Hematopoietic cell transplantation (HCT) is considered first-line therapy for many life-threatening oncologic, hematologic, and immunologic disorders. For patients in need of HCT, the first step is to identify a suitable donor source. Testing is initiated with evaluation of recipient human leukocyte antigen typing (HLA-typing) and compared to potential donors (related/unrelated) to determine the compatibility of the donor and recipient. Potential stem cell sources include bone marrow (BM) collected by BM harvest, peripheral blood stem cells (PBSCs) collected by apheresis, and umbilical cord/placental blood.
HLA-matched siblings have historically been considered the optimal donors for medical, biological, economic, and logistical reasons. Each sibling has a 25% chance of being a perfect HLA match for the recipient. Sibling donors are typically readily available and offer the best chance for fewer transplant-related adverse effects (eg, chronic graft vs host disease [cGVHD]). Although pediatric donation of BM or PBSC is considered to be medically safe for the donor, potential risks for complications exist. These are related to anesthesia, fatigue, nausea, and vomiting, bone pain associated with the administration of granulocyte colony stimulating factor before the collection of stem cells, pain associated with a central venous catheter insertion or a BM harvest, and less frequently, required blood transfusions, and acquired infections.[3,4]
A wide range of emotions related to the sibling donor experience has been reported. These include increased family closeness, improved relationships with the ill sibling, and a sense of tremendous pride in helping to save a life. Yet, negative responses for sibling donors have also been reported, including anxiety, depression, withdrawal, behavioral problems, anger, and responsibility for the transplant outcome.[4–17] They have also been found to have poorer quality of life during and after donation compared to healthy controls. Sibling donors have reported anxiety about donation and felt that there is a need for donation procedures to be better explained to them. Findings from studies conducted with children undergoing medical procedures reveal that providing children with comprehensive procedural information reduces stress and also improves memory.[19,20] No prospective studies examining educational tools and transplant knowledge in pediatric stem cell donors are currently available.
With a goal of enhancing the education provided to sibling donors, we developed a pilot study to assess and compare sibling donor comprehension and knowledge of transplant procedures over the donation trajectory at various time points pre and post-transplant and utilized newly developed educational interventions. We report on the outcome of our intervention.
2 Materials and methods
This was a prospective pilot study that enrolled sibling donors between the ages of 10 to 25 years of age, who were fluent in English or Spanish (verbal and written language), and who had been determined to be medically cleared to be a sibling donor for an NIH HCT study. Primary objectives were to evaluate sibling donor comprehension and knowledge of transplant procedures and compare changes in knowledge from baseline at several time points, which included: before providing protocol consent to serve as a donor, post-consent informational session, and following educational interventions. Secondary objectives were to assess the effectiveness of an educational intervention (either board game [ShopTalk] or a workbook as a learning tool for conveying information on stem cell donation and transplantation to pediatric donors) and should be to identify prospectively donors who may require additional preparation before stem cell collection. The study was approved by the National Cancer Institute Institutional Review Board. Patient consent or parental permission with minor age assent was provided as age-appropriate. Patients were enrolled from 2007 to 2017.
At Time point 1 (baseline, T1), a quiz to determine knowledge of stem cell donation procedures and transplantation in general was administered to enrolled donors. This was done before any formal consent conference or discussion with the transplant team.
At time point 2 (T2), which was within 24 to 48 hours of meeting with the transplant team, when donation procedures were reviewed in detail and following the patient and/or guardian provision of consent to proceed, the knowledge quiz was re-administered. Participants were then provided an age-based intervention. Participants aged 10 to 15 years played a board game called ShopTalk with cards teaching about stem cell donation. Participants aged 16 to 25 years reviewed an educational workbook designed at the medical center for stem cell donors. Both the game and the review of the workbook took place with a study investigator during a 45- to 60-minute session.
At time point 3 (T3), knowledge was re-assessed within 24 to 48 hours following the interventions.
2.3 Donation and transplant knowledge quiz
The quiz questions were derived from information in the donor harvest and transplant protocol consent forms and were designed for the reading level of children 10 years and older. It included questions that directly applied to the procedures the donor would undergo and items that could impact how the donor felt about donation after transplant. Two versions of the quiz were developed, one for donors whose stem cells were collected by Peripheral Blood (apheresis) and the other for donors whose cells were collected by BM. Each quiz consisted of 19 items, with multiple choice and True/False options, that reflected content included in the informed consent. Principal investigators, protocol research nurses, and an educational specialist reviewed the quiz content and format before study initiation (Table 1).
ShopTalk is a therapeutic board game for children and adolescents to share their thoughts and feelings about their illness in an emotionally safe, fun, and creative way.[21,22] ShopTalk consists of a colorful board with 10 stores, each with a set of 15 question cards related to the theme of the individual store. Questions are written in English and Spanish. The questions in each store are primarily open-ended questions, leaving room for creative responses. Two sets of stem cell donation and transplantation knowledge cards were developed for the purposes of this study (one for PBSC and the other for BM donation) and reflect the questions within the quizzes (Fig. 1).
2.4.2 Educational Workbook
Being a Stem Cell Donor is an educational workbook created by members of a multidisciplinary health care team for this study. It provides facts on PBSC and BM stem cell donation. It is written at a 7th grade reading level and includes visual aids and activities to allow participants to actively engage with the material discussed. Examples include a word search, using words that are specific to stem cell donation. The Table of Contents for the workbook can be found in Table 2.
Both interventions reviewed: the donor matching process, filgrastim administration before donation, apheresis, BM aspiration, and stem cell transplantation and possible complications.
2.5 Analysis and Statistical Design
Each quiz was scored for the percentage of questions answered correctly to provide a composite score. Mean test scores for Time 1, 2, and 3 are provided in Figures 2 to 4. Given the limited number of subjects enrolled on this protocol, the analyses are descriptive and exploratory.
Nineteen participants were enrolled in the study. Of these, 17 participants were fully evaluable and completed 3 time points. The other 2 were lost to follow-up. The mean age was 17.1 years, with 7 participants between the age of 10 and 15 years (mean age of 12.1) and 10 between the age of 16 and 25 years (mean age of 20.6). Demographic and disease characteristics are included Table 3.
Participants had a mean score of 59.6% at the baseline knowledge test. Individual questions that addressed how stem cells help patients and why the participant was a donor to his/her sibling were most often correct (94.1% and 88.2%, respectively). The question about how stem cells are collected was incorrect for more than half of the participants (52.9%). Similarly, few knew where in the body stem cells can be found (17.7%). Several donors were concerned that their stem cells could turn into unhealthy cells. One donor, age 11, thought he would need to be in the freezer, along with his stem cells. These donors were tremendously relieved when the correct information was provided.
Two questions asked about transplant outcomes. Approximately 70% of participants correctly answered the question, “There is no guarantee that my stem cells will cure my brother or sister.” Only 35.3% of participants were able to correctly identify the possible problems that might occur for the recipient post-transplant.
Mean score of 59.6% at baseline increased to a mean score of 68.6% after the informational session with medical providers and increased again to 88.5% after the protocol specified educational intervention. Scores were marginally higher for the older age group at baseline (4 points) and more so after the educational session (8 points), although this advantage changed direction after the intervention, by which time the younger age group had a mean score of 90% versus 87.6% for the older group. Mean test scores for Time 1, 2, and 3 are presented in Figures 2 to 4.
For example, several donors were concerned that their stem cells could turn into unhealthy cells. One donor, age 11, thought he would need to be in the freezer, along with his stem cells. These donors were tremendously relieved when the correct information was provided.
Limited interactive educational material on stem cell donation is available for pediatric donors. Knowing that sibling donors are at risk for anxiety about stem cell procurement procedures and may have limited understanding of the process or transplant in general, this protocol was developed to assess the role of discussion and specific educational interventions on improving knowledge before stem cell collection. Our results demonstrated, as would be expected, a trend for increased knowledge from baseline to after meeting with the medical provider with continued increase after the educational intervention was provided.
Assessment of baseline knowledge revealed that in general siblings’ knowledge about why the donor was chosen to be a donor and how stem cells can help the stem cell recipient was very good at baseline. Questions that were frequently answered incorrectly included where stem cells come from, how stem cells are collected, and where their stem cells would be stored. The intervention provided an opportunity for misperceptions to be addressed.
Knowledge about potential complications for the donor's sibling (transplant recipient) and the lack of a guarantee of cure suggests more education is needed. This supports findings from an earlier study where sibling donors expressed the need for more information about transplant outcome and complications. Preparing sibling donors for possible post-transplant medical sequalae is a critical factor to consider when planning programs and clinical services for this patient population. Along with realistic post-transplant expectations, it is important to help reduce feelings of responsibility if the recipient sibling develops complications such as cGVHD, graft failure, disease relapse, or death.
There were several important limitations to this pilot study. The protocol specified that the baseline assessment be obtained before meeting with the medical team (information/consent session). One notable barrier to protocol enrollment was that many donors had already had the initial meeting with the medical team, precluding enrollment on study. Although this suggests that information was being provided to sibling donors at an early time point, it did limit our ability to assess what increase in knowledge followed these interventions. Second, the study was originally designed to re-assess knowledge 1 month after the stem cell donation. Based on logistical constraints, this latter time point was not captured as many donors went back to their primary care physicians and did not follow-up with the HCT team. Future studies would benefit from long-term follow-up for assessment of the impact of knowledge on anxiety and preparedness for the collection procedure.[23,24] Third, diverse confounding variables included large participant age range, PBSC, and BM collection, 2 different educational interventions and various recipient diagnoses. Additionally, our interventions were not intended for the very young donors wherein procedural anxiety may be high, and comprehension low. Finally, the quiz was not paired with a psychosocial assessment. This would be important to include in future intervention studies. Yet, despite these limitations and the confounding variables, knowledge scores consistently increased following an educational intervention suggesting the importance of having additional tools for donors.
In 2010, the Bioethics Committee of the American Academy of Pediatrics published recommendations regarding the conditions under which it is acceptable for a minor sibling donor to donate cells for hematopoietic stem cell transplantation. One of these recommendations is for the emotional and psychosocial risks to the donor to be minimized. Providing comprehensive procedural information to children is known to reduce distress and improve memory in children undergoing medical procedures.[19,20] Offering visual and/or interactive information to sibling donors may increase knowledge and perhaps comfort with the donation process. Additionally, inquiring about the donor's individual learning style (eg, visual, auditory) can help tailor how information is provided. The results of this pilot study suggest that age-appropriate educational interventions following the medical consent informational session can increase knowledge in pediatric and adolescent and young adult donors. Opportunities for repetition and clarification of information about donation post the consent informational session may increase comfort and prevent and reduce anxiety associated with the donation process and transplantation for all stem cell donors, potentially improving their quality of life. Further investigation into evidence-based interventions has the potential to advance specific support for this often overlooked and remarkably generous, brave, and invaluable population.
Conflicts of interest statement
The authors declare that they have no financial conflict of interest with regard to the content of this report.
The authors thank the patients and their families who participated in this study. They thank Drs. Mackall, Wayne and Fry for their scientific support of this work. The authors also thank Drs Jennifer Kanakry and Dennis Hickstein for referring their patients to this study. The authors acknowledge the research nurses from the National Heart, Lung and Blood Institute and the National Cancer Institute, as well as the educators and physicians who reviewed the content within the quizzes and helped with scheduling the study assessments.
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