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Long-Term Recipient Health-Related Quality of Life and Donor-Recipient Relationship following Sibling Pediatric Hematopoietic Stem Cell Transplantation
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Biology of Blood and Marrow Transplantation journal homepage: www.bbmt.org
Long-Term Recipient Health-Related Quality of Life and DonorRecipient Relationship following Sibling Pediatric Hematopoietic Stem Cell Transplantation ska, Jacek Wachowiak Olga Zajac-Spycha»a*, ˛ Anna Pieczonka, Ma»gorzata Baran Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Poznan, Poland
Article history: Received 16 August 2019 Accepted 8 October 2019 Keywords: Quality of life Siblings Donor Children Hematopoietic stem cell transplantation
A B S T R A C T Despite the fact that the choice of donors and the number of sources of hematopoietic stem cells have increased, a sibling remains a preferred donor for allogeneic hematopoietic stem cell transplantation (HSCT). Transplant donation between siblings is a unique life experience that may have an impact on their future relationship. The aim of the study was to quantitatively measure the quality of life (QoL) in patients who underwent transplant and to describe the relationship between a recipient and a sibling donor after HSCT. We identified and invited 82 adults aged 18.0 to 38.7 years (median, 23.6) who underwent HSCT in our center and their sibling donors to participate in this survey. Forty-five patients (54.9%) and their siblings consented to take part in the study. The studied group consisted of 45 matched siblings donor (MSD)-HSCT recipients (19 women and 26 men) aged 18.0 to 36.2 (median, 28.5) years, who underwent MSD-HSCT at the age of 5.8 to 16.3 (median, 11.9) years, and their sibling donors aged 21.0 to 36.0 (median, 31.0) years, who were aged 11.2 to 20.2 (median, 15.5) years at bone marrow harvesting. For QoL and sibling relationship assessment, we used the Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACT-BMT) and the Adult Sibling Relationship Questionnaire (ASQR). Higher scores indicate better quality of life in each scale of the FACT-BMT and the more significant is the factor in a sibling relationship measured by the ASQR. The questionnaires were given to both subgroups, HSCT recipients and donors, and the results were compared with each other. The overall result of the FACT-BMT questionnaire was 117 § 35.0. The highest QoL was found in the functional (25.0 § 3.5) and social well-being (25.0 § 3.5) subscales, whereas the worst was in the emotional well-being (18.0 § 9.5) subscale. Statistically, the QoL score was not influenced by current age (P = .378), age at the moment of HSCT (P = .256), and sex (P = .117). Being a recipient or a donor of HSCT was not a significant factor associated with warmth (2.6 § 0.5 versus 3.1 § 0.5; P = .830) and conflict (2.0 § 0.7 versus 2.1 § 1.2; P = .886) within the sibling relationship, whereas recipients scored significantly lower in rivalry within the sibling relationship compared with HSCT donors (0.8 § 0.3 versus 1.2 § 0.2; P = .012). The FACT Treatment Outcome Index remained the only significant predictor of warmth in the sibling relationship between HSCT recipient and donor. QoL in adult patients after HSCT in childhood was good. Sibling donor-recipient relationship is unbalanced, with a higher level of rivalry presented among donors. Further multicenter studies based on a larger cohort of patients are necessary to assess all aspects of the sibling relationship after transplantation experience. © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
INTRODUCTION Allogeneic hematopoietic stem cell transplantation (HSCT) is commonly used as a treatment for patients with a variety of diseases, mainly hematologic malignancies. Even though it offers a potential cure, especially when other treatments have failed, there is still a significant risk of severe complications and side effects, including mortality [1-3]. Nevertheless,
Financial disclosure: See Acknowledgments on page 6. *Correspondence and reprint requests: Olga Zajac-Spycha»a, ˛ PhD, Department of Pediatric Oncology, Hematology and Transplantology University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznan, Poland. E-mail address: [email protected] (O. Zajac-Spycha»a). ˛
allogeneic HSCT remains a potentially life-saving treatment, and the number of these procedures is increasing and indications for its clinical application have broadened [4]. Although there are more unrelated donor HSCTs, the number of HLA-matched sibling donors in the pediatric population still represents 30% to 40% of all allogeneic transplants [1-7]. The search for a donor usually begins among the patient’s siblings, where there is a 25% chance that each sibling will be HLA matched. Stem cell collection is performed usually by means of bone marrow harvest. The most frequent symptoms experienced by donors after donation are mild and transient, whereas the risk of severe adverse events is small [1]. Although physical aspects and the safety of stem cell collection
https://doi.org/10.1016/j.bbmt.2019.10.009 1083-8791/© 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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in pediatric siblings have been studied extensively, little is known about long-term psychological and emotional effects of the transplant on donors and their relationship with recipients. Transplant donation is a unique life experience that may have an impact on their future relationship. For a large proportion of HSCT survivors, curing the underlying disease may not be accompanied by full recovery. Instead, they may have significant physical and psychological morbidities, potentially threatening HSCT recipients’ healthrelated quality of life (HRQoL), which is directly affected by changes in health [8]. HRQoL can be defined as the functional effect of illness and its consequent therapy on an individual as perceived by the patient [9]. A growing literature documents that transplant procedures may severely compromise the quality of life (QoL) of patients [10]. HRQoL has tremendous importance for pediatric HSCT patients as it is performed to cure otherwise incurable diseases, and if successful, the life expectancy of recipients is comparable with the general pediatric population. One of the essential components of patients’ QoL is their close relations with family members, especially siblings. Sibling relationships are universal and can drive development in powerful ways. Sibling relationships are embedded in and connected to other social relationships within the family and among peers. During some life stages, people spend more time with their siblings than with their parents or peers. Moreover, the quality of sibling relationships may positively affect adolescent identity, self-esteem, and peer relationships, particularly during stressful life periods. Also, the impacts of the sibling relationship may endure in later life: research has associated healthy sibling relationships in childhood with improved adult mental health [11]. Patients and their sibling donors need to face significant psychological distress that may have an impact on their relationship in the future. There are only a few studies exploring sibling HSCT donors’ experiences, and those that have been performed focus on the per-donation period that is affected by the experience of lifethreatening illness of sick siblings [12]. Thus, the present study sought to provide the long-term QoL in pediatric sibling HSCT recipients, especially HRQoL. In addition, the recipient-donor relationship was described with a special focus on the correlation between QoL and sibling relationship. The hypothesis of the study was that it is possible that sibling relationship years after transplantation may be still affected by this experience and may be the one of the reasons for the decline in QoL of HSCT recipients. PATIENTS AND METHODS Participants and Procedure Between 1989 and 2014, 215 children underwent allogeneic HSCT from a sibling donor at the Department of Pediatric Oncology, Hematology, and Transplantology at Poznan University of Medical Sciences. In total, 133 patients were not eligible for the follow-up study (68 [31.6%] patients died; 65 [30.2%] were under 18 years old at the time of study). Of the remaining 82 HSCT patients, 45 (54.9%) recipients and donors agreed to participate in the study. Finally, the studied group consisted of 45 recipients (19 women, 26 men) aged 18.0 to 36.2 (median, 28.5) years at the time of the study who were 5.8 to 16.3 (median, 11.9) years at the moment of HSCT and 45 donors (23 women, 22 men) aged 21.0 to 36.0 (median, 31.0) years at the time of the study who were 11.2 to 20.2 (median, 15.5) years at the moment of donation. A flow diagram of patient selection is shown in Figure 1. The conduct of this cross-sectional study was approved by the local institutional review board. A package including information about the study, a consent form, and the battery of questionnaires was sent to the childhood HSCT recipients and donors. The written consent form was signed by all participants. Completed questionnaires were returned via reply-paid envelopes. Assessment Measures At consent, recipients and donors completed paper questionnaires. All participants completed the same demographic survey, including age, sex,
marital status, perceived economic status (individuals were asked to self-rate their economic status), level of education, and inhabitancy; a relationship assessment measure; and the QoL scales. The Functional Assessment of Chronic Illness Therapy Bone Marrow Transplant (FACT-BMT) consists of the FACT-G (Functional Assessment of Cancer Therapy General) developed to assess QoL of patients with cancer in the areas of physical, social/family, emotional, and functional well-being, as well as a bone marrow transplant (BMT) subscale specific to bone marrow transplant. With patients’ answers applying to the past 7 days, the FACT-G has 27 items and the BMT subscale has 12 items. The FACT-G is scored by summing the 5 subscales, whereas the FACT-BMT includes 12 other items constructed to be compatible with the FACT-G. Scoring procedures for the FACT-G and FACT-BMT are similar and consist of summing the items with reversed scoring for several items, which produces individual subscale scores and an overall score. Moreover, the FACT Treatment Outcome Index (FACTTOI) was also assessed to form a precise and optimally sensitive measure of treatment effects. The FACT-TOI combines the physical well-being subscale, the functional well-being subscale, and the 12 items of the FACT-BMT [13]. Higher scores indicate better quality of life in each scale. Moreover, results above 75% of the maximum score in each scale are considered reference values for the healthy population. Both scales have been used extensively in cancer populations and in comparisons with other measures of QoL; the FACTBMT is one of the more comprehensive instruments of QoL available [4]. The Adult Sibling Relationship Questionnaire (ASRQ) by C. Stocker, R. Lanthier, and W. Furman is a tool designed to measure relationships between siblings in the period of adulthood. The ASRQ measures participants’ perceptions of their sibling’s behavior and feelings toward them, as well as their own behavior and feelings toward their brother or sister who was an HSCT recipient or donor. The assessed areas include the perception of the HSCT recipients, their behaviors and feelings toward their donors, and the donors’ perception of the behaviors and feelings toward the recipients [14]. The questionnaire consists of 49 items, which form 8 scales that are combined to form three higher-order factors: warmth (intimacy, knowledge, emotional support), conflict (dominance, antagonism, quarreling), and rivalry (maternal rivalry and paternal rivalry). All the ASRQ items (except rivalry) are assessed on a Likert scale ranging from hardly anything (1 point) to extremely much (5 points). The items showing the level of rivalry between siblings are assessed on the scale from 0 (the child is not favored by their parents) to 2 points (the parents usually favor one child in relation to the other child) [15]. The higher the score is, the more significant is the factor in a sibling relationship. This scale measures only the direct donor-recipient relationship, but not generally being favored within family. Statistical Analysis Qualitative and quantitative data were collected and evaluated using Statistica package version 10 (StatSoft Poland, Warsaw, Poland). Outcomes included recipient and donor scores on the ASRQ and recipient FACT-BMT. All outcomes were not normally distributed. The Fisher exact test or the Mann-Whitney U test was used to compare noncategorical data. All tests were 2-sided, and a P value <.05 was considered to indicate a statistically significant difference; there was no adjustment for multiple testing. Pearson correlation coefficients were calculated to examine associations between the QoL dimensions and the recipient-donor relationship.
RESULTS Responders versus Nonresponders Forty-five recipients-donor pairs participated in the study, constituting 20.9% of the entire patient population after HSCT (215 patients) and 54.9% of all HSCT patients who were eligible for the study (82 patients). Thirty-eight percent of the entire HSCT recipient population was approached, but 37 (17.2%) refused participation. The nonresponders in the study were compared with the respondents using the following variables: current age, age at HSCT, time since HSCT, sex, and diagnosis. The nonresponders and responders did not differ regarding current age (P = .757), age at HSCT (P = .324), sex (P = .911), and diagnosis (P = .278). However, the group of nonresponders had a longer median follow-up time since HSCT (respondents = 89.2 months, nonresponders = 199.1 months; P < .001). The sociodemographic and disease-specific data of the studied group are summarized in Table 1. Quality of Life The median, interquartile range, and ranges of scores for the FACT-G subscales, BMT subscale, total score, and FACT-TOI
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Assessed for eligibility (n=215)
Excluded for medical reasons (n=133) Died (n=68) age <18 years (n=65)
Invited by leer (n=82)
Did not parcipate (n=37) Untraceable (n=6) Declined (n=31)
Parcipated (n=45)
recipients (n=45; 19 women, 26 men) age:18.0 – 36.2 (median: 28.5) years
donors (n=45; 23 women, 22 men) age: 21.0 – 36.0 (median: 31.0) years
Figure 1. Flow diagram of HSCT recipient selection.
are presented in Table 2. The median FACT-BMT score was 117.0 § 35.0, with domain-specific values of 24.0 § 9.5 for the physical well-being subscale, 25.0 § 3.5 for the functional well-being subscale, 18.0 § 9.5 for the emotional well-being subscale, 25.0 § 3.5 for the social well-being, and 31.0 § 5.0 for HSCT-specific complaints. General QoL measured by FACTG was 86.0 §21.5, whereas FACT-TOI measuring HSCT effect on QoL was 81.0 § 14.5. There was no significant association between the QoL measured by FACT scores and the sociodemographic variables, including current age (P = .378), age at the moment of HSCT (P = .256), and sex (P = .117). Recipient-Donor Relationship Descriptive statistics and comparison for each of the ASRQ scales from the recipient and donor perspectives are provided in Table 3. Being a recipient or a donor of HSCT was not found to be a significant factor associated with warmth within the sibling relationship (2.6 § 0.5 versus 3.1 § 0.5; P = .830). Similarly, there was no significant difference of conflict within the sibling relationship after transplantation (2.0 § 0.7 versus 2.1 § 1.2; P = .886). In contrast, being the HSCT recipient was found to be a significant factor associated with lower rivalry within the sibling relationship when compared with HSCT donors (0.8 § 0.3 versus 1.2 § 0.2; P = .012). Significantly lower rivalry among HSCT recipients was confirmed for both
maternal and paternal rivalry scales (0.7 § 0.3 versus 1.2 § 0.4; P = .029 and 0.8 § 0.2 versus 1.1 § 0.2; P = .028, respectively). All results remained unchanged after controlling for the influence of sex of the sibling (same-sex and opposite-sex sibling), current age difference, and time from HSCT. Impact of Sibling Relationship on QoL of HSCT Recipients Linear model regression analysis was conducted to determine which of the FACT subscales best predicted the sibling relationship (Table 4). Regression analysis revealed that only the FACT-TOI measuring the transplant effect on QoL remained a significant predictor of warmth in the sibling relationship between HSCT recipient and donor. There were no significant changes in regression when demographic factors were considered as predictors. DISCUSSION The study aimed at understanding the long-term HRQoL of pediatric patients who received a transplant from their healthy sibling and an adult recipient-donor relationship after such a unique life experience. A possible correlation between recipients’ QoL and the sibling relationship was also identified. Some findings of this study were partially concordant with the precedent studies on this topic. Some others seemed to take other directions.
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Table 1 Sociodemographic Characteristics of the Participants HSCT Recipients (n = 45)
HSCT Donors (n = 45)
Characteristic
Frequency
%
Frequency
%
Sex: male
26
57.8
22
48.9
HM
37
82.2
—
—
BMFS
8
17.8
Married
27
60.0
37
82.2
Single
14
31.1
7
15.6
Not reported
4
8.9
1
2.2
Higher education
29
64.4
39
86.7
Secondary education
13
28.9
6
13.3
Primary school
3
6.7
0
0
Low
21
46.7
14
31.1
Medium
22
48.9
30
66.7
High
2
4.4
1
2.2
>500,000
2
4.4
4
8.9
201,000-500,000
22
48.9
18
40.0
21,000-200,000
14
31.1
18
40.0
Up to 20,000
7
15.6
5
11.1 Range
Diagnosis
Current marital status
Education
Perceived economic situation
Inhabitancy
Median
Range
Median
Age at diagnosis, yr
11.9
5.8-16.3
15.5
11.2-20.2
Current age, yr
28.5
18.0-36.2
31.0
21.0-36.0
Time from HSCT, mo
90.1
13.9-222.4
—
—
HM indicates hematologic malignancy; BMFS, bone marrow failure syndrome; — n/a.
First, the overall finding was that the pediatric patients who underwent transplantation reported a good level of QoL years after transplant, with low HSCT-specific complaints and a very good perception of self-functioning. General QoL and measurement of the HSCT effect on QoL in the studied group were good and comparable to healthy population norms (i.e., >75% of maximum score and also in line with other reports) [2,16]. Previous studies have also found that HSCT recipients experience acceptable physical health and exhibit good psychological and social behavior with no difference in terms of self-esteem compared with normal matched controls [17,18]. The most important observation of the study is that recipients and donors’ descriptions of their long-term psychological and emotional impact on the sibling relationship supported the hypothesis that the 2 groups experience both shared and unique consequences of family bone marrow donating. These
results clearly elucidate the complexity and persistence of the sibling relationship after bone marrow donation and indicate that this may result from the experience of sibling bone marrow donation [1,19]. To understand the higher level of rivalry presented by donors years after donation, we need to try to understand their situation at the time of transplant. Sibling donors have the dual role of being a family member and a donor, which may entail psychological vulnerability in that their role differs from that of the sibling recipients and other family members. This role is also different from that of an unrelated donor, who volunteered to the registry and does not know the recipient. In sibling donating, the donors, as other family members, are focused on the sick sibling while also worrying about themselves and feeling obliged to donate. de Oliveira-Cardoso et al. [20] suggested in their study that sibling donors at the time before donation hide their emotions as they
Table 2 FACT Subscale Scores for HSCT Recipients Characteristic
Median
IQR
Range of Scores
% of the Maximum Score
Physical well-being
24.0
9.5
0-28
85.7
Functional well-being
25.0
3.5
0-28
89.3
Emotional well-being
18.0
9.5
0-24
75.0
Social well-being
25.0
3.5
0-28
89.3 79.6
FACT-G total
86.0
21.5
0-108
FACT-BMT
31.0
5.0
0-40
77.5
FACT-TOI
81.0
14.5
0-96
84.4
FACT-G + FACT-BMT total
117.0
35.0
0-148
79.1
IQR indicates interquartile range.
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Table 3 Characteristic and Comparison of the Sibling Relationship from HSCT Recipient and Donor Perspectives ASRQ Scale
HSCT Recipient
HSCT Donor
P Value
Median
IQR
Median
IQR
2.6
0.5
3.1
0.5
.830
Intimacy
2.5
1.5
3.2
1.3
.517
Knowledge
2.7
0.8
2.7
0.7
.465
Emotional support
3.1
1.5
3.1
1.1
.774
2.0
0.7
2.1
1.2
.886
Dominance
1.8
0.9
1.3
1.1
.568
Antagonism
2.0
1.3
2.2
0.8
.999
Quarreling
2.0
1.3
2.0
1.2
.461
0.8
0.3
1.2
0.2
.012*
Maternal rivalry
0.7
0.3
1.2
0.4
.029*
Paternal rivalry
0.8
0.2
1.1
0.2
.028*
Warmth
Conflict
Rivalry
With the exception of maternal rivalry and paternal rivalry, scale scores range from 1 to 5; higher scores indicate more of a given dimension. Maternal rivalry and paternal rivalry scores range from 0 to 2; higher scores indicate greater rivalry. The bold values indicate the main factors of sibling relationship. * P < .05.
do not want to upset the sick sibling or parents with their thoughts and emotions while feeling alone and uncertain but also responsible for the transplant outcome in the process of donation. Furthermore, donors’ lack of involvement in the decision to serve as a donor may damage the child donor’s sense of trust and autonomy, resulting in trauma related to bone marrow donation [21]. Our study suggests that the traumatic experience of being a donor affects the sibling relationship even years after HSCT. The donors seem to feel uncertain and thus present a significantly higher level of rivalry for parents’ favor than recipients, which suggests that the psychological distress related to bone marrow donation observed in the peritransplant period exists permanently in their future lives and affects the adult relationship with the recipient. Parenting plays a significant role in contributing to rivalry. Although parents may strive to remain unbiased when it comes to their kids, favoritism is actually very common, especially in the situation of a life-threatening disease such as ones that need HSCT. The parental favoritism negatively affects the mental health of all children in the family by creating resentment in the less-favored children, stress from high parental expectations for the favored child, strained sibling relationships, and other negative consequences. Moreover, perceived maternal or paternal favoritism could have a long-lasting effect on sibling relationships. Recollections of this perceived favoritism in childhood may actually have a greater impact than current favoritism on sibling relationships. Despite existing evidence that some pediatric HSCT donors experience the donation as physically and psychologically
stressful and calls for investigations into pediatric donor HRQoL, limited research has focused on HRQoL in pediatric HSCT donors. Donor children have been reported to have poorer HRQoL than did before and shortly after donation and then returned to normative levels by 1 year postdonation, but it should be noted that approximately 20% of donors exhibited clinically important QoL deficits even a year after HSCT [22]. The lower donor HRQoL scores near the time of donation could suggest that something specific to the donation experience is affecting HRQoL or be a result of having a sibling who is critically ill and at a particularly important medical intervention point. Nevertheless, donor experiences around the time of and following donation are likely to set the stage for longer-term donor QoL and sibling relationships. Thus, sibling donors need special attention from the transplant and the psychosocial support teams. The parents should listen to their donor child’s worries to enable sharing their feelings and concerns with them. Moreover, psychosocial support of the donor and family should be part of the long-term follow-up post-transplant [5]. One strength of our study is that we measured QoL and the sibling relationship from the recipients’ and donors’ own perspective using validated tools. Another strength is that we enrolled patients with different underlying diseases and at a different age at the time of transplant, which improves the generalizability of our findings. However, interpreting the presented findings must be tempered by acknowledging their limitations. The main limitation is that it was a single-center study and the respondent sample was relatively small in comparison with the total number of HSCTs performed, and the
Table 4 Linear Model Regression Analysis of FACT Subscales as a Function of Warmth, Conflict, and Rivalry Factors of the Sibling Relationship Predictors
Warmth
Conflict
b
P
Physical well-being
0.348
.673
Functional well-being
0.161
b
Rivalry P
b
1.172
.248
0.163
.906
0.176
.906
P .746
0.275
.746
0.046
.952
Emotional well-being
0.206
.868
0.321
.815
Social well-being
0.192
.876
0.180
.895
0.469
.553
FACT-BMT
0.111
.929
0.258
.851
0.500
.531
FACT-TOI
2.247
.034
1.038
.369
0.289
.637
FACT-G + FACT-BMT total
0.077
.943
0.786
.527
0.171
.800
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advances in peritransplant care between 1989 and 2014 were not taken into account. Moreover, the design of the study was cross-sectional, which prevented exploring the causality of observed findings. In addition, the quality of care provided by carers and the family atmosphere before the transplant were not examined for logistical reasons. Furthermore, there is an inherent bias risk of bias in self-report questionnaires (e.g., it could be that individuals with worse transplant experiences were less likely to respond), as well as risk of selection and recall bias, which cannot be rectified objectively. Nevertheless, the detailed exploration of the long-term perspective of the sibling relationship after family bone marrow donating and its role in shaping QoL in the pediatric HSCT recipient population makes this feature of our study unique. Understanding the sibling recipient-donor relationship is a complex task given the multitude of individual, family, transplant, biologic, and system variables that mediate the impact of the HSCT experience. However, the results of the study suggest that bone marrow donation makes the relationship unbalanced, with a higher level of rivalry for parents’ favor among donors even after successful transplantation and good HRQoL among recipients. Further multicenter studies based on a larger cohort of patients are necessary to assess all aspects of the sibling relationship years after the transplantation experience and finally to provide effective psychological interventions for an often overlooked population of pediatric sibling donors. ACKNOWLEDGMENTS The authors thank the associate editor and anonymous reviewers for their efforts to improve the quality of this manuscript. Financial disclosure: This work was supported by grant from Poznan University of Medical Sciences (502-14-01104119-10398). Conflict of interest statement: There are no conflicts of interest to report. REFERENCES € I, Lenhoff S, Bengtsson M. Being a haematopoietic stem 1. Kisch A, Bolmsjo cell donor for a sick sibling: Adult donors' experiences prior to donation. Eur J Oncol Nurs.. 2015;19(5):529–535. 2. Tremolada M, Bonichini S, Taverna L, Basso G, Pillon M. Health-related quality of life in AYA cancer survivors who underwent HSCT compared with healthy peers. Eur J Cancer Care (Engl). 2018;27(6):e12878. 3. Ljungman P, Bregni M, Brune M, European Group for Blood and Marrow Transplantation. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant.. 2010;45(2):219–234. 4. Sannes TS, Simoneau TL, Mikulich-Gilbertson SK, et al. Distress and quality of life in patient and caregiver dyads facing stem cell transplant: identifying overlap and unique contributions. Support Care Cancer. 2019;27(6): 2329–2337.
5. Hutt D, Nehari M, Munitz-Shenkar D, Alkalay Y, Toren A, Bielorai B. Hematopoietic stem cell donation: psychological perspectives of pediatric sibling donors and their parents. Bone Marrow Transplant.. 2015;50 (10):1337–1342. 6. Passweg JR, Baldomero H, Peters C, European Society for Blood and Marrow Transplantation EBMT. Hematopoietic SCT in Europe: data and trends in 2012 with special consideration of pediatric transplantation. Bone Marrow Transplant.. 2014 Jun;49(6):744–750. 7. Wachowiak J, Chybicka A, Kowalczyk JR, et al. Development and current use of in hematopoietic stem cell transplantation in children and adolescents in Poland: report of the Polish pediatric study group for hematopoietic stem cell transplantation of the Polish Society for Pediatric Oncology and Hematology. Transfus Apher Sci.. 2018;57(3):316–322. 8. Kim R, Son KL, Lee KM, et al. Temporal trajectory of quality of life and its predictors in recipients of hematopoietic stem cell transplantation. Ann Hematol.. 2018;97(8):1407–1415. 9. The World Health Organization Quality of Life assessment (WHOQOL): position paper from the World Health Organization. Soc Sci Med.. 1995;41 (10):1403–1409. 10. Devins GM, Mah K, Messner HA, Xenocostas A, Gauvin L, Lipton JH. Quality of life trajectories during the first year following hematopoietic cell transplantation: an inception cohort study. Support Care Cancer. 2018;26 (7):2379–2386. 11. Kothari BH, McBeath B, Sorenson P, et al. An intervention to improve sibling relationship quality among youth in foster care: results of a randomized clinical trial. Child Abuse Negl.. 2017;63:19–29. 12. Switzer GE, Bruce J, Pastorek G, et al. Parent versus child donor perceptions of the bone marrow donation experience. Bone Marrow Transplant.. 2017;52(9):1338–1341. 13. McQuellon RP, Russell GB, Cella DF, et al. Quality of life measurement in bone marrow transplantation: development of the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. Bone Marrow Transplant.. 1997;19(4):357–368. 14. Lanthier R, Stocker C, Furman W. Adult sibling relationship questionnaire. In: Touliatos, Perlmutter, Holden, eds. Handbook of Family Measurement Techniques: Vol. 2. Abstracts. Thousand Oaks, CA: Sage; 2001:53–54. 15. Walecka-Matyja ˛ K. Psychometric properties of the Polish adaptation of the Adult Sibling Relationship Questionnaire (ASRQ). Arch Psychiatry Psychother. 2014;16(4):77–88. 16. Uderzo C, Corti P, Pappalettera M, et al. Life satisfaction in young adults 10 or more years after hematopoietic stem cell transplantation for childhood malignant and nonmalignant diseases does not show significant impairment compared with healthy controls: a case-matched study. Biol Blood Marrow Transplant.. 2012;18(11):1759–1764. 17. Eiser C, Hill JJ, Vance YH. Examining the psychological consequences of surviving childhood cancer: systematic review as a research method in pediatric psychology. J Pediatr Psychol.. 2000;25(6):449–460. 18. Stam H, Grootenhuis MA, Last BF. Social and emotional adjustment in young survivors of childhood cancer. Support Care Cancer. 2001;9(7):489– 513. 19. Labott S, Pfammatter A. The influence of the donor-recipient relationship on related donor reactions to stem cell donation. Bone Marrow Transplant.. 2014;49(6):831–835. 20. de Oliveira-Cardoso EA, dos Santos MA, Mastropietro AP, Voltarelli JC. Bone marrow donation from the perspective of sibling donors. Rev Lat Am Enfermagem. 2010;18(5):911–918. 21. Wiener LS, Steffen-Smith E, Fry T, Wayne AS. Hematopoietic stem cell donation in children: a review of the sibling donor experience. J Psychosoc Oncol.. 2007;25(1):45–66. 22. Switzer GE, Bruce J, Kiefer DM, et al. Health-related quality of life among pediatric hematopoietic stem cell donors. J Pediatr.. 2016;178: 164–170.
Biology of Blood and Marrow Transplantation journal homepage: www.bbmt.org
Long-Term Recipient Health-Related Quality of Life and DonorRecipient Relationship following Sibling Pediatric Hematopoietic Stem Cell Transplantation ska, Jacek Wachowiak Olga Zajac-Spycha»a*, ˛ Anna Pieczonka, Ma»gorzata Baran Department of Pediatric Oncology, Hematology and Transplantology, Poznan University of Medical Sciences, Poznan, Poland
Article history: Received 16 August 2019 Accepted 8 October 2019 Keywords: Quality of life Siblings Donor Children Hematopoietic stem cell transplantation
A B S T R A C T Despite the fact that the choice of donors and the number of sources of hematopoietic stem cells have increased, a sibling remains a preferred donor for allogeneic hematopoietic stem cell transplantation (HSCT). Transplant donation between siblings is a unique life experience that may have an impact on their future relationship. The aim of the study was to quantitatively measure the quality of life (QoL) in patients who underwent transplant and to describe the relationship between a recipient and a sibling donor after HSCT. We identified and invited 82 adults aged 18.0 to 38.7 years (median, 23.6) who underwent HSCT in our center and their sibling donors to participate in this survey. Forty-five patients (54.9%) and their siblings consented to take part in the study. The studied group consisted of 45 matched siblings donor (MSD)-HSCT recipients (19 women and 26 men) aged 18.0 to 36.2 (median, 28.5) years, who underwent MSD-HSCT at the age of 5.8 to 16.3 (median, 11.9) years, and their sibling donors aged 21.0 to 36.0 (median, 31.0) years, who were aged 11.2 to 20.2 (median, 15.5) years at bone marrow harvesting. For QoL and sibling relationship assessment, we used the Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACT-BMT) and the Adult Sibling Relationship Questionnaire (ASQR). Higher scores indicate better quality of life in each scale of the FACT-BMT and the more significant is the factor in a sibling relationship measured by the ASQR. The questionnaires were given to both subgroups, HSCT recipients and donors, and the results were compared with each other. The overall result of the FACT-BMT questionnaire was 117 § 35.0. The highest QoL was found in the functional (25.0 § 3.5) and social well-being (25.0 § 3.5) subscales, whereas the worst was in the emotional well-being (18.0 § 9.5) subscale. Statistically, the QoL score was not influenced by current age (P = .378), age at the moment of HSCT (P = .256), and sex (P = .117). Being a recipient or a donor of HSCT was not a significant factor associated with warmth (2.6 § 0.5 versus 3.1 § 0.5; P = .830) and conflict (2.0 § 0.7 versus 2.1 § 1.2; P = .886) within the sibling relationship, whereas recipients scored significantly lower in rivalry within the sibling relationship compared with HSCT donors (0.8 § 0.3 versus 1.2 § 0.2; P = .012). The FACT Treatment Outcome Index remained the only significant predictor of warmth in the sibling relationship between HSCT recipient and donor. QoL in adult patients after HSCT in childhood was good. Sibling donor-recipient relationship is unbalanced, with a higher level of rivalry presented among donors. Further multicenter studies based on a larger cohort of patients are necessary to assess all aspects of the sibling relationship after transplantation experience. © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
INTRODUCTION Allogeneic hematopoietic stem cell transplantation (HSCT) is commonly used as a treatment for patients with a variety of diseases, mainly hematologic malignancies. Even though it offers a potential cure, especially when other treatments have failed, there is still a significant risk of severe complications and side effects, including mortality [1-3]. Nevertheless,
Financial disclosure: See Acknowledgments on page 6. *Correspondence and reprint requests: Olga Zajac-Spycha»a, ˛ PhD, Department of Pediatric Oncology, Hematology and Transplantology University of Medical Sciences, Szpitalna Str. 27/33, 60-572 Poznan, Poland. E-mail address: [email protected] (O. Zajac-Spycha»a). ˛
allogeneic HSCT remains a potentially life-saving treatment, and the number of these procedures is increasing and indications for its clinical application have broadened [4]. Although there are more unrelated donor HSCTs, the number of HLA-matched sibling donors in the pediatric population still represents 30% to 40% of all allogeneic transplants [1-7]. The search for a donor usually begins among the patient’s siblings, where there is a 25% chance that each sibling will be HLA matched. Stem cell collection is performed usually by means of bone marrow harvest. The most frequent symptoms experienced by donors after donation are mild and transient, whereas the risk of severe adverse events is small [1]. Although physical aspects and the safety of stem cell collection
https://doi.org/10.1016/j.bbmt.2019.10.009 1083-8791/© 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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in pediatric siblings have been studied extensively, little is known about long-term psychological and emotional effects of the transplant on donors and their relationship with recipients. Transplant donation is a unique life experience that may have an impact on their future relationship. For a large proportion of HSCT survivors, curing the underlying disease may not be accompanied by full recovery. Instead, they may have significant physical and psychological morbidities, potentially threatening HSCT recipients’ healthrelated quality of life (HRQoL), which is directly affected by changes in health [8]. HRQoL can be defined as the functional effect of illness and its consequent therapy on an individual as perceived by the patient [9]. A growing literature documents that transplant procedures may severely compromise the quality of life (QoL) of patients [10]. HRQoL has tremendous importance for pediatric HSCT patients as it is performed to cure otherwise incurable diseases, and if successful, the life expectancy of recipients is comparable with the general pediatric population. One of the essential components of patients’ QoL is their close relations with family members, especially siblings. Sibling relationships are universal and can drive development in powerful ways. Sibling relationships are embedded in and connected to other social relationships within the family and among peers. During some life stages, people spend more time with their siblings than with their parents or peers. Moreover, the quality of sibling relationships may positively affect adolescent identity, self-esteem, and peer relationships, particularly during stressful life periods. Also, the impacts of the sibling relationship may endure in later life: research has associated healthy sibling relationships in childhood with improved adult mental health [11]. Patients and their sibling donors need to face significant psychological distress that may have an impact on their relationship in the future. There are only a few studies exploring sibling HSCT donors’ experiences, and those that have been performed focus on the per-donation period that is affected by the experience of lifethreatening illness of sick siblings [12]. Thus, the present study sought to provide the long-term QoL in pediatric sibling HSCT recipients, especially HRQoL. In addition, the recipient-donor relationship was described with a special focus on the correlation between QoL and sibling relationship. The hypothesis of the study was that it is possible that sibling relationship years after transplantation may be still affected by this experience and may be the one of the reasons for the decline in QoL of HSCT recipients. PATIENTS AND METHODS Participants and Procedure Between 1989 and 2014, 215 children underwent allogeneic HSCT from a sibling donor at the Department of Pediatric Oncology, Hematology, and Transplantology at Poznan University of Medical Sciences. In total, 133 patients were not eligible for the follow-up study (68 [31.6%] patients died; 65 [30.2%] were under 18 years old at the time of study). Of the remaining 82 HSCT patients, 45 (54.9%) recipients and donors agreed to participate in the study. Finally, the studied group consisted of 45 recipients (19 women, 26 men) aged 18.0 to 36.2 (median, 28.5) years at the time of the study who were 5.8 to 16.3 (median, 11.9) years at the moment of HSCT and 45 donors (23 women, 22 men) aged 21.0 to 36.0 (median, 31.0) years at the time of the study who were 11.2 to 20.2 (median, 15.5) years at the moment of donation. A flow diagram of patient selection is shown in Figure 1. The conduct of this cross-sectional study was approved by the local institutional review board. A package including information about the study, a consent form, and the battery of questionnaires was sent to the childhood HSCT recipients and donors. The written consent form was signed by all participants. Completed questionnaires were returned via reply-paid envelopes. Assessment Measures At consent, recipients and donors completed paper questionnaires. All participants completed the same demographic survey, including age, sex,
marital status, perceived economic status (individuals were asked to self-rate their economic status), level of education, and inhabitancy; a relationship assessment measure; and the QoL scales. The Functional Assessment of Chronic Illness Therapy Bone Marrow Transplant (FACT-BMT) consists of the FACT-G (Functional Assessment of Cancer Therapy General) developed to assess QoL of patients with cancer in the areas of physical, social/family, emotional, and functional well-being, as well as a bone marrow transplant (BMT) subscale specific to bone marrow transplant. With patients’ answers applying to the past 7 days, the FACT-G has 27 items and the BMT subscale has 12 items. The FACT-G is scored by summing the 5 subscales, whereas the FACT-BMT includes 12 other items constructed to be compatible with the FACT-G. Scoring procedures for the FACT-G and FACT-BMT are similar and consist of summing the items with reversed scoring for several items, which produces individual subscale scores and an overall score. Moreover, the FACT Treatment Outcome Index (FACTTOI) was also assessed to form a precise and optimally sensitive measure of treatment effects. The FACT-TOI combines the physical well-being subscale, the functional well-being subscale, and the 12 items of the FACT-BMT [13]. Higher scores indicate better quality of life in each scale. Moreover, results above 75% of the maximum score in each scale are considered reference values for the healthy population. Both scales have been used extensively in cancer populations and in comparisons with other measures of QoL; the FACTBMT is one of the more comprehensive instruments of QoL available [4]. The Adult Sibling Relationship Questionnaire (ASRQ) by C. Stocker, R. Lanthier, and W. Furman is a tool designed to measure relationships between siblings in the period of adulthood. The ASRQ measures participants’ perceptions of their sibling’s behavior and feelings toward them, as well as their own behavior and feelings toward their brother or sister who was an HSCT recipient or donor. The assessed areas include the perception of the HSCT recipients, their behaviors and feelings toward their donors, and the donors’ perception of the behaviors and feelings toward the recipients [14]. The questionnaire consists of 49 items, which form 8 scales that are combined to form three higher-order factors: warmth (intimacy, knowledge, emotional support), conflict (dominance, antagonism, quarreling), and rivalry (maternal rivalry and paternal rivalry). All the ASRQ items (except rivalry) are assessed on a Likert scale ranging from hardly anything (1 point) to extremely much (5 points). The items showing the level of rivalry between siblings are assessed on the scale from 0 (the child is not favored by their parents) to 2 points (the parents usually favor one child in relation to the other child) [15]. The higher the score is, the more significant is the factor in a sibling relationship. This scale measures only the direct donor-recipient relationship, but not generally being favored within family. Statistical Analysis Qualitative and quantitative data were collected and evaluated using Statistica package version 10 (StatSoft Poland, Warsaw, Poland). Outcomes included recipient and donor scores on the ASRQ and recipient FACT-BMT. All outcomes were not normally distributed. The Fisher exact test or the Mann-Whitney U test was used to compare noncategorical data. All tests were 2-sided, and a P value <.05 was considered to indicate a statistically significant difference; there was no adjustment for multiple testing. Pearson correlation coefficients were calculated to examine associations between the QoL dimensions and the recipient-donor relationship.
RESULTS Responders versus Nonresponders Forty-five recipients-donor pairs participated in the study, constituting 20.9% of the entire patient population after HSCT (215 patients) and 54.9% of all HSCT patients who were eligible for the study (82 patients). Thirty-eight percent of the entire HSCT recipient population was approached, but 37 (17.2%) refused participation. The nonresponders in the study were compared with the respondents using the following variables: current age, age at HSCT, time since HSCT, sex, and diagnosis. The nonresponders and responders did not differ regarding current age (P = .757), age at HSCT (P = .324), sex (P = .911), and diagnosis (P = .278). However, the group of nonresponders had a longer median follow-up time since HSCT (respondents = 89.2 months, nonresponders = 199.1 months; P < .001). The sociodemographic and disease-specific data of the studied group are summarized in Table 1. Quality of Life The median, interquartile range, and ranges of scores for the FACT-G subscales, BMT subscale, total score, and FACT-TOI
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Assessed for eligibility (n=215)
Excluded for medical reasons (n=133) Died (n=68) age <18 years (n=65)
Invited by leer (n=82)
Did not parcipate (n=37) Untraceable (n=6) Declined (n=31)
Parcipated (n=45)
recipients (n=45; 19 women, 26 men) age:18.0 – 36.2 (median: 28.5) years
donors (n=45; 23 women, 22 men) age: 21.0 – 36.0 (median: 31.0) years
Figure 1. Flow diagram of HSCT recipient selection.
are presented in Table 2. The median FACT-BMT score was 117.0 § 35.0, with domain-specific values of 24.0 § 9.5 for the physical well-being subscale, 25.0 § 3.5 for the functional well-being subscale, 18.0 § 9.5 for the emotional well-being subscale, 25.0 § 3.5 for the social well-being, and 31.0 § 5.0 for HSCT-specific complaints. General QoL measured by FACTG was 86.0 §21.5, whereas FACT-TOI measuring HSCT effect on QoL was 81.0 § 14.5. There was no significant association between the QoL measured by FACT scores and the sociodemographic variables, including current age (P = .378), age at the moment of HSCT (P = .256), and sex (P = .117). Recipient-Donor Relationship Descriptive statistics and comparison for each of the ASRQ scales from the recipient and donor perspectives are provided in Table 3. Being a recipient or a donor of HSCT was not found to be a significant factor associated with warmth within the sibling relationship (2.6 § 0.5 versus 3.1 § 0.5; P = .830). Similarly, there was no significant difference of conflict within the sibling relationship after transplantation (2.0 § 0.7 versus 2.1 § 1.2; P = .886). In contrast, being the HSCT recipient was found to be a significant factor associated with lower rivalry within the sibling relationship when compared with HSCT donors (0.8 § 0.3 versus 1.2 § 0.2; P = .012). Significantly lower rivalry among HSCT recipients was confirmed for both
maternal and paternal rivalry scales (0.7 § 0.3 versus 1.2 § 0.4; P = .029 and 0.8 § 0.2 versus 1.1 § 0.2; P = .028, respectively). All results remained unchanged after controlling for the influence of sex of the sibling (same-sex and opposite-sex sibling), current age difference, and time from HSCT. Impact of Sibling Relationship on QoL of HSCT Recipients Linear model regression analysis was conducted to determine which of the FACT subscales best predicted the sibling relationship (Table 4). Regression analysis revealed that only the FACT-TOI measuring the transplant effect on QoL remained a significant predictor of warmth in the sibling relationship between HSCT recipient and donor. There were no significant changes in regression when demographic factors were considered as predictors. DISCUSSION The study aimed at understanding the long-term HRQoL of pediatric patients who received a transplant from their healthy sibling and an adult recipient-donor relationship after such a unique life experience. A possible correlation between recipients’ QoL and the sibling relationship was also identified. Some findings of this study were partially concordant with the precedent studies on this topic. Some others seemed to take other directions.
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Table 1 Sociodemographic Characteristics of the Participants HSCT Recipients (n = 45)
HSCT Donors (n = 45)
Characteristic
Frequency
%
Frequency
%
Sex: male
26
57.8
22
48.9
HM
37
82.2
—
—
BMFS
8
17.8
Married
27
60.0
37
82.2
Single
14
31.1
7
15.6
Not reported
4
8.9
1
2.2
Higher education
29
64.4
39
86.7
Secondary education
13
28.9
6
13.3
Primary school
3
6.7
0
0
Low
21
46.7
14
31.1
Medium
22
48.9
30
66.7
High
2
4.4
1
2.2
>500,000
2
4.4
4
8.9
201,000-500,000
22
48.9
18
40.0
21,000-200,000
14
31.1
18
40.0
Up to 20,000
7
15.6
5
11.1 Range
Diagnosis
Current marital status
Education
Perceived economic situation
Inhabitancy
Median
Range
Median
Age at diagnosis, yr
11.9
5.8-16.3
15.5
11.2-20.2
Current age, yr
28.5
18.0-36.2
31.0
21.0-36.0
Time from HSCT, mo
90.1
13.9-222.4
—
—
HM indicates hematologic malignancy; BMFS, bone marrow failure syndrome; — n/a.
First, the overall finding was that the pediatric patients who underwent transplantation reported a good level of QoL years after transplant, with low HSCT-specific complaints and a very good perception of self-functioning. General QoL and measurement of the HSCT effect on QoL in the studied group were good and comparable to healthy population norms (i.e., >75% of maximum score and also in line with other reports) [2,16]. Previous studies have also found that HSCT recipients experience acceptable physical health and exhibit good psychological and social behavior with no difference in terms of self-esteem compared with normal matched controls [17,18]. The most important observation of the study is that recipients and donors’ descriptions of their long-term psychological and emotional impact on the sibling relationship supported the hypothesis that the 2 groups experience both shared and unique consequences of family bone marrow donating. These
results clearly elucidate the complexity and persistence of the sibling relationship after bone marrow donation and indicate that this may result from the experience of sibling bone marrow donation [1,19]. To understand the higher level of rivalry presented by donors years after donation, we need to try to understand their situation at the time of transplant. Sibling donors have the dual role of being a family member and a donor, which may entail psychological vulnerability in that their role differs from that of the sibling recipients and other family members. This role is also different from that of an unrelated donor, who volunteered to the registry and does not know the recipient. In sibling donating, the donors, as other family members, are focused on the sick sibling while also worrying about themselves and feeling obliged to donate. de Oliveira-Cardoso et al. [20] suggested in their study that sibling donors at the time before donation hide their emotions as they
Table 2 FACT Subscale Scores for HSCT Recipients Characteristic
Median
IQR
Range of Scores
% of the Maximum Score
Physical well-being
24.0
9.5
0-28
85.7
Functional well-being
25.0
3.5
0-28
89.3
Emotional well-being
18.0
9.5
0-24
75.0
Social well-being
25.0
3.5
0-28
89.3 79.6
FACT-G total
86.0
21.5
0-108
FACT-BMT
31.0
5.0
0-40
77.5
FACT-TOI
81.0
14.5
0-96
84.4
FACT-G + FACT-BMT total
117.0
35.0
0-148
79.1
IQR indicates interquartile range.
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Table 3 Characteristic and Comparison of the Sibling Relationship from HSCT Recipient and Donor Perspectives ASRQ Scale
HSCT Recipient
HSCT Donor
P Value
Median
IQR
Median
IQR
2.6
0.5
3.1
0.5
.830
Intimacy
2.5
1.5
3.2
1.3
.517
Knowledge
2.7
0.8
2.7
0.7
.465
Emotional support
3.1
1.5
3.1
1.1
.774
2.0
0.7
2.1
1.2
.886
Dominance
1.8
0.9
1.3
1.1
.568
Antagonism
2.0
1.3
2.2
0.8
.999
Quarreling
2.0
1.3
2.0
1.2
.461
0.8
0.3
1.2
0.2
.012*
Maternal rivalry
0.7
0.3
1.2
0.4
.029*
Paternal rivalry
0.8
0.2
1.1
0.2
.028*
Warmth
Conflict
Rivalry
With the exception of maternal rivalry and paternal rivalry, scale scores range from 1 to 5; higher scores indicate more of a given dimension. Maternal rivalry and paternal rivalry scores range from 0 to 2; higher scores indicate greater rivalry. The bold values indicate the main factors of sibling relationship. * P < .05.
do not want to upset the sick sibling or parents with their thoughts and emotions while feeling alone and uncertain but also responsible for the transplant outcome in the process of donation. Furthermore, donors’ lack of involvement in the decision to serve as a donor may damage the child donor’s sense of trust and autonomy, resulting in trauma related to bone marrow donation [21]. Our study suggests that the traumatic experience of being a donor affects the sibling relationship even years after HSCT. The donors seem to feel uncertain and thus present a significantly higher level of rivalry for parents’ favor than recipients, which suggests that the psychological distress related to bone marrow donation observed in the peritransplant period exists permanently in their future lives and affects the adult relationship with the recipient. Parenting plays a significant role in contributing to rivalry. Although parents may strive to remain unbiased when it comes to their kids, favoritism is actually very common, especially in the situation of a life-threatening disease such as ones that need HSCT. The parental favoritism negatively affects the mental health of all children in the family by creating resentment in the less-favored children, stress from high parental expectations for the favored child, strained sibling relationships, and other negative consequences. Moreover, perceived maternal or paternal favoritism could have a long-lasting effect on sibling relationships. Recollections of this perceived favoritism in childhood may actually have a greater impact than current favoritism on sibling relationships. Despite existing evidence that some pediatric HSCT donors experience the donation as physically and psychologically
stressful and calls for investigations into pediatric donor HRQoL, limited research has focused on HRQoL in pediatric HSCT donors. Donor children have been reported to have poorer HRQoL than did before and shortly after donation and then returned to normative levels by 1 year postdonation, but it should be noted that approximately 20% of donors exhibited clinically important QoL deficits even a year after HSCT [22]. The lower donor HRQoL scores near the time of donation could suggest that something specific to the donation experience is affecting HRQoL or be a result of having a sibling who is critically ill and at a particularly important medical intervention point. Nevertheless, donor experiences around the time of and following donation are likely to set the stage for longer-term donor QoL and sibling relationships. Thus, sibling donors need special attention from the transplant and the psychosocial support teams. The parents should listen to their donor child’s worries to enable sharing their feelings and concerns with them. Moreover, psychosocial support of the donor and family should be part of the long-term follow-up post-transplant [5]. One strength of our study is that we measured QoL and the sibling relationship from the recipients’ and donors’ own perspective using validated tools. Another strength is that we enrolled patients with different underlying diseases and at a different age at the time of transplant, which improves the generalizability of our findings. However, interpreting the presented findings must be tempered by acknowledging their limitations. The main limitation is that it was a single-center study and the respondent sample was relatively small in comparison with the total number of HSCTs performed, and the
Table 4 Linear Model Regression Analysis of FACT Subscales as a Function of Warmth, Conflict, and Rivalry Factors of the Sibling Relationship Predictors
Warmth
Conflict
b
P
Physical well-being
0.348
.673
Functional well-being
0.161
b
Rivalry P
b
1.172
.248
0.163
.906
0.176
.906
P .746
0.275
.746
0.046
.952
Emotional well-being
0.206
.868
0.321
.815
Social well-being
0.192
.876
0.180
.895
0.469
.553
FACT-BMT
0.111
.929
0.258
.851
0.500
.531
FACT-TOI
2.247
.034
1.038
.369
0.289
.637
FACT-G + FACT-BMT total
0.077
.943
0.786
.527
0.171
.800
ARTICLE IN PRESS 6
O. Zajac-Spycha ˛ »a et al. / Biol Blood Marrow Transplant 00 (2019) 1 6
advances in peritransplant care between 1989 and 2014 were not taken into account. Moreover, the design of the study was cross-sectional, which prevented exploring the causality of observed findings. In addition, the quality of care provided by carers and the family atmosphere before the transplant were not examined for logistical reasons. Furthermore, there is an inherent bias risk of bias in self-report questionnaires (e.g., it could be that individuals with worse transplant experiences were less likely to respond), as well as risk of selection and recall bias, which cannot be rectified objectively. Nevertheless, the detailed exploration of the long-term perspective of the sibling relationship after family bone marrow donating and its role in shaping QoL in the pediatric HSCT recipient population makes this feature of our study unique. Understanding the sibling recipient-donor relationship is a complex task given the multitude of individual, family, transplant, biologic, and system variables that mediate the impact of the HSCT experience. However, the results of the study suggest that bone marrow donation makes the relationship unbalanced, with a higher level of rivalry for parents’ favor among donors even after successful transplantation and good HRQoL among recipients. Further multicenter studies based on a larger cohort of patients are necessary to assess all aspects of the sibling relationship years after the transplantation experience and finally to provide effective psychological interventions for an often overlooked population of pediatric sibling donors. ACKNOWLEDGMENTS The authors thank the associate editor and anonymous reviewers for their efforts to improve the quality of this manuscript. Financial disclosure: This work was supported by grant from Poznan University of Medical Sciences (502-14-01104119-10398). Conflict of interest statement: There are no conflicts of interest to report. REFERENCES € I, Lenhoff S, Bengtsson M. Being a haematopoietic stem 1. Kisch A, Bolmsjo cell donor for a sick sibling: Adult donors' experiences prior to donation. Eur J Oncol Nurs.. 2015;19(5):529–535. 2. Tremolada M, Bonichini S, Taverna L, Basso G, Pillon M. Health-related quality of life in AYA cancer survivors who underwent HSCT compared with healthy peers. Eur J Cancer Care (Engl). 2018;27(6):e12878. 3. Ljungman P, Bregni M, Brune M, European Group for Blood and Marrow Transplantation. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe 2009. Bone Marrow Transplant.. 2010;45(2):219–234. 4. Sannes TS, Simoneau TL, Mikulich-Gilbertson SK, et al. Distress and quality of life in patient and caregiver dyads facing stem cell transplant: identifying overlap and unique contributions. Support Care Cancer. 2019;27(6): 2329–2337.
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