The Impact of Hematopoeitic Stem Cell Transplantation on Primary Caregiver Level of Burden and Distress
Conditions: Depression, Anxiety, Fatigue, Distress
Sponsor: Northside Hospital, Inc.

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NORTHSIDE HOSPITAL 
 
 
 
THE IMPACT OF HEMATOPOIETIC STEM CELL TRANSPLANTATION ON 
PRIMARY CAREGIVER LEVEL OF BURDEN AND DISTRESS 
 
 
 
 
Principal Investigators:  
Dawn Speckhart, PhD 
 
  
 
 
 
Associate Investigators: 
H. Kent Holland, MD 
 
  
 
 
Scott R. Solomon, MD  
 
  
 
 
Asad Bashey, MD, PhD 
 
  
 
 
Lawrence E. Morris, Jr, MD 
 
  
 
 
Melhem Solh, MD 
                                                                         
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
 
SCHEMA………………………………………………………. 
3 
 
1.0 
OBJECTIVES…………………………………………………. 
4 
 
2.0 
BACKGROUND AND RATIONALE……………………….. 
4 
 
3.0 
DRUG INFORMATION……………………………………… 
5 
 
4.0 
PATIENT SELECTION……………………………………… 
5  
 
5.0 
TREATMENT PLAN………………………………………… 
6 
 
6.0 
ADVERSE EVENT REPORTING…………...……………… 
6 
 
7.0 
RISKS AND TOXICITIES…………………………………….. 7 
 
8.0 
STATISTICAL CONSIDERATIONS………………………… 7 
 
9.0 
REFERENCES…………………………………………………. 7 
 
Appendices:  
 
Appendix A: BSI-18 
Appendix B: BFI  
 
Appendix C: BPI 
 
Appendix D: Burden Interview 
 
Appendix E: Demographic Form 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Treatment Schema  
 
 
 

 
 
 
 
 
Pre-BMT 
Day 0 
Day 71 
Day 301 
Day 3652 
Patient 
BSI-18 
BFI 
BPI 
BSI-18 
BFI 
BPI 
BSI-18 
BFI 
BPI 
BSI-18 
BFI 
BPI 
BSI-18 
BFI 
BPI 
Caregiver 
Demographics 
BSI-18 
BFI 
Burden Interview 
BSI-18 
BFI 
Burden Interview 
BSI-18 
BFI 
Burden Interview 
BSI-18 
BFI 
Burden Interview 
BSI-18 
BFI 
Burden Interview 
1  Assessment can be done +/- 3 days 
2 Assessment can be done +/- 7 days 
 
 
 

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1.0 OBJECTIVES 
 
Primary Objectives: 
 
1.1 To investigate the level of distress and feelings of burden in caregivers of HSCT patients.  
 
Secondary Objectives: 
 
1.2 To investigate the impact of patient distress, fatigue and pain on the level of caregiver 
distress and burden.   
 
1.3  To investigate the impact of caregiver distress and burden on overall patient survival and 
length of patient hospitalization.   
 
1.4 To identify common characteristics of caregivers who report significantly more feelings of 
burden or distress.   
 
2.0 BACKGROUND 
 
Hematopoietic stem cell transplant (HSCT) is an established treatment for certain hematologic 
malignancies1. The process of undergoing HSCT is intense and time consuming.  Patients and 
their caregivers are required to commit to several months of treatment and close follow-up.  At 
our institution, the Blood and Marrow Transplant Program at Northside Hospital, the transplant 
process includes frequent, if not daily, visits to the clinic, and at times lengthy hospital stays for 
the patient.  Our program requires patients to have a full-time caregiver to assist them with 
transportation, treatment compliance, nutritional intake and emotional support.  Patients are not 
allowed to be alone, go to public areas, or independently manage their medications.  Patients are 
most commonly out of work for extended periods of time.  The need for a caregiver places an 
extra burden on the patient and their loved ones, as caregivers are not able to work full time 
while caring for an HSCT patient.  Many studies have looked at the quality of life and various 
psychological symptoms in patients undergoing HSCT.   Studies have analyzed the impact of 
HSCT on patient health related quality of life (HRQOL) during and after HSCT.  However, little 
is known about the impact of HSCT on spouses/partners or other primary caregivers.  
 
The process of serving as a caregiver for a loved one going through HSCT is rigorous and 
stressful.  Much of the psychosocial support that exists in transplant centers focuses on the 
patients with little support for the caregivers.  Friends and family also tend to place emphasis on 
the patient undergoing the treatment and give less attention to the patient’s caregiver.  Even with 
the presence of community support groups and education from the transplant programs, 
caregivers typically report experiencing high levels of distress.  Caregivers often express feeling 
the weight of the world on them, as they are left to worry about everything outside of transplant 
(i.e. finances, child care), in addition to being very concerned with the patient’s health.  They 
feel a sense of responsibility for the patient improving medically.   
 
More recently, transplant programs have begun to identify needs of HSCT caregivers.  
Researchers have begun to recognize caregivers as an important and often overlooked participant 

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in the HSCT process.  The current literature on HSCT caregivers suggests that caregivers for 
HSCT patients do report feeling stressed, exhausted emotionally and physically, and in need of 
support2, 3, 4.  One study identified high levels of stress and depression pre-transplant5.   A 2004 
study by Gaston-Johansson6 found that primary caregivers of patients with breast cancer 
scheduled for BMT experience fatigue, anxiety, burden of care, and low quality of life.   
 
Due to these previous findings, it was clear that level of burden, fatigue and distress were 
essential properties to be measured in HSCT caregivers.  Each of these areas will be measured by 
a specific, psychometrically sound instrument.  The Burden Interview, The Brief Fatigue 
Inventory, The Brief Pain Inventory and the Brief Symptom Inventory-187, 8, 9, 10, 11, 12, 13, 14 were 
selected due to there previous use in oncology settings.   
 
The purpose of this study is to examine the impact of HSCT on the caregiver’s level of burden, 
depression, anxiety, somatic symptoms, fatigue and overall distress.  It will also examine if 
caregiver burden leads to an increase in the patient’s hospital utilization and overall outcome.  In 
addition, we hope to identify these caregiver symptoms as they relate to the patient’s overall 
functioning.  Therefore, each patient will also complete self-report measures in order to assess if 
the patient’s level of distress impacts the caregivers’ functioning.  The patients will complete 
self-report measures assessing symptoms of psychological distress, pain and fatigue and these 
scores will be matched to their particular caregiver. 
 
 
3.0 DRUG INFORMATION 
 
There are no drugs associated with this study. 
 
4.0 PATIENT SELECTION 
 
4.1 Patient eligibility 
 
4.1.1 Any patient undergoing autologous or allogeneic HSCT at The Blood and Marrow 
Transplant Program at Northside Hospital will be eligible.   
4.1.2 Patients must have a single primary caregiver.   
4.1.3 Patient must be willing to comply with all assessments as outlined in the protocol.   
4.1.4 Patient must be willing to sign informed consent. 
 
4.2 Caregiver eligibility 
       
4.2.1 Must be the primary caregiver for an autologous or allogeneic HSCT patient at The 
Blood and Marrow Transplant Program at Northside Hospital.   
4.2.2 Caregiver must be willing to comply with all assessments as outlined in the protocol.   
4.2.3 Caregiver must be willing to sign consent.    
 
 
 
 
 
 

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5.0 TREATMENT PLAN  
 
Pre-BMT 
Patient Completes: BSI-18, BFI, BPI  
 
Caregiver Completes: Demographic Form, BSI-18, BFI, Burden Interview 
 
 

 
Days 0, 7, 30 and 365 
Patient Completes: BSI-18, BFI, BPI  
 
Caregiver Completes: BSI-18, BFI, Burden Interview 
 
 
Pre-BMT 
Day 0 
Day 73 
Day 303 
Day 3654 
Demographics1 
X  
 
 
 
 
BSI-18 
X 
X 
X 
X 
X 
BFI 
X 
X 
X 
X 
X 
BPI2 
X 
X 
X 
X 
X 
Burden Interview1 
X  
X  
X  
X  
X  
1caregiver only 
2patient only  
3assessment to be done +/- 3 days 
4assessment to be done +/- 7 days 
 
 
6.0 ADVERSE EVENT REPORTING 
 
Adverse events are further defined as “Any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not necessarily have 
to have a causal relationship with this treatment.” 15 
 
Patients will be monitored by the investigators and data maintained by the Clinical Research 
Program.  All Adverse Events will be graded with the Common Terminology Criteria for 
Adverse Events (CTCAE) Version 3.0.  
 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf 
 
Due to the non-treatment nature of this protocol, there are not expected to be any adverse events. 
However, should a patient experience an adverse event that is specifically related to participation 
in this study, the following reporting criteria will apply.  Patients will be followed through Day 
365 for protocol-related adverse events.   
 
6.1 Procedure for reporting Serious and Unexpected Adverse Events 
 
Serious Adverse Events will be reported by telephone or email to the Institutional Review Board 
within 24 hours of notification of event.  Written report will follow within 10 working days.  
Serious adverse events will be reported for a period of one (1) year post-transplant.   
 
6.2  
Definition of Serious and Unexpected Adverse Events: 

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Serious Adverse Events are defined as one of the following: 
a. 
Death  
b. 
Life-Threatening  
c. 
Hospitalization (initial or prolonged)  
d. 
Disability 
e. 
Congenital Anomaly  
f. 
Requires Intervention to Prevent Permanent Impairment or Damage 
 
Unexpected is defined as: 
Not previously reported with the agents/devices or procedures being undertaken.  Symptomatically 
and pathophysiologically related to known toxicity but differs because of greater severity than 
previously reported. 
 
7.0 RISKS and TOXICITIES 
 
7.1 There are no expected risks associated with participation in this study.  However, there may 
be an indirect or direct increase in psychological distress related to the completion of the 
psychological measures.  Patients and caregivers will be monitored per programmatic protocol 
for any increases in psychological distress and these symptoms will be managed according to 
programmatic standards.  All participants will be asked to contact the principal investigator, who 
is a licensed psychologist, if they experience an increase in psychological distress.   
 
8.0 STATISTICAL CONSIDERATIONS/DATA ANALYSIS 
 
8.1 We will plan to accrue 50 autologous and 50 allogeneic patient/caregiver dyads. This number 
of patients will be sufficient to perform an initial analysis to examine levels of distress and 
associated outcome variables. We expect that patients will be accrued over 1-2 years. 
 
8.2  Data analysis will be performed on the information gathered to evaluate the impact of HSCT 
on the caregiver’s level of burden, depression, anxiety, somatic symptoms, fatigue and overall 
distress.  It will also examine if caregiver burden leads to an increase in the patient’s hospital 
utilization and overall outcome.  In addition, we hope to identify these caregiver symptoms as 
they relate to the patient’s overall functioning.  The analysis will include t-tests to look at 
correlations, as well as more complex statistical procedures (e.g., manova, and multiple 
regression analyses) to identify relationships between variables.   
 
9.0 REFERENCES 
 
1) Malden M. Thomas' Hematopoietic Cell Transplantation. 3rd ed. Blackwell Publishing; 
2004. 
2) Aslan O, Kav S, Meral C, Tekin F, Yesil H, Ozturk U, Bulut Z, Anaboifo A, Dover M, 
Yazar B. Ness of lay caregivers of bone marrow transplant patients in Turkey: a 
multicenter study.  Cancer Nursing, 29 (6): E1-7, 2006.  

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3) Boyle D, Blodgett L, Gnesdiloff S, White J, Bamford AM, Sheridan M, Beverisge R. 
Caregiver quality of life after autologous bone marrow transplantation. Cancer Nursing, 
23 (3): 193-203, 2000. 
4) Foxall MJ, Gaston-Johansson F. Burden and health outcomes of family caregivers of 
hospitalized bone marrow transplant patients. Journal of Advanced Nursing, 24 (5): 915-
23, 1996.  
5) Harris, Margaret. Uncertainty and caregiver burden in family caregivers of HSCT 
patients. Oral presentation at the Transplant Nursing Conference BMT Tandem Meetings, 
February, 2009. 
6) Gaston-Johansson F, Lachica EM, Fall-Dickson JM, Kennedy MJ. Psychological distress, 
fatigue, burden of care, and quality of life in primary caregivers of patients with breast 
cancer undergoing autologous bone marrow transplantation.  Oncology Nursing Forum, 
31 (6): 1161-9, 2004.  
7) Zarit SH, Zarit JM. The memory and behavior problems checklist and the burden 
interview – Univeristy Park, PA: Penn State Gerontology Center, 1990. 
8) Mendoza T, Wang XS, Cleeland CS, Morrissey M, Johnson BA, Wendt JK, Huber SL. 
The rapid assessment of fatigue severity in cancer patients: use of the Brief Fatigue 
Inventory. Cancer 1999; 85: 1186-96.  
9) Chang YJ, Lee JS, Lee CG, Lee WS, Lee KS, Bang SM, Wang XS, Mendoza TR, 
Cleeland CS, Yun YH. Assessment of clinical relevant fatigue level in cancer. Support 
Care Cancer 15(7): 891-896, 2007. 
10) Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann 
Acad Med Singapore 23(2): 129-138, 1994.  
11) Cleeland CS. Measurement of pain by subjective report. In: Chapman CR, Loeser JD, 
editors. Advances in Pain Research and Therapy, Volume 12: Issues in Pain 
Measurement. New York: Raven Press; 1989. p. 391-403.  
12) Shi Q, Wang XS, Mendoza TR, Pandya KJ, Cleeland CS. Assessing persistent cancer 
pain: a comparison of current pain ratings and pain recalled from the past week. J Pain 
Symptom Manage, in press.  
13) Zabora, James; BrintzenhofeSzoc, Karlynn; Jacobsen, Paul; Curbow, Barbara; 
Piantadosi, Steven; Hooker, Craig; Owens, Albert; Derogatis, Leonard (2001). A new 
psychosocial screening instrument for use with cancer patients. Psychosomatics: Journal 
of Consultation Liaison Psychiatry, 42(3), 241-246.  
14) Asner-Self, Kimberly K.; Schreiber, James B.; Marotta, Sylvia A. (2006). A cross-
cultural analysis of the Brief Symptom Inventory-18. Cultural Diversity & Ethnic 
Minority Psychology, 12(2), 367-375.  

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15) Expert Working Group (Efficacy) of the International Conference on Harmonisation of 
Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). 
(August 25, 2007).  “Guideline for Industry – Clinical safety data management: 
definitions and standards for expedited reporting.” (PDF). FDA Center for Drug 
Evaluation and Research.