Cognitive, educational, psychosocial adjustment and quality of life of ...

Bone Marrow Transplantation (2008) 42, 15–21 & 2008 Macmillan Publishers Limited All rights reserved 0268-3369/08 $30.00

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ORIGINAL ARTICLE

Cognitive, educational, psychosocial adjustment and quality of life of children who survive hematopoietic SCT and their siblings M Barrera and E Atenafu Department of Psychology, Population Health Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada

Our objective was to compare cognitive, educational and psychosocial outcomes, and quality of life (QOL) of pediatric hematopoietic SCT (HSCT) survivors with those of their siblings, 2 years post-HSCT. Forty-six HSCT survivors, with age ranging from 3 to 16 years, and 33 siblings, with age ranging from 3 to 20 years, participated. Standardized tests were performed and questionnaires were completed by the participating children and their mothers. Survivors’ full, verbal and performance IQ scores did not differ significantly from those of their siblings. Survivors, however, had significantly higher perceptual organization scores than their siblings. Siblings’ mean scores on spelling were significantly higher than those of survivors, but arithmetic and reading scores were not. Siblings had significantly more internalizing problems than survivors. Siblings’ physical QOL scores were significantly better than those of survivors. Finally, child age, maternal depression scores and age, and family cohesion were related to cognitive and educational differences. A history of cranial radiation and a diagnosis of neuroblastoma or Hodgkin’s lymphoma in survivors were related to the difference in internalizing scores. Except for some deficits in educational outcomes and physical QOL, survivors’ cognitive and psychological outcomes at 2 years post-HSCT were similar to those of their siblings. Family and clinical factors were identified as critical for these outcomes. Bone Marrow Transplantation (2008) 42, 15–21; doi:10.1038/bmt.2008.84; published online 31 March 2008 Keywords: cognitive; educational; psychosocial outcomes; children; HSCT

Introduction Children and adolescents who undergo hematopoietic SCT (HSCT) may be vulnerable to cognitive, educational,

Correspondence: Dr M Barrera, Department of Psychology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8. E-mail: [email protected] Received 16 October 2007; revised 8 February 2008; accepted 18 February 2008; published online 31 March 2008

perceptual motor skills and psychosocial deficits resulting from the treatment and disease. Although early retrospective studies have reported cognitive and academic deficits in survivors of pediatric BMT, particularly if they received cranial radiation at a younger age,1,2 more recent prospective studies have found that, in general, survivors of HSCT perform well, cognitively and educationally, or even improve some of their performance 2 years post-HSCT compared with their pre-HSCT performance.3,4 Moreover, some child characteristics (older age at transplant) and familial factors (older maternal age and less maternal depression symptoms) seem to be associated with better outcomes.3 It is less clear how survivors’ outcomes compare to those of their healthy siblings, who are exposed to the family crisis precipitated by the diagnosis of a lifethreatening illness such as cancer, the intense treatment that culminates in a transplant and related complications. This study addresses this gap. Survivors of childhood cancer have been compared with their close-in-age siblings in cognitive, educational, quality of life (QOL) and psychosocial outcomes with variable results. Indeed, some studies have found that survivors have more cognitive and educational deficits than their siblings.5–9 Other studies have found no differences between survivors of childhood cancer and their healthy siblings in behavioral, educational and social problems, as well as feelings of distress, guilt and psychosomatic symptoms.10–13 In contrast, in an early study, siblings of childhood cancer survivors showed more distress than the survivors in perceived social isolation;11 or survivors performed like their siblings in psychological adjustment but did significantly worse than their siblings in educational outcomes.14 A recent study examining post-traumatic stress found that siblings reported more symptoms of post-traumatic stress than did childhood cancer survivors.10 In another recent study, siblings and survivors of leukemia did not differ in behavioral problems but siblings displayed more social and academic difficulties.12 Finally, in a late-effects study of psychosocial and QOL outcomes, survivors, in general, reported worse outcomes than their siblings.15 Clearly, the current inconclusive evidence comparing children with cancer with their siblings provides little direction as to whether survivors of HSCT will be worse off than their siblings. To date, to our knowledge, there are no published studies that compare the comprehensive outcomes of pediatric

Cognitive, educational and psychosocial outcomes of HSCT-treated children M Barrera and E Atenafu

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HSCT survivors with those of their siblings. The only comparative study of siblings in this population examined the psychosocial outcomes of donor and non-donor siblings of children who undergo HSCT, but did not compare them with the ill child. Donors were reported to have significantly more anxiety than non-donors but nondonors were reported to have more problems at school.16 HSCT inflicts added stress on children and families already over-burdened with a wide range of medical, psychosocial and financial stresses related to the diagnosis of cancer or other blood disorders and unsuccessful treatment. Considering this and the aggressiveness of the HSCT procedure, one may expect that the outcomes for survivors and siblings may be worse than the outcomes for childhood cancer survivors who do not undergo an HSCT. Augmenting the knowledge of the long-term cognitive, educational, psychosocial and overall QOL outcomes of survivors will help clinicians and families to make decisions regarding comprehensive care and future planning. Thus, the main objective of this study was to compare cognitive, educational, perceptual motor skills, and psychosocial outcomes and QOL of HSCT survivors with their close-in-age siblings at 2 years post-HSCT. The secondary objective was to examine clinical, familial and child factors that may be associated with the differences, if any, between the groups. To examine related factors, we used a conceptual model to explore the potential factors that could explain any of the differences between the outcomes for survivors and siblings, which was similar to that used in earlier studies of children who were diagnosed with cancer,17 their parents18 and the longitudinal sample of survivors of HSCT.3 Briefly, this multivariable model proposes that individual psychological outcomes after a major health crisis, such as undergoing HSCT, will be influenced by personal (e.g., age and gender), clinical (e.g., diagnosis, time since diagnosis and conditioning protocol) and familial factors. Given the added medical demands for the ill child with this procedure and the great deal of attention they receive, we predicted that survivors will show better psychosocial outcomes than their siblings, but will still show deficits in cognitive and educational outcomes and physical QOL. Given our previous findings that familial factors contributed to the survivors’ cognitive and educational outcomes,3 and that both survivors and siblings have different experiences within the same family, it is likely that, when differences exist, familial factors such as maternal depression scores will be associated with poorer outcomes in survivors. This study was part of a major project investigating the psychosocial and educational outcomes in a family after pediatric HSCT.

Materials and methods Participants and recruitment Potential survivor participants for this investigation were children over the age of 3 years who participated in the longitudinal study of the larger project and had complete data at 2 years post-HSCT. All the families that had eligible siblings agreed to participate in the longitudinal study but Bone Marrow Transplantation

not all ill children survived 2 years post-HSCT. Complete data were obtained for 46 survivors and 33 siblings. The inclusion criteria for siblings were as follows: age within 2 years of the target child’s age and presenting with no major health problems. Only one sibling per family participated and five of the siblings were donors. Comparisons related to being a donor, however, were not the focus of this investigation. Table 1 presents clinical and demographic characteristics of the survivors and siblings. Briefly, mean age of participating survivors was 10.13 years (s.d. ¼ 4.4, range 3–16), whereas that of siblings was 10.96 years (s.d. ¼ 3.82, range 3–20). Majority of survivors were diagnosed with other leukemia types (i.e., AML and CML), neuroblastoma and ALL. Other diagnoses included hematological disorders and Hodgkin’s lymphoma. The majority of survivors (68%) underwent an allogeneic transplant (48% related). Seventy-four percent experienced no cranial radiation before or during conditioning. The mean time since diagnosis at pre-HSCT was 19.9 months (s.d. ¼ 19.5). Most children came from a two-parent European-descent family and a middle-class socio-economic background.19 The majority of parents had undergone at least part of college or university education.

Procedure After approval from the Research Ethics Board was obtained, an invitation letter was sent to all eligible families describing the study and inviting them to participate in the study, with the last assessment at 2 years post-transplant. Informed consent and assent were obtained at the initial assessment for the survivors. Assent or consent of siblings was obtained at their participation 2 years post-HSCT. Families were scheduled for two assessment sessions, one for the sibling and one for the survivor, to complete the cognitive, educational and visual motor performance tests and behavioral questionnaires. The mother was the primary parent during the HSCT and the one who completed the questionnaires about the survivor’s and sibling’s behavior and QOL, and about her own as well. Outcome measures General Intelligence was measured using the Wechsler Intelligence Scale for Children Third Edition20 (WISC-III). The Wechsler scales are well normed, producing IQ estimates labeled as verbal (VIQ; which includes information, similarities, arithmetic, vocabulary and comprehension subtests), performance (PIQ; which includes picture completion, coding, picture arrangement, block design and object assembly) and full scale (FIQ). Using the WISC-III subtests, including two supplementary subtests (digit span and symbol search), we derived specific factor-based cognitive indices: freedom from distractibility (which includes arithmetic and digit span), processing speed (which includes coding and symbol search) and perceptual organization (PO; which includes picture completion, picture arrangement, block design and object assembly) and verbal comprehension (which includes all the subtests of the verbal scale except arithmetic and digit span). The latter index was not used because it tests basically the same constructs as VIQ. Average reliability estimates for the IQ


17 Table 1 Clinical and familial characteristics of survivors of HSCT and their siblings Factor

Age (years) Maternal age at HSCT

Survivors (46)

Siblings (33)

Mean

(s.d.)

Mean

(s.d.)

10.13 36.41

(4.37) (5.64)

10.96

(3.82)

N

% value

N

% value

Gender Female Male

20 26

43.5 56.5

11 23

32.3 67.7

Diagnosis ALL Other leukemia types Neuroblastoma Hodgkin’s lymphoma Hematologic disorders

8 12 14 4 8

17 26 30 9 17

— — — — —

— — — — —

Time since diagnosis (months) o30 30–36 436

15 16 15

32.6 34.8 32.6

— — —

— — —

Type of transplant Allogeneic Related Unrelated Autologous

38 22 16 8

83 48 35 17

— — — —

— — — —

Radiation history No radiation TBR only CRT and TBR

32 10 4

74 22 9

— — —

— — —

Radiation group (cGy) o300 4+1200

35 11

76 24

— —

— —

Maternal education Part of high school Complete high school Part of college/university Complete college/university

3 8 12 23

6 17 26 50

— — — —

— — — —

Abbreviations: CRT ¼ cranial radiation therapy; HSCT ¼ hematopoietic SCT; TBR ¼ total body radiation.

measures range from 0.91 to 0.96. The Wide Range Achievement Test21 assesses educational achievement, such as reading, spelling and arithmetic skills. Reliability estimates range from 0.92 to 0.95. Participants also completed the Developmental Test of Visual Motor Integration (VMI-4), a measure that assesses visual motor skills in children from 3 to 18 years of age.22 The overall reliabilities for this measure are 0.92 for the total VMI, 0.91 for the visual test and 0.89 for the motor test. Although these scales have been revised since we started the first cohort of this study over 7 years ago, we continued to use the older versions to maintain consistency with the longitudinal scores.3 The Child Behavior Checklist (CBCL) for ages 4–18 years is a parent-completed questionnaire23 and was used to assess psychosocial adjustment. It consists of 112 items,

which assess the extent to which a child exhibits common problem behaviors. This measure also provides information about the child’s social competence. Ratings are summed to obtain total, internalizing (symptoms of anxiety, depression and withdrawal) and externalizing (symptoms of aggression) scores for the behavioral scale and a total social competence score. All three scales had good test–retest reliability (r ¼ 0.89, 0.93 and 0.93, respectively) and adequate validity.24 For this study, we used internalizing and externalizing T-scores. The Child Health Questionnaire25 50-item parent-report version (CHQ-PF50) was used to assess QOL. The CHQPF50 is a generic, well-validated measure designed for use across diverse groups of children with various health conditions. It provides two summary scores, physical and psychosocial health, and several subscales including physical function, general behavior, mental health, physical pain, self-esteem and general health. Both summary scores were used in this study. All scales were constructed and scored using Likert’s scale using a 4-week recall period, except for general health where no recall period is used. Higher scores indicate better functioning and well-being.

Measures of related factors The Family Adaptability and Cohesion Evaluation Scale26 (FACES-III) and the Beck Depression Inventory27 (BDI) were used as the measures of family cohesion and maternal distress, respectively, as potential related factors. These measures were chosen because they are brief and widely used in families with a history of childhood chronic illness or cancer and could be completed by a parent with minimal burden. FACES-III is a 20-item scale with two dimensions of family relations: adaptation and cohesion. Test–retest reliability over a 4- to 5-week period was r ¼ 0.80 for adaptability, and r ¼ 0.83 for cohesion, with high discriminative validity.28 In this study, the cohesion score was used as a measure of family functioning. The BDI is a selfadministered 21-item questionnaire designed to measure depressive symptomatology. The BDI has been found to be highly sensitive in measuring changes in depressive symptoms and severity.29 Concurrent validity of the BDI with most other self-report measures of depression has been consistently high.29 Both measures were completed by the mother. Clinical and demographic factors. Information on the child’s disease and treatment was obtained from the medical chart and confirmed by parental report. The clinical variables considered in this study were as follows: diagnosis type (ALL, other leukemias, neuroblastoma, Hodgkin’s lymphoma and hematological disorders), time since diagnosis (stratified into less than 30, between 30 and 36, and more than 36 months), history of radiation treatment (no radiation, total body radiation (TBR) only, and combined cranial radiation therapy (CRT) and TBR) and radiation group (o300 cGy or 41200 cGy). The child characteristics included in this study were as follows: child’s age at pre-HSCT and gender. Maternal age and education were also considered, with the latter as an index of socioeconomic status. Bone Marrow Transplantation


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Statistical analysis Initially, descriptive statistics were calculated for the outcome measures and related variables. Because of the small sample size and missing data for some of the variables (see Table 2), all the outcome measures were tested for normalcy using the Kolmagorov–Smirnov test. The majority of the variables did not violate the assumption of normalcy. However, because the FIQ and VIQ scores were not normally distributed, they were tested using both parametric and non-parametric tests in the comparisons between survivors and siblings. These results were similar, hence only the parametric results are reported. Paired t-tests were conducted to compare survivor and sibling scores on all measures (cognitive, visual motor, educational, psychosocial and QOL). When there was a significant difference between survivors and siblings, we examined what factors may have accounted for the difference. Thus, the following analyses were conducted to select and reduce potential predictors of differences. To avoid collinearity, a pair-wise assessment of associations between predictors was examined. That is, w2-tests within categorical predictors, analysis of variance for continuous and categorical and Pearson correlations for continuous variables were conducted. The variables found to have high potential collinearity were not included together in a multivariable model. Covariates significant at the 20% level in the bivariate analyses were included in the full multivariable, generalized linear regression model. History of radiation was chosen over radiation group based on these preliminary analyses. Generalized linear regression models were then constructed to examine the effects of the potential factors associated with the differences between survivors and siblings. These analyses were conducted using SAS software version 9.1 (SAS Institute Inc., Cary, NC, USA).

Table 2 Means and s.d. for outcome and related measures of survivors of HSCT and their siblings

Results

reading were in the same direction but did not reach significance.

Differences in outcome measures between survivors and siblings Table 2 presents the means and s.d. of the outcome measures for survivors and their siblings, as well as the related factors.

Factor

Survivors N

Intelligence scales (IQ) Full Verbal Performance

Mean

46 105.69 46 100.21 46 110.92

Cognitive indices Freedom from distraction 46 98.19 Perceptual organization 46 97.57 Processing speed 32 108.97 Visual motor integration

Siblings

(s.d.)

N

Mean

(s.d.)

16.40 33 103.97 14.26 16.38 33 100.45 12.99 17.77 33 107.45 16.13

15.51 33 99.73 3.56 11.36 33 94.41 11.80* 16.25 32 107.38 13.76

44

94.07

12.69 31

99.94 16.15

Academic (WRAT) Spelling Reading Arithmetic

41 42 42

97.71 98.57 92.76

16.35 26 105.00 15.08* 15.48 26 103.03 17.91 13.23 26 96.52 11.06

Child behavior (CBCL) Total Internalizing Externalizing

46 46 46

47.46 47.17 47.72

10.44 34 10.40 34 9.53 34

49.51 11.94 51.17 10.19* 49.43 10.09

QOL Physical Psychosocial

42 42

46.65 52.88

12.12 32 9.57 31

57.04 53.20

3.63** 8.53

Family factors Maternal depression Family cohesion

46 15

4.10 1.39

4.62 — 0.49 —

— —

— —

Abbreviations: CBCL ¼ Child Behavior Checklist; HSCT ¼ hematopoietic SCT; QOL ¼ quality of life; WRAT ¼ Wide Range Achievement Test. *Po0.05. **Po0.001.

Psychological adjustment. The mean score for total CBCL, and externalizing scores, did not differ significantly between survivors and siblings but the difference between their mean internalizing scores was significant, with the siblings scoring 4 points higher than the survivors, suggesting more internalizing problems (t(32) ¼ 2.66, Po0.02). However, as a group, the mean internalizing score for survivors and siblings were within the normal range.

Cognitive and visual motor outcomes. Mean FIQ, PIQ and VIQ scores of survivors did not differ significantly from the corresponding mean scores of their siblings. Although survivors’ mean PIQ scores were higher than those of their siblings, this difference did not reach significance (t(31) ¼ 1.70, P ¼ 0.10). Analysis of the cognitive indices indicated that the mean for PO was significantly higher for survivors than the mean for siblings (t(31) ¼ 2.14, P ¼ 0.04). Both PO scores, however, were within the normal range. Moreover, the VMI mean standard scores for survivors and siblings did not differ significantly.

Quality of life. The mean physical QOL summary score for survivors was significantly below the mean for siblings, suggesting more physical difficulties in survivors 2 years post-HSCT (t(51) ¼ 4.51, Po0.0001), with a difference of 10 points. The mean psychosocial QOL summary scores did not differ significantly between the groups.

Educational outcomes. Siblings’ mean scores for spelling were significantly higher than those of survivors (t(25) ¼ 2.06, Po0.05), with the siblings’ scores being more than 7 points higher. The mean scores for arithmetic and

Factors associated with the differences between survivors and siblings To further understand the differences found between the survivors and siblings in the cognitive index of PO, the

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educational outcome, spelling, psychological adjustment, measured by internalizing scores, and physical QOL, next we examined potential clinical factors (diagnosis, history of radiation, time since diagnosis, type of transplant), child characteristics (age) and family factors (maternal age and depression scores, family cohesion) that might be related to these differences. Preliminary analyses indicated that none of the clinical variables were associated with the difference between siblings and survivors in PO, which reflected better scores for the survivors than the siblings. Two familial factors, maternal age and family cohesion, were identified in preliminary analyses, using parametric and nonparametric statistics, as associated with the difference between the groups in PO and included in the regression model. The model was significant (R2 ¼ 0.60, F(2,14) ¼ 9.30, P ¼ 0.0036), with maternal age (F(1,14) ¼ 13.79, P ¼ 0.02) and family cohesion (F(1,14) ¼ 8.92, P ¼ 0.011) being associated to the difference, in spite of the small sample that had family cohesion data. These results indicate that the older the mothers, the higher the differences in favor of the survivor. Moreover, the difference was greater in more cohesive families. For the difference in spelling, which reflected better outcomes for siblings than for survivors, the regression model (R2 ¼ 0.47, F(2,22) ¼ 9.83, Po0.0001) included two factors: child age (F(1,22) ¼ 8.76, P ¼ 0.007) and maternal depression (F(1,22) ¼ 4.54, P ¼ 0.04), suggesting that the difference in spelling scores was smaller with older survivors and when maternal depression scores were low. For the difference in internalizing scores, which reflected more internalizing problems for siblings than for survivors, the significant model (R2 ¼ 0.51, F(6,26) ¼ 4.59, P ¼ 0.0026) included history of cranial radiation (F(6,26) ¼ 3.35, P ¼ 0.05) and diagnosis (F(4,26) ¼ 3.04, P ¼ 0.03). This analysis suggests that the difference was smaller if the survivors had combined CRT and TBR or a diagnosis of neuroblastoma or Hodgkin’s lymphoma. Finally, none of the variables tested (personal, clinical and familial) were associated with the difference between survivors and siblings in physical QOL, suggesting that this difference is primarily a result of disease and HSCT treatment.

Discussion Contrary to predictions, survivors of HSCT performed as well in global and specific cognitive outcomes as their siblings but better than their siblings in PO. As predicted, they showed some deficits in educational outcomes and physical QOL. Moreover, their psychosocial QOL was rated as good as that of their siblings and, as a group, they presented with less internalizing problems than their siblings. These encouraging results support the previous longitudinal outcomes in this population, which showed improvement on PIQ and stable overall cognitive performance during the first 2 years post-HSCT, outcomes that were equivalent to or better than the normative values.3 It was surprising, however, that survivors were in fact doing better than their siblings on the specific index of PO, which measures specific ability to think in terms of visual images

and manipulate them with fluency. This ability is associated with persistence and alertness,30 and perhaps reflects the survivors’ experiences during the hospitalization and recovery period. During this period, survivors usually spend a substantial amount of time playing video games, which may enhance the skills measured by the PO index. It was not a surprising finding that two familial factors, maternal age and family cohesion, were associated with the difference in scores in favor of the survivors in PO. This result suggests that the children experienced different environments, one that may have resulted in greater individual attention in favor of the survivors because of their medical condition. This finding, however, is limited by the small sample size. Another familial factor, maternal depression scores, was associated with the difference in spelling. Thus, if mothers had high depression scores, survivors had lower spelling scores than their siblings, suggesting that survivors’ attention and memory for writing might have been influenced by changes in maternal mood. It was not surprising, however, to see that the difference in spelling was smaller for older groups, as older children are more likely to have learned spelling patterns before HSCT. Thus, the findings of this study along with the previous longitudinal educational outcomes3 suggest that a younger age at HSCT and indices of poor maternal psychological well being (measured by depression scores) may be risk factors for their educational outcomes. Consequently, these findings highlight the importance of early school attendance for learning the fine details of written language before HSCT, and identifying an area of intervention focus for schooling children during the first 2 years post-HSCT. Moreover, these findings also suggest that family support and counseling pre- and post-HSCT may result in indirect positive effects on cognitive and educational outcomes. Although, compared with their siblings, survivors, as a group, did not present with internalizing difficulties, it was interesting to see that survivors with a history of cranial radiation or a diagnosis of neuroblastoma or Hodgkin’s lymphoma were likely to have as high internalizing scores as their siblings. This finding raises the possibility that survivors with a history of cranial radiation, and those who survive neuroblastoma and Hodgkin’s lymphoma, are potentially at risk for internalizing problems. It is important to stress that neither survivors nor siblings, as a group, had mean internalizing scores in the clinical range. This attests to children’s resilience to the effects of traumatic medical experiences. Still, the fact that siblings in general tended to have more internalizing problems (anxiety, depression and social withdrawal) than survivors supports some earlier11 and recent reports on post-traumatic stress symptoms in siblings of children with cancer,10 and suggests that some siblings, in fact, were reported to have internalizing scores in the clinical range. It was not surprising to find poorer physical QOL in survivors compared with siblings, given their previous disease and aggressive treatment. It was interesting to see, however, that in spite of these physical limitations, psychosocially they were rated to be doing at least as well as their siblings. Finally, none of the additional personal Bone Marrow Transplantation


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and familial factors examined in this study were associated with the group difference in physical QOL, which suggests that this difference was directly a result of the disease and treatment, particularly, undergoing HSCT. In spite of the physical problems, however, survivors remain cognitively and emotionally resilient and continue to live, what appear to be, well-adjusted lives. The fact that our results show lesser deficits than reported previously may also reflect current less-aggressive protocol treatments, for example, reduced cranial radiation for ALL patients. This study has several limitations. A small sample and missing data resulted in reduced statistical power and limited the contribution of this study. Having a small sample size is not unusual in research with this medically vulnerable population faced with poor health, many stressors and high mortality rates.4 Comparing the outcomes of these survivors with those of their siblings is an asset as it controls for both environmental and genetic variance. Conversely, having the mother complete reports on both survivors and siblings limits the data on questionnaires to maternal perspective. The study was also limited by the availability of siblings as not all the survivors have a sibling close in age to complete the assessment measures. Although there are suggestions that being a sibling donor may make a difference in the sibling outcomes, comparisons of sibling donors and non-donors could not be made due to the small sample size of donors (five). Future studies should compare these outcomes among these groups of siblings and survivors. Despite these limitations, the outcomes of this comprehensive comparative study are unique, as they illustrate the resilience of survivors and the impact of pediatric HSCT within the family. In conclusion, 2 years post-HSTC survivors’ PO and psychological adjustment seem to be at least as good as those of their siblings, but their physical QOL and educational outcomes showed some deficits. Child characteristics, such as age, but mainly familial factors (maternal age and depression and family cohesion) seem to be associated with the difference in cognitive and educational outcomes between survivors of HSCT and their siblings. Conversely, clinical factors—history of cranial radiation and type of diagnosis—seem to be associated with psychological adjustment differences. These findings provide new knowledge for corroboration by future researchers. Finally, these findings have important implications for comprehensive family care, particularly in light of the important positive association of the outcomes with maternal well being and age.

Acknowledgements This research was supported by grants from the Hospital for Sick Children Foundation, New Initiatives; Elizabeth Lue Bone Marrow Foundation and the National Cancer Institute of Canada. The authors declare that no financial interests or relationships exist. We thank K Sumbler and T Smith for their help in collecting data for this research and G Andrews, V Jovcevska, T Teall and K Hancock for their help in preparing the manuscript. Bone Marrow Transplantation

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