Abstract
Purpose
Parents’ stress levels are high prior to their child's hematopoietic stem cell transplant (HSCT) and during transplant hospitalization, usually abating after discharge. Nevertheless, a subgroup of parents continues to experience frequent anxiety and mood disruption, the causes of which are not well understood. The purpose of this study was to assess whether clinical complications of HSCT could explain variation in parents’ recovery of emotional functioning.
Methods
Pediatric HSCT recipients (n=165) aged 5 to 18 and their parents were followed over the first year post-transplant. Health-related quality of life (HRQL) assessments and medical chart reviews were performed at each time period (baseline, 45 days, 3, 6, and 12 months). We tested the association between clinical complications (acute and chronic graft versus host disease - aGVHD and cGVHD, organ toxicity, and infection) and longitudinally measured parental emotional functioning, as assessed by the Child Health-Ratings Inventories (CHRIs). The models used maximum likelihood estimation with repeated measures.
Results
In adjusted analyses covering the early time period (45 days and 3 months), aGVHD grade ≥ 2, intermediate or poor organ toxicity, and systemic infection were associated with decreases in mean parental emotional functioning of 5.2 (p=0.086), 5.8 (p=0.052), and 5.1 (p=0.023) points, respectively. In the later time period (6 and 12 months) systemic infection was associated with a decrease of 20 points (p<0.0001). cGVHD was not significantly associated.
Conclusions
When children experience clinical complications after HSCT, parental emotional functioning can be impacted. Intervening at critical junctures could mitigate potential negative consequences for parents and their children.
Keywords: Pediatric hematopoietic stem cell transplant, Parental emotional functioning, Parental distress, Transplant-related toxicity
Introduction
Parents of children with life-threatening illnesses are vulnerable to psychological distress that can impair their ability to manage the child's care and result in increased distress for the child [1, 2]. Furthermore, as children suffer serious complications from treatment, parents may experience even greater distress.
HSCT offers potentially life-saving therapy to children with high risk malignancies and other life-threatening diseases of hematologic, immunologic, and metabolic origin. However, the treatment is intense and often produces many acute and delayed sequelae, including infection, acute and chronic graft versus host disease (aGVHD and cGVHD), and organ toxicity [3].
A more complete understanding of how these complications affect parents’ mental health could provide opportunities to intervene at critical junctures, and thus prevent potential lapses in the child's care and deterioration in family functioning [4]. A review [5] of parental stress and pediatric HSCT noted the lack of information on HSCT-specific stressors, and the need for disease-specific measures. This report addresses both of those gaps.
The primary objective of this study was to assess the relationship between clinical complications of HSCT and parental emotional functioning over the course of the child's recovery during the first year post-transplant. We also identified demographic and clinical predictors of parents’ emotional functioning at baseline.
Methods
Participants
The data are from the Journeys to Recovery study [6] of health-related quality of life (HRQL), which followed 165 pediatric HSCT recipients aged 5 to 18 years over the first year post-transplant at six transplant centers nationwide. For each child enrolled, one parent also participated (self-selected as the one spending more time with the child at the transplant center). Assessments were conducted before the child's transplant (baseline) and at 45 days, 3, 6, and 12 months post-transplant. The study was approved by the Institutional Review Board (IRB) at Tufts Medical Center and at all clinical, recruiting sites before enrollment was commenced in keeping with the 1964 Declaration of Helsinki. Parents provided written consent for their own participation and permission for the participation of the minor child. Age-appropriate assent was obtained from minor children as dictated by the policies of the local IRBs. Children reaching the age of majority (18 years) also provided written consent.
Outcome
The primary assessment tool for the Journeys to Recovery study was the Child Health-Ratings Inventories (CHRIs), a health-related quality of life (HRQL) questionnaire with versions for both the parent and the patient specific to two patient age groups (5-12 year olds, and 13-18 year olds) [7, 8]. The CHRIs contains a General Health Module, a Hematopoietic Stem Cell Transplant (HSCT) Module, and a demographics questionnaire. Parent participants were also invited to complete secondary measures, including selected modules for mood, anxiety, and adjustment disorders of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID).
The outcome for all analyses in this report is the parent's emotional functioning, from the parental CHRIs-General Health module. The 7-item self-administered domain is conceptually similar to the five-item mental health domain of the SF-36 [9]. The construct of emotional functioning as measured by the CHRIs refers to the past week and contains items addressing mood, anxiety, and hassles. Item content and response sets of this domain are presented in Table 1. Using the half scale rule, which requires that at least half the items in a scale be completed, the seven items were averaged together to create a summary score, and then transformed to a 100-point scale. The half scale rule was only rarely necessary (< 4% of assessments). The score is not standardized, but is scaled from 0 to 100, with higher scores connoting better functioning. For example, subjects who have been worried, sad, hassled, and stressed some of the time and also happy and calm some of the time would score in the middle.
Table 1.
Content of the CHRIs-General parental emotional functioning domain
| Question | Please select the one response that is most applicable |
|---|---|
| During the past week, how nervous, worried, or fidgety have you felt? | Not at all |
| A little | |
| Some | |
| A lot | |
| A whole lot | |
| During the past week, how happy or sad have you been? | Really happy |
| Pretty happy | |
| Happy | |
| A little sad | |
| Sad | |
| During the past week, how often:a | All of the time |
| a. have you felt calm and peaceful | Most of the time |
| b. have you felt sad, down hearted, and blue | Some of the time |
| c. have you been a happy person | A little of the time |
| d. have you felt hassled | None of the time |
| e. have you felt stressed |
These five questions were asked in a matrix form with a separate response elicited for each question.
The score is a good proxy for related modules of the SCID. The area under the receiver operating characteristic (ROC) curve for predicting a threshold or subthreshold disorder using only the CHRIs parental emotional functioning score was 0.75 [10], indicating that the score has good performance in discriminating between subjects with and without a disorder.
Medical Information
Medical Information was collected at each assessment time point, using standardized data collection forms based on validated toxicity scales [11-15]. Information was obtained from the medical record by trained research staff after formal central training and under the supervision of the clinical transplant staff at each of the collaborating sites. All medical chart information was additionally reviewed for accuracy and consistency by Dr. Parsons, who is a transplant physician.
Statistical Analysis
Baseline Analysis
Descriptive analyses were performed for baseline variables including parent characteristics (age, gender, education, race, ethnicity, and threshold and subthreshold Axis I Disorder from the SCID), child characteristics (age, gender, number of siblings, causal diagnosis for transplant (i.e., malignancy yes/no), and duration of illness), type of transplant (autologous, related donor, or unrelated donor), and timing of the baseline assessment (before or during the preparative regimen). T-tests, analysis of variance, and simple linear regression were used to estimate the relation between the baseline variables and parent's emotional functioning at baseline. Linear regression was used for multivariable analysis, which also adjusted for center. Any variable significant at p < 0.20 in univariate analyses was a candidate for inclusion in the multivariable regression model. Variables were retained based on backward elimination and significance level alpha=0.05.
Longitudinal Analysis
The independent variables of interest were the clinical complications of HSCT. The time periods were 45 days and 3 months for early clinical complications (aGVHD[13, 14], Bearman maximum overall toxicity [15] (Appendix 1) and infection [11]); and 6 and 12 months for late complications (cGVHD and infection). [11, 12] HRQL assessments and medical chart reviews were performed at each time period. Infection and organ toxicity were recorded if they were present during the week prior to the HRQL assessment. Date of onset, maximum overall grade, and current status of aGVHD and cGVHD were recorded at each relevant time period. We dichotomized aGVHD at grade 2 or higher, as an indicator of severity. We also tested a composite variable for early clinical complications: aGVHD (grade 2 or higher) or toxicity (intermediate or poor) or systemic infection or unplanned subsequent transplant within 100 days. Parent and child characteristics (except for SCID diagnosis), type of transplant, and timing of baseline assessment were tested for association with the outcome in models including all time points. Variables significant at p=0.20 were candidates for the models testing clinical complications.
We used maximum likelihood estimation with repeated measures in SAS Proc Mixed to account for within-subject correlation, with an unstructured covariance matrix. Models were adjusted for baseline characteristics and time period. We assessed whether data were missing not at random (MNAR) [16] by plotting mean trajectories of emotional functioning. Separate trajectories were plotted for those who never missed an assessment, those who missed at least once but only for logistical reasons, and those who ever missed an assessment due to distress or the child's medical condition (data not shown). Since the latter group was not consistently lower, we assumed that missing outcome data were missing at random (MAR).
Results
Completion rates ranged from 100% at baseline to a low of 80% at 3 months, averaging 88% over the six time points. The mean (standard deviation) of parent emotional functioning was 49.4 (18.5), 56.8 (18.1), 55.1 (20.4), 58.3 (21.0), and 65.1 (19.4) at baseline, 45 days, 3 months, 6 months, and 12 months, respectively.
Baseline analysis
A summary of the baseline variables appears in Table 2. Only Axis I disorder and transplant center were significantly associated with parent's emotional functioning at baseline (Table 3). Mean emotional functioning for those with a threshold mood, anxiety and/or adjustment disorder was almost a full standard deviation (17.5 points) lower than for those who were interviewed and did not meet the criteria for either a threshold or subthreshold diagnosis (p < 0.001). Hispanic ethnicity was borderline significant (6 point increase, p=0.075). Only transplant center and Axis-I diagnosis were retained in the multivariable model (Table 4).
Table 2.
Descriptive statistics for baseline variables (N=165)
| Mean (SD), median (25th to 75th), or n (%) |
|
|---|---|
| Parent Characteristics | |
| Parent age in years, mean (SD) | 38.9 (6.9) |
| Parent gender, n (%) | |
| Female | 139 (84.2%) |
| Male | 26 (15.8%) |
| Parent race, n (%) | |
| White | 133 (83.1%) |
| Black or African American | 7 (4.4%) |
| Asian | 4 (2.5%) |
| Native Hawaiian/Pacific Islander | 3 (1.9%) |
| American Indian/Alaska Native | 6 (3.8%) |
| Other, Refused, Mixed | 7 (4.4%) |
| Parent ethnicity, n (%) | |
| Non-Hispanic | 129 (79.1%) |
| Hispanic | 34 (20.9%) |
| Parent education, n (%) | |
| Less than high school | 13 (7.9%) |
| High school graduate | 45 (27.3%) |
| Some college | 47 (28.5%) |
| College or more | 60 (36.4%) |
| Parental Axis-I diagnosis, n (%) | |
| No | 49 (29.7%) |
| Subthreshold | 20 (12.1%) |
| Threshold | 34 (20.6%) |
| Not done or inevaluable | 62 (37.6%) |
| Child Characteristics | |
| Child age in years, mean (SD) | 10.8 (3.9) |
| Child gender, n (%) | |
| Female | 82 (49.7%) |
| Male | 83 (50.3%) |
| Number of siblings, n (%) | |
| None | 14 (8.5%) |
| One | 60 (36.4%) |
| Two or more | 91 (55.2%) |
| Causal malignancy, n (%) | |
| Yes | 141 (85.5%) |
| No | 24 (14.6%) |
| Transplant type, n (%) | |
| Autologous | 32 (19.4%) |
| Related allogenic | 51 (30.9%) |
| Unrelated allogenic | 82 (49.7%) |
| Duration of illness in months, median (25th to 75th) | 10.0 (5.0, 31.0) |
| Prior Treatment, n (%) | |
| Yes | 125 (75.8%) |
| No | 40 (24.2%) |
| Timing of baseline measures, n (%) | |
| Before preparative regimen | 69 (41.8%) |
| During preparative regimen | 96 (58.2%) |
| Transplant center, n (%) | |
| Center 1 | 65 (39.4%) |
| Center 2 | 21 (12.7%) |
| Center 3 | 29 (17.6%) |
| Center 4 | 28 (17.0%) |
| Center 5 | 4 (2.4%) |
| Center 6 | 18 (10.9%) |
Notes: 5 missing race, 2 missing parent ethnicity.
The mean time of Axis-I diagnosis relative to the transplant date was -2.5 days (SD, 7.3 days).
Of the 62 Axis-I interviews “not done or inevaluable,” 5 interviews were inevaluable.
Fifty-seven subjects declined to be interviewed.
Table 3.
Univariate analyses of relation between parent emotional functioning at baseline and baseline variables (N=165)
| Mean baseline parent emotional functioning (SD)* or β (SE)** | p-value | |
|---|---|---|
| Parent Characteristics | ||
| Parent age in years, β (SE) | 0.14 (0.22) | 0.528 |
| Parent gender, mean (SD) | 0.168 | |
| Female | 48.6 (18.7) | |
| Male | 54.0 (17.2) | |
| Parent race, mean (SD) | 0.184 | |
| White | 48.6 (17.6) | |
| Black or African American | 63.9 (19.7) | |
| Asian | 38.5 (7.9) | |
| Native Hawaiian/Pacific Islander | 59.7 (2.4) | |
| American Indian/Alaska Native | 45.8 (24.9) | |
| Other, Refused, Mixed | 51.8 (23.8) | |
| Parent ethnicity, mean (SD) | 0.075 | |
| Non-Hispanic | 48.1 (17.3) | |
| Hispanic | 54.4 (21.9) | |
| Parent education, mean (SD) | 0.671 | |
| Less than high school | 48.4 (19.9) | |
| High school graduate | 46.7 (14.5) | |
| Some college | 51.2 (19.6) | |
| College or more | 50.2 (20.1) | |
| Parent Axis-I diagnosis, mean (SD) | <0.001 | |
| No | 55.0 (15.3) | |
| Subthreshold | 52.5 (17.5) | |
| Threshold | 37.5 (14.5) | |
| Not done or inevaluable | 50.5 (20.5) | |
| Child Characteristics | ||
| Child age in years, β (SE) | 0.22 (0.37) | 0.549 |
| Child gender, mean (SD) | 0.293 | |
| Female | 47.9 (18.3) | |
| Male | 50.9 (18.7) | |
| Number of siblings, mean (SD) | 0.781 | |
| None | 49.1 (15.4) | |
| One | 48.1 (18.2) | |
| Two or more | 50.3 (19.2) | |
| Causal malignancy, mean (SD) | 0.975 | |
| Yes | 49.4 (18.7) | |
| No | 49.3 (17.5) | |
| Transplant type, mean (SD) | 0.930 | |
| Autologous | 49.4 (20.8) | |
| Related allogenic | 48.6 (20.5) | |
| Unrelated allogenic | 49.9 (16.3) | |
| Log duration of illness in months, β (SE) | 1.0 (1.2) | 0.441 |
| Prior treatment, mean (SD) | 0.489 | |
| Yes | 50.0 (19.0) | |
| No | 47.6 (16.8) | |
| Timing of baseline measures, mean (SD) | 0.569 | |
| Before preparative regimen | 48.4 (18.7) | |
| During preparative regimen | 50.1 (18.4) | |
| Transplant center, mean (SD) | 0.012 | |
| Center 1 | 44.4 (17.1) | |
| Center 2 | 46.3 (16.2) | |
| Center 3 | 58.0 (19.8) | |
| Center 4 | 51.6 (19.6) | |
| Center 5 | 43.8 (13.0) | |
| Center 6 | 55.3 (17.8) | |
Notes:
Higher scores correspond to higher functioning
Mean (SD) displayed for binary or categorical variables
Beta coefficient (SE) displayed for continuous variables
p-value from: t-test (binary), ANOVA (categorical), or linear regression (continuous)
Table 4.
Multivariable baseline model (N=165)
| β (SE) | p-value | |
|---|---|---|
| Intercept | 50.0 (2.9) | <0.0001 |
| Transplant center, n (%) | ||
| Center 1 | reference | |
| Center 2 | 6.5 (4.5) | 0.149 |
| Center 3 | 16.1 (4.3) | <0.001 |
| Center 4 | 9.9 (3.9) | 0.011 |
| Center 5 | -1.7 (8.8) | 0.848 |
| Center 6 | 10.8 (4.6) | 0.020 |
| Parental Axis-I diagnosis | ||
| No | reference | |
| Subthreshold | 0.1 (4.7) | 0.982 |
| Threshold | -17.7 (3.9) | <0.001 |
| Not done or inevaluable | -9.0 (3.6) | 0.014 |
Global p-value for transplant center: p=0.002 and parental Axis-I diagnosis p=0.001
Longitudinal Analysis
Early Complications
Complication frequencies are in Table 5. AGVHD grade ≥ 2, intermediate or poor organ toxicity, and systemic infection were associated with decreases in mean parental emotional functioning of 5.2 (p=0.09), 5.8 (p=0.05), and 5.1 (p=0.02) points, respectively, after adjustment for time period and the parent's emotional functioning at baseline (Table 6). This represents about a quarter to a third of a standard deviation difference. The parent's emotional functioning at baseline was the only baseline variable retained in the models. Of note, transplant type and disease diagnosis were not significant (p=0.63 and 0.14). Emotional functioning for parents of children with the early composite was 6.1 points lower (p=0.01) than for those without complications (Table 6), which approximates 1/3 of a standard deviation of parental emotional functioning, a clinically important difference.
Table 5.
Complications (frequency and percent)
| 45 days | 3 months | 6 months | 12 months | |
|---|---|---|---|---|
| Early Complications | n=139 | n=125 | ||
| aGVHD, n (%) | ||||
| Autologous1 | 24 (17.3%) | 24 (19.2%) | ||
| None, grade 1 | 95 (68.3%) | 83 (66.4%) | ||
| ≥ grade 2 | 20 (14.4%) | 18 (14.4%) | ||
| Bearman toxicity, n (%) | ||||
| Good | 112 (80.6%) | 100 (80.0%) | ||
| Intermediate/poor | 27 (19.4%) | 25 (20.0%) | ||
| Infection, n (%) | ||||
| None | 93 (67.4%) | 80 (64.5%) | ||
| Localized | 7 (5.1%) | 15 (12.1%) | ||
| Systemic | 38 (27.5%) | 29 (23.4%) | ||
| Unplanned subsequent transplant, n (%) | ||||
| No | 139 (100.0%) | 124 (99.2%) | ||
| Yes | 0 (0.0%) | 1 (0.8%) | ||
| Early complications composite, n (%) | ||||
| No | 97 (69.8%) | 89 (71.2%) | ||
| Yes | 42 (30.2%) | 36 (28.8%) | ||
| Late Complications | n=123 | n=109 | ||
| cGVHD, n (%) | ||||
| Autologous1 | 25 (20.3%) | 21 (19.3%) | ||
| None | 57 (46.3%) | 44 (40.4%) | ||
| Limited | 22 (17.9%) | 30 (27.5%) | ||
| Extensive | 19 (15.4%) | 13 (11.9%) | ||
| Infection, n (%) | ||||
| None | 100 (82.0%) | 90 (84.1%) | ||
| Localized | 9 (7.4%) | 11 (10.3%) | ||
| Systemic | 13 (10.7%) | 6 (5.6%) | ||
Patients with autologous transplants are not eligible for GVHD and were therefore excluded from the GVHD models.
Abbreviations: aGVHD= acute graft versus host disease; cGVHD=chronic graft versus host disease
Early composite: aGVHD>=grade 2, Bearman>=intermediate, infection=systemic, unplanned subsequent transplant within 100 days
Not tabulated because outcome missing: 1 infection at 45 days; 1 infection at 3 months; 1 infection at 6 months; 1 cGVHD at 12 months; 2 infection at 12 months
At 3 months, 8 subjects had limited and 3 had extensive cGVHD. These were included in a model covering the 3, 6, and 12 month time points (data not shown).
Table 6.
Relation between HSCT complications and parent's emotional functioning.
| β (SE) | p-value | |
|---|---|---|
| Early (45 days and 3 months) | ||
| Model 1: aGVHD | ||
| Intercept | 32.0 (3.7) | <0.0001 |
| 45 days | reference | |
| 3 months | -1.6 (1.4) | 0.258 |
| aGVHD | ||
| None, grade 1 | reference | |
| ≥ grade 2 | -5.2 (3.0) | 0.086 |
| Baseline parent emotional functioning | 0.5 (0.1) | <0.0001 |
| Model 2: Bearman | ||
| Intercept | 31.9 (3.6) | <0.0001 |
| 45 days | reference | |
| 3 months | -1.4 (1.4) | 0.317 |
| Bearman | ||
| Good | reference | |
| Intermediate/poor | -5.8 (3.0) | 0.052 |
| Baseline parent emotional functioning | 0.5 (0.1) | <0.0001 |
| Model 3: Infection | ||
| Intercept | 31.7 (3.7) | <0.0001 |
| 45 days | reference | |
| 3 months | -1.3 (1.4) | 0.363 |
| Infection* | ||
| None | reference | |
| Localized | -2.8 (3.5) | 0.430 |
| Systemic | -5.1 (2.2) | 0.023 |
| Baseline parent emotional functioning | 0.5 (0.1) | <0.0001 |
| Model 4: Early Composite | ||
| Intercept | 33.1 (3.7) | <0.0001 |
| 45 days | reference | |
| 3 months | -1.6 (1.4) | 0.263 |
| Early composite | ||
| No | reference | |
| Yes | -6.1 (2.4) | 0.013 |
| Baseline parent emotional functioning | 0.5 (0.1) | <0.0001 |
| Late (6 and 12 months) | ||
| Model 5: cGVHD | ||
| Intercept | 34.9 (4.2) | <0.0001 |
| 6 months | reference | |
| 12 months | 6.0 (1.8) | 0.001 |
| cGVHD** | ||
| None | reference | |
| Limited | 0.7 (3.3) | 0.824 |
| Extensive | 2.5 (4.0) | 0.534 |
| Baseline parent emotional functioning | 0.5 (0.1) | <0.0001 |
| Model 6: Infection | ||
| Intercept | 36.2 (3.9) | <0.0001 |
| 6 months | reference | |
| 12 months | 5.3 (1.6) | 0.002 |
| Infection* | ||
| None | reference | |
| Localized | 3.2 (3.6) | 0.364 |
| Systemic | -20.2 (3.9) | <0.0001 |
| Baseline parent emotional functioning | 0.5 (0.1) | <0.0001 |
global p-values for infection: p = 0.072 early; p < 0.0001 late
global p-value for cGVHD: 0.823
Late Complications
Complication frequencies are in Table 5. In analyses adjusted for time period and the parent's emotional functioning at baseline, infection was significantly associated with the outcome. Emotional functioning for parents of children with systemic infection was 20.2 points lower than that for parents of children with no infection (p < 0.0001, Table 6). CGVHD was not significantly associated with the outcome.
Discussion
Prior studies have established that parental stress is highest prior to transplant and during the transplant hospitalization, decreasing steadily thereafter [5, 17, 18]. These studies revealed that parents with high levels of stress during the acute phase of HSCT were most at risk in the long term. Our data confirm these findings, but also reveal that the trajectory of parental emotional functioning is more nuanced than previously understood. Specifically, we found that recovery of parental emotional functioning was impeded by clinical complications of HSCT, including aGVHD, organ toxicity, and early-onset infection.
We also found that systemic infection later in the post-HSCT period, at 6 and 12 months, had a strong association with parental emotional functioning, whereas cGVHD did not. Since the numbers with systemic infection at 6 and 12 months were low, the estimated impact of infection may have been exaggerated by a few unusual cases. The strong association between late-onset systemic infection and parental emotional functioning may be explained by the unexpected nature of such infections, the need to return to the hospital, and the experiencing anew of the disruption of hospitalization. Anecdotally, some parents have reported that they “thought they were done,” with this once they had passed the acute transplant period. These explanations, although speculative, may also underlie our failure to detect an association with cGVHD. CGVHD typically does not require emergency rehospitalization and while it represents a serious complication of transplant, it is not completely unexpected, particularly for those with a prior history of aGVHD.
Although our sample size is among the largest in studies of this population, the number of patients who experienced each of the early complications was limited. Defining a composite variable for early complications increased statistical power and was justified by the similar effects of the components on the outcome. Specifically, grade 2 or higher aGVHD, intermediate or poor maximum Bearman toxicity, and systemic infection were each associated with a five to six point decrement in parental emotional functioning.
Since the parent's emotional functioning at baseline was strongly predictive of their emotional functioning at later time points (each one point difference at baseline predicted a half point difference at the other time points, p < 0.0001), we performed analyses to assess the determinants of baseline emotional functioning. Among the demographic, clinical, and transplant-related variables we tested, only Axis-I diagnosis and transplant center were statistically significant in univariate and multivariable analyses. In earlier analyses, the timing of the baseline assessment was found to be strongly associated with the parent's ratings of the child's functioning, such that parents who filled out the questionnaires during the preparative regimen rated the children's functioning significantly lower on average than those who filled it out before the regimen began [6]. Thus we were surprised that baseline timing was not associated with parents’ ratings of their own emotional functioning. Perhaps this was due to their already high levels of distress, as reported in previous studies during the pre-transplant period [19-21].
Previous research has demonstrated that parenting stress can be high in the post-transplant period for a subset of parents [22]. The collateral impact of the transplant process on parent caregivers [23] may influence their reporting of the child's status. Higher levels of parental stress have been shown to be predictive of poor parental ratings of the child's HRQL[5, 8]. As post-transplant care increasingly shifts away from the transplant center to the local provider and to home-based care, it is imperative that the needs of the parent caregivers are recognized and adequately addressed to ensure their optimum functioning and that of the child, particularly in light of reported associations between high parental stress and child distress[2].
Our results demonstrate that transplant center was a statistically significant factor in both univariate and multivariate analysis. Although we cannot definitively explain these findings, they may be related to two possible issues. First, transplant centers vary considerably in their requirements and expectations of families as they embark on the transplant process. At one end of the spectrum, some centers require that families arrive at least two weeks before the scheduled admission. All pre-transplant testing and orientation to transplant are performed at the transplant center. At other centers, families are allowed to arrive essentially the day of admission, bringing with them data from the pre-transplant evaluation. We suspect that parental stress may vary considerably by these different arrangements. Second, although the centers participating in the study offered the full array of transplant options (by conditioning regimen, transplant type, and progenitor source), there may be undetectable differences with respect to diagnosis. Diagnostic mix may influence parental emotional functioning due to prognosis, duration of illness, fear of recurrence, and other factors.
Our results have implications for future intervention. Specifically, parents who report high levels of stress at the time of transplant may warrant formal referral to mental health providers and/or direct interventions to teach parents stress-reduction techniques, as described by Streisand et al.[21] and more recently, by Warner and co-workers [24]. Moreover, the strong association we found between parental emotional functioning and clinical complications during the post transplant period suggests that these clinical complications may serve as important sentinel events, triggering increased parental distress, which in turn, may require direct intervention and/or referral.
Future research is needed to integrate our findings on the impact of clinical complications with other studies, which have highlighted important psychosocial factors associated with parental distress [22]. This combination of factors may help to target at risk parents, which in turn could lead to more timely intervention.
In conclusion, we studied parents of children recovering from HSCT and found that complications of the child's treatment during the first year post-transplant were associated with decrements in the parent's emotional functioning.
Acknowledgments
Funding: Supported by American Cancer Society grant RSGPB-02-186-01-PBP (Parsons, PI) and NIH grant R01 CA119196 (Parsons, PI)
Appendix 1
Bearman Maximum overall toxicity
Regimen-related, non-hematologic toxicity during the first 100 days following HSCT was evaluated for all patients using the Bearman Toxicity Scale, which is widely used in HSCT-related clinical studies. [15] The scale utilizes a four-point scale from 0-3, (range, absent to severe, end-organ damage) for each of eight organ systems (e.g., cardiac, bladder, renal, pulmonary, hepatic, CNS (central nervous system), stomatitis, and GI (gastrointestinal). Maximum overall toxicity is classified as ‘good,’ ‘intermediate,’ or ‘poor,’ based on the combination of toxicity grading for each organ system. ‘Good’ is defined as ≤ grade 1 in all organ systems or maximum toxicity of 2 in ≤ 2 organ systems. ‘Intermediate’ is defined as maximum toxicity of 2 in ≥ 3 organ systems, and ‘poor’ is defined as maximum toxicity of 3 in at least one organ system.
Appendix 2
PARTICIPATING INSTITUTIONS AND SITE INVESTIGATORS IN THE JOURNEYS TO RECOVERY STUDY
Central Project Staff
Tufts Medical Center, Boston, MA: Susan K. Parsons, MD, MRP, Principal Investigator
Site Principal Investigators
Baylor College of Medicine/Texas Children's Hospital, Houston, TX: Lynette Harris, PhD and Robert A. Krance, MD, Principal Investigators
City of Hope, Duarte, CA: Sunita Patel, PhD, Principal Investigator; Joseph Rosenthal, MD, Site Consultant
Dana-Farber Cancer Institute, Boston, MA: Christopher Recklitis, PhD, MPH, Principal Investigator
Fred Hutchinson Cancer Research Center, Seattle, WA: Karen L. Syrjala, PhD, Principal Investigator; Jean Sanders, MD, Co-Principal Investigator
Medical College of Wisconsin, Milwaukee, WI: Mary Jo Kupst, PhD, Principal Investigator; Kristin Bingen, PhD and James Casper, MD, Co-Principal Investigators
University of Pittsburgh/Children's Hospital of Pittsburgh, Pittsburgh, PA: Robert B. Noll, PhD, Principal Investigator; Linda J. Ewing, PhD, RN, Co-Principal Investigator
Footnotes
Note to the editor: We have no conflicts of interest to declare. We have full control of all primary data and agree to allow the journal to review the data if requested.
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