <3 years. The
majority underwent transplantation for malignant conditions, including
106 patients with acute leukemia (53.3%) and 20 with chronic leukemia
(10.1%). Among non-malignant conditions, 44 patients (22.1%) received
transplants for hematologic conditions, most commonly aplastic anemia.
Nine patients (4.5%) received transplants for immunodeficiencies,
histiocytic disorders, or other indications. Most (175/199 patients)
initially received allogeneic transplants (87.9%) and a subset of 20
patients (10.1%) received multiple transplants. Across all transplants,
132 patients (66.3%) underwent conditioning with total body irradiation
(TBI), with 123 (61.8%) receiving ≥1000cGy. Eighteen (9.0%) also
received additional cranial irradiation prior to TBI (median 1200cGy,
range 480-5400); 1 additional patient received cranial irradiation alone
without TBI. The prevalence of moderate/severe hearing issues and
history of stroke/seizures was 40/198 (20.2%) and 21/197 (10.7%),
respectively. Compared with non-participants, participants were more
likely to be female, currently older, and transplanted at an earlier
age, but did not differ across other demographic or clinical
characteristics (Supplemental Table S1).
On the CCSS-NCQ, 32.5% of survivors reported problems with task
efficiency, 25.4% with memory, 21.8% with emotional regulation, and
18.9% with organization compared with an expected 10% in the general
population (Table 2; all p<0.01 ). Results were similar
after application of inverse probability weights, with 33.0% reporting
impairment with task efficiency, 27.6% with memory, 22.6% with
emotional regulation, and 18.4% with organization (Supplemental Table
S2). In unweighted analysis, female survivors reported more issues with
emotional regulation and memory relative to males. Race/ethnicity,
current age, underlying diagnosis, year of transplant, number of
transplants, or history of cGVHD were not associated with a significant
difference in CCSS-NCQ scores. Characteristics associated with
impairments in most or all CCSS-NCQ domains included hearing issues,
history of stroke or seizure, and self-reported sleep disturbances.
Survivors >25 years of age with less educational
achievement also reported significantly worse scores in all domains (allp<0.05 ). Survivors who received cranial irradiation
were more likely to report impaired scores in task efficiency and
organization compared with survivors who did not receive any radiation
or those treated with TBI alone (p<0.05 ). In
multivariable regression analysis adjusted for sex and current age,
hearing issues were independently associated with impaired task
efficiency (OR 2.71, 95% CI 1.19-6.17) and organization (OR 3.39, 95%
CI 1.38-8.32), while history of stroke or seizure was independently
associated with impaired emotional regulation (OR 4.78, 95% CI
1.81-12.6) and memory (OR 3.98, 95% CI 1.46-10.8; Figure 1 and
Supplemental Table S3). Sleep disturbances were associated with
impairments across all CCSS-NCQ domains. Younger age at transplant was
generally associated with increased risk of impairments in CCSS-NCQ
domains, although estimates were not statistically significant in
adjusted models. Additionally, results were essentially unchanged if
models were further adjusted by radiation exposure.
Respondents reported average Neuro-QoL (49.6±0.7) compared with an
expected mean score of 50 in the general population (p=0.52 ;
Table 3). The proportion with impaired cognitive quality of life with
T-score <40 was 19.1% compared with 16% expected in the
general population sample (p=0.23 ).21 These
values were similar after accounting for inverse probability weights,
with mean Neuro-QoL score of 49.2±0.7 and 20.5% impairment
(Supplemental Table S2). In unweighted analysis, characteristics
associated with lower Neuro-QoL scores included younger age
(<10 years) at HCT, prior cranial irradiation, hearing issues,
history of stroke or seizure, and sleep disturbances (allp<0.05 ). Sex, race/ethnicity, current age, underlying
diagnosis, year of transplant, number of transplants, or history of
cGVHD were not associated with a significant difference in Neuro-QoL
scores. In survivors >25 years old, lower Neuro-QoL scores
were associated with less educational achievement, defined as less than
college completion (p<0.01 ). In multivariable
regression analysis adjusted for sex and current age, impaired Neuro-QoL
was independently associated with hearing issues (OR 4.79, 95% CI
1.91-12.0), history of stroke or seizure (OR 5.22, 95% CI 1.73-15.7),
and sleep disturbances (OR 6.90, 95% CI 2.53-18.9; Figure 1 and
Supplemental Table S3). Younger age (<10 years) at time of
transplant was not significantly associated with impaired Neuro-QoL in
multivariable analysis compared with age ≥ 10 years (OR 1.63, 95% CI
0.64-4.16).