synopsis - anzctr.org.au v… · web viewroyal brisbane and women’s hospital. department of...

Title: The psychosocial impact of allogeneic stem cell donation on adult sibling donors

Study sites: Royal Brisbane and Women’s HospitalWestmead Hospital

The University of QueenslandPrinciple Investigators: Nienke Zomerdijk

Prof Jane TurnerProf Geoff HillProf David Gottlieb

Co-investigators: Dr Jacobus UngererAnnette Barnes

Protocol Version: 1.3Version date: 5th December 2016

TABLE OF CONTENTS

Royal Brisbane and Women’s HospitalDepartment of Clinical Haematology and Bone Marrow Transplant

University of Queensland

SYNOPSIS...........................................................................................................................................21. OBJECTIVES...............................................................................................................................22. BACKGROUND............................................................................................................................23. HYPOTHESES.............................................................................................................................34. SIGNIFICANCE............................................................................................................................35. PARTICIPANT SELECTION........................................................................................................46. STUDY PLAN...............................................................................................................................4

6.1 Adult sibling stem cell transplant donors..........................................................................46.1.1 Measures..........................................................................................................................4

6.2 BMT Coordinators.................................................................................................................66.2.1 Measures..........................................................................................................................7

6.3 Analysis.................................................................................................................................76.3.1 Saliva samples.................................................................................................................76.3.2 Interviews..........................................................................................................................8

Table 1. Schedule of events..........................................................................................................87. Statistical consideration............................................................................................................88. Safety...........................................................................................................................................99. Data management.......................................................................................................................9References..........................................................................................................................................9

RBWH SCT donation psychosocial impact Protocol Page 1Version 1.3, 5th December 2016


University of Queensland

SYNOPSISThis is a prospective cohort study. The aim is to investigate the psychosocial impact of being an adult sibling stem cell donor. The role Bone Marrow Transplant (BMT) Coordinators play in stem cell donation and their involvement in the particular aspects and stages of the donation process will also be examined. Sibling donor participants are aged 18 to 70 years old and will be recruited from the Royal Brisbane and Women’s Hospital (RBWH) and Westmead Hospital after informed consent.

Sibling donors eligible for recruitment include adult sibling donors of allogeneic transplant recipients, including those who have been recruited to participate in the RBWH HREC approved study, titled ‘Observational study of IL-17-related cytokines in stem cell donation’. Sibling donors will complete three interviews and provide three samples of saliva as a measure of stress at the following time points: (T1) within 2 weeks before the stem cell mobilisation commences; (T2) within 24hrs of the donors’ stem cell collection and; (T3) within 2 weeks of the 30-day anniversary of the stem cell collection. BMT Coordinators will complete one interview towards the end of study.

In addition, up to six adult sibling lymphocyte infusion donors will provide three saliva samples at the same time points as sibling HSC donors. The purpose of including this participant group is to pilot the potential effect of granulocyte colony-stimulating factor (GCSF) on salivary alpha-amylase levels.

The saliva samples will be stored at the RBWH BMT Laboratory and analysed at the RBWH Department of Chemical Pathology. All study samples and study-related data will be de-identified by the use of a study code.

1. OBJECTIVES The aim of this study is to explore the psychosocial impact of donating stem cells on adult sibling donors. The specific objectives are:

a) To describe the physical and psychosocial reactions of adult sibling stem cells donors before, during and post-donation.

b) To identify the social, psychological, physical and pragmatic (e.g. adequacy of preparation) factors which determine post-donation satisfaction and those which cause distress before, during and post-donation.

c) To identify if and how the health system meets the psychosocial needs of adult sibling donors to help guide future guidelines and inform an intervention.

2. BACKGROUNDAllogeneic stem cell transplantation (SCT) is a preferred curative therapy in the majority of haematological cancers. More than 24,000 allogeneic SCT’s are performed annually worldwide of which approximately 30% use cells donated by a sibling donor and 70% from unrelated donors [1]. Sibling donors are the optimal stem cell donor candidate based on their rapid availability and the excellent long-term transplant outcomes associated with their use. Collection occurs either via bone marrow harvest under general anaesthesia, or now more commonly, peripheral blood stem cell (PBSC) collection, which accounts for approximately 75% of allogeneic SCT’s today [2].

For adult sibling donors, compared with the medical aspects of SCT, the psychosocial impact has received far less attention. Our recent review of the literature identified a wide range of psychosocial complications [3-6]. Sibling donors experienced anxiety about GCSF injections, both in terms of physical pain and fear of the long-term effects [3, 4]. Sibling donor psychosocial reactions were associated with the recipient’s state of health [3, 4]. Sibling donors became emotionally invested and felt responsible for their recipient’s outcomes and became grieved and disappointed if the transplantation was unsuccessful. Specifically, graft-versus-host-disease (GVHD) and recipient mortality produced negative feelings following donation. Indeed, graft-versus-host-disease (GVHD)



University of Queenslandremains to be the major complication of allogeneic SCT and acute GVHD is the primary cause of transplant mortality. Psychological gains have also been reported, including gains in self-esteem, self-worth, happiness and relationship quality with the recipient [5].

Our literature review identified that the impact of donation can be influenced by the perceived adequacy of preparation for donation and emotional support. Previous studies have reported sibling donors felt anxious and unprepared regarding the short- and long-term side effects of GCSF and some believed they were at increased risk of developing leukaemia [4, 7]. Some sibling donors were worried if the transplant would have the desired outcome. The brevity of appointments resulted in sibling donors feeling their concerns were perceived as unimportant by medical staff. In consequence, some sibling donors reported feeling neglected and used merely as a means of curing the patient [4, 7].

While World Marrow Donor Association Standards ensure consistency in the assessment and care of unrelated donors, no such criteria exist for sibling donors. The European Society for Blood and Bone Marrow Transplantation annual meeting in 2013 highlighted that further information on how to cater to the needs of sibling donors is warranted. Further, our literature review highlighted methodological and design issues and a need for further prospective research. This study aims to provide the evidence that is needed to guide future guidelines and inform an intervention.

3. HYPOTHESES1. Perceived donor preparedness for stem cell collection correlates with post-donation

psychosocial reactions.2. Donor ambivalence pre-donation correlates with post-donation psychosocial reactions. 3. Perceived relationship closeness with the recipient correlates with feelings of guilt and

responsibility throughout the process.4. Donors who give a poor evaluation of their sibling’s health report negative psychosocial

reactions throughout the process. 5. Donors with a good overall perceived health-related quality of life report positive

psychosocial reactions throughout the process. 6. Salivary α-amylase (sAA) levels correlate with psychosocial reactions throughout the

process.

Negative reactions may include: guilt and responsibility, stress following the procedure, physical pain and discomfort, concern for their own health and other psychosocial aspects of having donated stem cells. These reactions in turn are hypothesised to lead to less positive psychosocial reactions in the short- and long-term post-donation.

4. SIGNIFICANCEThis study will provide evidence regarding the social, psychological, physical and pragmatic factors which determine post-donation satisfaction and those which cause distress in adult siblings throughout the donation process. Assessment pre-donation will identify those donors who are more likely to develop psychosocial complications pursuant to donation and thus might merit additional clinical attention. This study, for the first time, will evaluate the psychosocial impact of stem cell donation on normal adult sibling donors using a novel biological marker of stress.

There is no literature available on the perceptions of BMT Coordinators regarding the psychosocial aspects of sibling stem cell donation. The study will help with obtaining an understanding of the formalised strategies in place and the culture of value assigned to the psychosocial adjustment of sibling donors.

5. PARTICIPANT SELECTION Study participants are adults (age 18 to 70) who are undergoing planned allogeneic stem cell



University of Queenslanddonation for a sibling recipient. Participants will be recruited from the RBWH and Westmead Hospital after informed consent. Participation in this study does not preclude participation in other research studies provided it does not contravene the requirements of the other study.

6. STUDY PLANThis is a prospective cohort study. Adult sibling stem cell donor participants will complete three interviews and provide three samples of saliva and BMT Coordinator participants will complete one interview.

Study participants include: Adult sibling stem cell transplant donors of planned allogeneic transplant recipients.Adult sibling lymphocyte donors of planned lymphocyte infusion recipients. BMT Coordinators within the RBWH and Westmead Hospital Haematology and Bone Marrow Transplant Units.

6.1 Adult sibling stem cell transplant donorsSiblings undergoing planned stem cell mobilisation and collection.

The eligibility criteria are as follows: a. Age 18 to 70 years oldb. Able to provide informed consent

The BMT Coordinator will mention the study briefly to the donor prior to passing on the donor’s name to the Principal Investigator. Recruitment will occur when the donor visits the RBWH or Westmead Hospital for transplant planning/work up. Sibling donors will be provided with information about the study and invited to participate by Nienke Zomerdijk. In cases when this is not possible, a Clinical Trial Nurse or Bone Marrow Transplant Registrar will obtain donor informed consent. Written consent will be obtained via a returned donor information and consent form.

The sibling donors will complete three interviews and provide three samples of saliva at the following time points: (T1) Within 2 weeks before the stem cell mobilisation commences; (T2) Within 24 hours (pre- or post-donation) of the donors’ stem cell collection and; (T3) Within 2 weeks of the 30-day anniversary of the stem cell collection.

Data will be collected through a series of semi-structured interviews that may be administered via face-to-face or telephone. Participants recruited from the RBWH may choose their preferred option for participation whereas participants recruited from the Westmead Hospital will complete all interviews by telephone. A combination of previously validated quantitative and qualitative measures based on previous research with kidney, bone marrow and stem cell donors were incorporated in the design of the interviews. A panel of cancer care clinicians and academics assessed the appropriateness of the quantitative and qualitative items.

6.1.1 MeasuresDemographics. Donors are asked for their age, gender, country of birth, marital status, relationship to the recipient, and education.

Relationship closeness. The Autonomy and Relatedness Inventory (ARI)[8] is a 30-item scale that measures relationship quality, on eight relationship dimensions (for example, listening, control, acceptance) that cover positive and negative aspects of relationships. Items are rated on a 5-point scale and yield subscale scores that are scored such that a higher score on the subscale indicates the more positive side of the dimension. Similarly, the total score indicates the extent to which the overall relationship is positive. Factor analysis yielded two main factors, corresponding to the positive and negative aspects of relationships, and internal consistency for the total score is 0.90



University of Queensland[8].

Frequency of donor-recipient contact prior to the request for donation. (a) daily, (b) weekly, (c) monthly or (d) yearly/less frequent contact [4].

Psychological distress. The Kessler Psychological Distress Scale (K10) is a 10-item instrument designed to measure anxiety and depression. Each item pertains to an emotional state rated on a 5-point scale. The higher the total score, the greater the level of psychological distress reported by the participant. Reliability tests were done on the K10 using the 2000 Collaborative Health and Wellbeing Survey. The ending Cohen’s kappa and weighted kappa scores ranged from 0.42 to 0.74 indicating K10 is a moderately reliable instrument to detect mental health conditions in the general population.

Health-related quality of life. The World Health Organisation Quality of Life (WHOQOL-BREF) is an abbreviated version of the WHOQOL-100. The instrument comprises 26 items, which measure four

broad domains: physical health, psychological health, social relationships, and environment. Internal consistency of the domains ranged from .66 to .84 [9].

Ambivalence about donation. Using a scale developed by Simmons et al. [10] for use with kidney donors, this 7-item scale has been used in research on unrelated bone marrow donors [11] and

related stem cell donors [5]. These items measure ambivalence about donation (for example, “How hard a decision was it for you to decide to donate?”; “I sometimes wish the transplant patient was getting stem cells from somewhere else instead of from me”). Several possible responses are provided for each item, and they are scored so that for each item, 0=no ambivalence and 1=ambivalence. The higher the total score, the greater the overall ambivalence reported by the donor. Cronbach’s alpha in the kidney and bone marrow samples was 0.78 [10, 11].

Donation experience. Developed by Butterworth et al. [12], the individual’s reactions to the donation itself are measured on an 8-item scale. For example, donors are asked how stressful and painful the donation was, if they felt prepared, and if they would donate again. An overall score is not derived, but individual items are reviewed to understand the donation experience.

Recipient health. Donors rate their opinion of the recipient’s health using a Karnofsky performance status scale [13]. This is a rating on a 10 (dying) to 100 (normal; no evidence of disease) scale.

Guilt and responsibility. Two items, each rated on a 3-point scale, were developed by Butterworth et al. [12] to assess the donor’s feelings of guilt and responsibility. For the present study, they are phrased to assess anticipated feelings of guilt and responsibility, (that is, Will you feel responsible (or guilty) if the stem cells you donated do not work?). Responses range from very responsible (or guilty), Somewhat responsible (or guilty) to Not at all Responsible (or guilty). Items are scored so that a higher score indicates more guilt or responsibility, and the individual items are examined separately in the analyses (see Table 1).

Better person. This 10-item scale, developed by Simmons et al. [10] was developed to measure self-esteem in kidney donors. Items are adjusted for use with stem cell donors. Donors are asked to what extent they feel like a ‘better person’ for having donated (for example, donating stem cells makes one feel like he/she is somehow a bigger and more worthwhile person; rated on a 4-point agree–disagree scale). Items are scored so that higher scores indicate higher self-esteem because of donation. In the initial study of kidney donors, Cronbach’s alpha = 0.72 [10].

Qualitative questions



University of QueenslandIn addition to the validated measures listed above, the research team designed the following qualitative questionnaires based on previous experience as a research assistant in formal conversation with donors and previous sibling stem cell and bone marrow donor research [4, 12]:

Questionnaire 11. Decision to donate/ Did you at all hesitate in deciding to donate? 2. What was your motivation to donate? I.e. why are you donating? 3. Did you at all feel pressured to donate? 4. What are your thoughts and feelings about being a donor? 5. How prepared do you feel for the donation experience? 6. What were some of the sources of information that you accessed prior to donation? Use a

checklist of available sources:o Haematologisto Internet, incl. videoso BMT coordinatoro Bookso Friends/familyo General practitioner

7. What was the most helpful source of information about donation? 8. How do you think the hospital can improve donor preparation?

Questionnaire 21. Sources of emotional support and use of emotional support services of the hospital? 2. Adequacy of emotional support from the hospital:

o Not at all adequateo Moderately adequateo Adequate o Very adequate

3. How do you think the hospital can improve donor emotional support?

Questionnaire 31. Looking back, what are your thoughts and feelings about being a donor after donation? 2. Has donating changed your relationship with your sibling recipient or other family members? 3. What was the most challenging aspect of donation?

Saliva samplesSibling donors will provide three saliva samples. Study samples collected will measure salivary alpha-amylase activity. Salivary alpha-amylase activity is associated with sympathetic-adrenal-medullary activity, which reflects psychological stress [14-16]. This information will be compared with the self-reported data from the interviews.

6.2 Adult sibling lymphocyte infusion donorsAdult sibling lymphocyte donors of planned lymphocyte infusions recipients are included in this study to consider any potential effect GCSF may have on salivary alpha-amylase levels. These patients are an appropriate control group since white cells are collected from these donors by apheresis in the absence of any GCSF.

The eligibility criteria are as follows: a. Age 18 to 70 years oldb. Able to provide informed consent

The BMT Coordinator will mention the study briefly to the donor prior to passing on the donor’s name to the Principal Investigator. Recruitment will occur when the donor visits the RBWH or Westmead Hospital for transplant planning/work up. Sibling lymphocyte donors will be provided with



University of Queenslandinformation about the study and invited to participate by Nienke Zomerdijk. In cases when this is not possible, a Clinical Trial Nurse or Bone Marrow Transplant Registrar will obtain donor informed consent. Written consent will be obtained via a returned donor information and consent form.

The sibling lymphocyte donors will provide three samples of saliva at the following time points: (T1) Within 2 weeks before the lymphocyte collection; (T2) Within 24 hours (pre- or post-donation) of the donors’ lymphocyte collection and; (T3) Within 2 weeks of the 30-day anniversary of the lymphocyte collection.

6.3 BMT CoordinatorsBMT Coordinators within the RBWH and Westmead Hospital Haematology and Bone Marrow Transplant Units. The Coordinators will complete one interview, to be completed towards the end of the study. Written consent will be obtained via a returned BMT Coordinator information and consent form. BMT Coordinators will be approached and consented by Nienke Zomerdijk.

6.3.1 MeasuresDemographics. BMT Coordinators are asked for their age, gender, country of birth, professional training and clinical experience.

Qualitative questionsThe following qualitative questions were designed by the research team to explore the nature of the role of BMT Coordinators, the aspects of psychosocial care that they provide and the systems and processes in place, including responsiveness to donor stress:

1. What professional education and training have you completed to equip you with the skills to communicate with the donor and family to explain the emotional and physical aspects of donation to support informed decision-making?

2. What, if any, do you consider to be your role in responding to the donor and their family in regard to psychosocial issues that may arise before or after the transplant?

3. If yes to the above, do you feel you have adequate access to supervision to equip you with the necessary knowledge and skills to sensitively support the donor and their family going through psychosocial distress?

4. What systems and processes are in place, including responsiveness to donor stress and ethical tensions that may arise?

5. What are the formalised strategies for adverse outcomes, including referral pathways?6. Challenging scenarios encountered?

6.4 Analysis6.4.1 Saliva samples

Saliva will be collected using Salivettes and examined as a function of stress. Sibling donors are instructed to place the cotton swab into their mouths for 1-2 minutes and chew slightly [17]. The saturated swab should then be returned to the suspended insert and the Salivette should be closed firmly with the stopper. The Salivettes will be pre-labeled with the participant’s study code and date of birth. Sibling donors will be instructed to enter the time of collection on this label.

When possible, the samples are obtained at the same time as other routine hospital consultations (applicable to the RBWH only). In all other cases, the sibling donor will collect the saliva sample as per the instructions given and mail the sample in a pre-paid envelope to the RBWH Haematology/BMT Clinical Trials department where the samples are stored for batch testing.

The analysis of saliva samples is performed in batch mode at the RBWH Department of Chemical Pathology. Analysis to be undertaken includes the analysis of alpha amylase by a liquid handling platform (the Beckman Coulter AU-480) or similar technology.



University of Queensland6.4.2 Interviews

Qualitative data will be analysed as one data set using the six-stage thematic approach proposed by Braun and Clarke [18]. This involves: familiarisation with responses, generation of initial codes, collation of codes into potential themes, reviewing themes in relation to coded extracts and the entire data set, defining and naming themes and reporting on outcomes. To ensure consistency of coding, Nienke Zomerdijk will perform the independently to one other assessor. The data will be crosschecked and any discrepancies will be negotiated in discussion between both authors.

Table 1. Schedule of eventsEvent Baseline (T1) Within 24hrs of

stem cell infusion (T2)

30 Days post stem cell infusion (T3)

BMT CoordinatorsInformed consent XDemographics XQualitative questions XSibling SCT DonorsInformed consent XDemographics XDonor-recipient contact X Xa

Relationship closeness (ARI) X Xa

Psychological distress (K10) X X XQuality of Life (WHOQOL-BREF) X XAmbivalence XDonation experience X XRecipient health (KPS) X X Xa

Guilt X X XResponsibility X X XBetter person X X XQuestionnaire1 XQuestionnaire 2 XQuestionnaire 3 XSaliva sample X X XSibling lymphocyte infusion donorsSaliva sample X X XaThese items will not be asked if the recipient has died.Abbreviations: ARI, Autonomy and Relatedness Inventory; WHOQOL-BREF, World Health Organisation Quality of Life assessment – short version; KPS, Karnofsky Performance Status scale.

7. Statistical considerationAnalysis of historical sibling stem cell donors at RBWH demonstrates that an estimated 25 sibling donors are recruited per year. Enrolment is expected to be completed within 23 months, providing a potential sample size of 47 donors. Up to 10 sibling donors will be recruited from the Westmead Hospital. A total of 3 Bone Marrow Transplant Coordinators will be recruited from the two sites. Up to 6 sibling lymphocyte infusion donors will be recruited from the two sites to pilot the effect of GCSF on saliva.

Based on previous prospective studies [4, 5] of sibling donors that utilised 3 or more time-points, we expect a participation rate of 50%. Therefore, we expect that 57 sibling SCT donors will be eligible to participate and assume that 28 sibling SCT donors will agree to participate.



University of Queensland8. Safety

If any participant becomes distressed whilst participating in the study, notification will be made to Professor Jane Turner, an experienced consultation-liaison psychiatrist. Professor Turner will arrange for assessment and referral for specialised treatment appropriate to donors’ level of distress and geographic location.

9. Data managementAll study samples and study-related data will be de-identified by the use of a study code. De-identified data will be kept in a locked facility at the RBWH BMT Laboratory, the RBWH Department of Chemical Pathology and in the RBWH Haematology/BMT Clinical Trials office at RBWH and/or UQ School of Medicine, Mental Health Centre. These facilities are accessible only by a secure pass key by study staff. Data will be kept for 15 years. Final data will be shredded after 15 years.

References1. Kisch, A., et al., Being a haematopoietic stem cell donor for a sick sibling: Adult donors'

experiences prior to donation. Eur J Oncol Nurs, 2015. 19(5): p. 529-35.2. Korbling, M. and E.J. Freireich, Twenty-five years of peripheral blood stem cell

transplantation. Blood, 2011. 117(24): p. 6411-6.3. Wiener, L.S., et al., Sibling stem cell donor experiences at a single institution.

Psychooncology, 2008. 17(3): p. 304-7.4. Pillay, B., et al., The psychosocial impact of haematopoietic SCT on sibling donors. Bone

Marrow Transplant, 2012. 47(10): p. 1361-5.5. Labott, S. and A. Pfammatter, The influence of the donor-recipient relationship on related

donor reactions to stem cell donation. Bone Marrow Transplant, 2014. 49(6): p. 831-5.6. Leitner, G.C., et al., Regeneration, health status and quality of life after rhG-CSF-stimulated

stem cell collection in healthy donors: a cross-sectional study. Bone Marrow Transplant, 2009. 43(5): p. 357-63.

7. Garcia, M.C., et al., Motivations, experiences, and perspectives of bone marrow and peripheral blood stem cell donors: thematic synthesis of qualitative studies. Biol Blood Marrow Transplant, 2013. 19(7): p. 1046-58.

8. Hall, L.A. and B.S. Kiernan, Psychometric Assessment of the Autonomy and Relatedness Inventory: A Measure of the Quality of Primary Intimate Relationships. 1990.

9. Organization, W.H., Whoqol user manual: Programme on mental health. 1998.10. Simmons, R.G., S.D. Klein, and R.L. Simmons, Gift of life: The social and psychological

impact of organ transplantation. 1977.11. Switzer, G.E., et al., Understanding donors' motivations: a study of unrelated bone marrow

donors. Social science & medicine, 1997. 45(1): p. 137-147.12. Butterworth, V.A., et al., Psychosocial effects of unrelated bone marrow donation:

experiences of the National Marrow Donor Program. Blood, 1993. 81(7): p. 1947-1959.13. Karnofsky, D.A., The clinical evaluation of chemotherapeutic agents in cancer. Evaluation of

chemotherapeutic agents, 1949.14. Nater, U.M., et al., Stress-induced changes in human salivary alpha-amylase activity—

associations with adrenergic activity. Psychoneuroendocrinology, 2006. 31(1): p. 49-58.15. Rohleder, N. and U.M. Nater, Determinants of salivary α-amylase in humans and

methodological considerations. Psychoneuroendocrinology, 2009. 34(4): p. 469-485.16. Vineetha, R., et al., Usefulness of salivary alpha amylase as a biomarker of chronic stress

and stress related oral mucosal changes'a pilot study. 2014.17. Luecken, L.J. and L.C. Gallo, Handbook of physiological research methods in health

psychology. 2007: Sage Publications.18. Braun, V. and V. Clarke, Using thematic analysis in psychology. Qualitative research in

psychology, 2006. 3(2): p. 77-101.


synopsis - anzctr.org.au v… · web viewroyal brisbane and women’s hospital. department of...

Documents