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Psychosomatics 44:59-64, February 2003
© 2003 The Academy of Psychosomatic Medicine

Symptoms of Pain and Depression in Related Marrow Donors: Changes After Transplant

Grace Chang, M.D., M.P.H., Carol McGarigle, R.N., Danielle Koby, B.A., and Joseph H. Antin, M.D.

Received Dec. 3, 2001; revision received May 24, 2002; accepted May 30, 2002. From the Department of Psychiatry, Brigham and Women's Hospital; the Departments of Psychiatry and Medicine, Harvard Medical School, Boston; and the Dana-Farber Cancer Institute, Boston. Address reprint requests to Dr. Chang, Department of Psychiatry, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115; Gchang{at}partners.org (e-mail).


  ABSTRACT

 
TOP
 ABSTRACT
INTRODUCTION
 METHOD
 RESULTS
 DISCUSSION
 REFERENCES
 
Related or unrelated histocompatible marrow donors make it possible to offer hematopoietic stem cell transplants, the second most frequent solid organ transplant performed in the United States. About 20%–30% of donors are related to the recipient. Despite their importance, relatively little is known about related donors. The purpose of this prospective study is to describe changes in pain and depressive symptoms in 23 related marrow donors before and after marrow donation. Approximately 6 months after marrow donation, related marrow donors whose recipients died had significantly higher Beck Depression Inventory scores than did donors whose related recipients were living.


  INTRODUCTION

 
TOP
 ABSTRACT
 INTRODUCTION
METHOD
 RESULTS
 DISCUSSION
 REFERENCES
 
Histocompatible related or unrelated marrow donors make it possible to offer hematopoietic stem cell transplants, a lifesaving treatment for selected patients with aplastic anemia, acute and chronic leukemia, and lymphomas.1,2 Hematopoietic stem cell transplant is the second most frequently performed solid organ transplant in the United States, with the potential for growth and application to a variety of diseases. Approximately 20% to 30% of marrow donors are related to the recipient.3,4

Marrow donation occurs under general or spinal anesthesia. Marrow is aspirated from eight to 10 sites on each posterior and anterior iliac crest, requiring hundreds of needle punctures. When necessary, 10 to 12 aspiration sites along the sternum are also used in order to withdraw a total of 500 to 1500 ml of bone marrow. The amount of marrow withdrawn is based on the weight of the recipient. Postdonation pain has been compared to general postsurgical pain, which lasts for less than 1 week, with considerable interpatient variability.5

Despite the importance of marrow donors in the realization of hematopoietic stem cell transplants, they have received scant empirical investigation.6,7 Possible explanations include the infrequency of serious morbidity following marrow donation, the absence of long-term hematologic consequences for the donor, or that donor selection is made solely on the basis of histocompatibility with the recipient.8 Unrelated donors, however, have been the focus of more studies, perhaps because of the widespread assumption that family members are naturally motivated by the prospect of saving a loved one and that unrelated volunteers have clearly made unusual sacrifices.9–13

The altruism of unrelated volunteer marrow donors is well documented.14 Religious background, experiences with medical practices, and spousal attitudes to donation have been found to be important factors in the decision to donate.15–18 Unrelated donors derive no direct benefit from their donations but have been found to experience positive psychosocial outcomes after donation.19 Such positive outcomes include having high satisfaction or thinking of themselves as better people.20

The generally positive outcomes notwithstanding, a substantial minority of unrelated donors have less positive postdonation reactions, such as physical difficulty with donation and negative psychological reactions.21,22 Unrelated donors experience grief when the recipient dies but usually not guilt or responsibility.23

Some have recognized that the related donor will experience not only the procedural risks related to marrow donation but also many of the psychological and emotional distresses experienced by the transplant patient.5 Changes in family relationships and in the donors' reactions have been cited as possible consequences.6,24 The stresses imposed on the intrapsychic and interpersonal dynamics of the donor-recipient relationship have led to estimates that 20% of related marrow donors will experience adverse psychological reactions to donation.25

Wolcott et al.26 received 18 (50%) of 36 questionnaires sent to related marrow donors whose recipients survived more than 1 year after bone marrow transplantation. Information on 12 recipients was available, resulting in 12 (33%) matched donor-recipient pairs. The marrow donors generally had little emotional distress, high self-esteem, and a high degree of current life satisfaction. However, the current quality of their relationships with their marrow recipients was highly correlated with recipient health status and psychosocial variables. Four (22%) of the 18 donors reported physical problems they attributed to marrow donation, such as back pain and erectile dysfunction.26

Other investigators have attempted to characterize related donor pain. Hill et al.5 studied the time course and intensity of postoperative pain in 30 related donors; there was a 40% attrition rate in the original sample of 50. Donors used analgesic medication (315 mg acetaminophen with 30 mg codeine) for a mean of 3.3 days (SD=0.5) after marrow harvesting and reported less than complete pain relief. Male donors tended to report more pain and used more analgesic than female donors.5

In a previous study,27 our group compared 41 unrelated and 36 related marrow donors pre- and postdonation, with an overall follow-up rate of 97%. The principal finding was that related marrow donors reported significantly more acute physical pain in the 2-week period after donation than unrelated donors (odds ratio=7.63, 95% confidence interval=2.74–23.01; p=0.0001). It seemed improbable that intraoperative events alone would have accounted for the greater pain reported by related donors. Of note, the related donors had higher Beck Depression Inventory scores both before (p=0.0085) and after (p=0.005) marrow donation than did the unrelated volunteers. However, the significance and persistence of the pain experienced by the related marrow donors, as well as their higher Beck Depression Inventory scores, remain to be examined, since there was only one postdonation follow-up.

Another study of 12 (27%) of 45 potential related marrow donors interviewed within 1 year of donation found that all would repeat the experience and all felt deep personal satisfaction and gratitude for the opportunity to donate.7 However, stressful aspects included unanticipated pain after the procedure, negative transplant outcomes, and changes in relationships with the bone marrow recipients' family.

Switzer et al.9 examined the effects of bereavement on adult sibling marrow donors' psychological well-being and reactions to donation 1–2 weeks before donation, 1–2 weeks after donation, and 1 year after donation in a panel of 44 donors (58%) from an initial study group of 76. At the 1-year postdonation assessment, bereaved donors had higher self-esteem, were happier, and reported greater life satisfaction than did donors with living sibling recipients.

Despite these intriguing findings, much remains to be known about related marrow donors. As with many rapidly developing medical advances, the understanding of psychosocial consequences lags behind technical knowledge.28 The lack of information is further exacerbated by the challenges of studying related marrow donors, since the few previously published studies have had small group sizes with high attrition rates, have relied on single retrospective reports, or did not measure pain or depressive symptoms longitudinally.5,7,26

The purpose of this prospective study was to characterize the extent and duration of pain and depressive symptoms experienced by a consecutive group of related marrow donors. The donors were asked to complete questionnaires about pain and depression before marrow donation and twice afterwards. The impact of recipient outcome on donors' reports of pain and mood was also examined. This study was reviewed and approved by the Institutional Review Board of the Brigham and Women's Hospital in Boston.


  METHOD

 
TOP
 ABSTRACT
 INTRODUCTION
 METHOD
RESULTS
 DISCUSSION
 REFERENCES
 
For an 18-month period beginning in April 1999, a consecutive (one after another) group of medically cleared related marrow donors were invited by the bone marrow transplant coordinator (C.M.) to participate in the study. No peripheral stem cell donors were invited to participate. All subjects were asked to complete self-report measures at three times: Phase 1, just before marrow donation; Phase 2, within 2 weeks after marrow donation; and Phase 3, within 6 months after marrow donation.

Questionnaires at each of the study phases consisted of the Beck Depression Inventory,29 a 21-item self-report measure of depression, and measures of pain. The Beck Depression Inventory is a widely used measure of depressed mood with a coefficient alpha estimate of reliability of 0.93 for nonclinical samples.30 Measures of pain included the pain location and pain description sections from the McGill Pain Questionnaire,31 the Numerical Rating Scale of Pain,32 and the Box Scale of Pain.33 For pain location and description, the subject is asked to indicate on a drawing of a human body the location of pain and whether or not the pain is internal or external. The Numerical Rating Scale of Pain, which rates pain from 0 (no pain) to 100 (pain as bad as it can be), has been demonstrated to be the most practical index of pain measurement. The Box Scale of Pain, which rates pain on a scale from 0 (no pain) to 10 (pain as bad as it can be), has been determined to be the most useful clinical index of pain intensity among postoperative patients.33

In addition, open-ended questionnaires were used to ask subjects for some specific pre- and postdonation information. Before donation, subjects were asked about their demographic background, relationship to the marrow recipient, current medical problems, history of pain, and time lost from work because of pain. After donation, subjects were asked to indicate time off from work or usual activities because of marrow donation, need for medical care after marrow donation, and knowledge of transplant outcome.

Data Analysis
Simple descriptive statistics summarizing subject characteristics and pre- and postdonation measures were calculated. Results are reported as percentages or means with standard deviations. Categorical data were compared by using Fisher's exact test. One-way analysis of variance (ANOVA), repeated-measures design, was used for serial measures of pain and Beck Depression Inventory scores. Scores on pain measures and the Beck Depression Inventory for donors whose recipients died were compared with those whose recipients were alive by the Wilcoxon rank sum test, a nonparametric analogue to the t test.34 All analyses were conducted with SAS 8.e.35


  RESULTS

 
TOP
 ABSTRACT
 INTRODUCTION
 METHOD
 RESULTS
DISCUSSION
 REFERENCES
 
All 25 (100%) related marrow donors invited to participate in the study agreed. Of these, 23 completed marrow donation. These 23 subjects who donated marrow will serve as the basis of this report. Donors completed the predonation Phase 1 questionnaires an average of 10 days (SD=24) before donation, when they also offered consent to participate in this study.

The mean age of the marrow donors was 37.6 years (SD=11.7). About half were male (52%, N=12), and most (91%, N=21) were siblings of the recipient. Most donors were single, being never married (43%, N=10), divorced (9%, N=2), or widowed (4%, N=1); 43% (N=10) were currently married. The Hollingshead two-factor index of social position was calculated for each participant: 17% (N=4) were from Class I, 26% (N=6) from Class II, 9% (N=2) from Class III, 30% (N=7) from Class IV, and 17% (N=4) from Class V.

Thirteen (57%) completed Phase 2 questionnaires, at average of 21.3 days (SD=13.7) postdonation. Fifteen (65%) completed Phase 3 questionnaires, at an average of 204 days (SD=73) postdonation. Eleven (48%) completed questionnaires for all three phases. Six (26%) completed only the initial assessment; the overall response rate was not associated with transplant recipient outcome (p=0.37, Fisher's exact test, two-tailed).

Predonation measures of marrow donors indicated that most did not have current medical problems (65%, N=15), and that about one-quarter (26%, N=6) had lost any time recently from work because of pain. The mean number of workdays lost because of pain was 5.7 (SD=19.0). The mean numerical rating of predonation pain was 20.5 (SD=31.0, range=0–90). The mean numerical rating of predonation pain was correlated with another measure of predonation pain, the Box Scale (r=0.92, df=21, p<0.0001). The mean Box Scale score was 1.7 (SD=2.6). The eight subjects with predonation pain had chronic conditions such as "osteoarthritis" or "old sports injuries." Current medical problems were not correlated with either measure of predonation pain but were correlated with subject age (r=0.47, df=21, p=0.02). The mean Beck Depression Inventory score predonation was 4.3 (SD=5.9).

Subjects took an average of 3.9 days (SD=2.6) off from usual activities after marrow donation. The mean Beck Depression Inventory and pain scores at each phase are summarized in Table 1. Results for the 11 participants with complete data from all three phases were analyzed by using one-way ANOVA, repeated-measures design. These analyses revealed no statistically significant changes over time for these measures.


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TABLE 1. Depression and Pain Symptom Scores Among 23 Subjects Donating Bone Marrow to a Relative



All transplant recipients were alive in the first month after marrow donation, but by the time of final follow-up, 12 had died. Marrow donors whose relatives had died had significantly higher Beck Depression Inventory scores than those whose recipient relatives were alive (Table 2). The changes in mean Beck Depression Inventory scores from initial measurement predonation to the last measurement were different as well. On average, scores for related donors with deceased recipients increased, whereas the mean Beck scores for donors with living relative recipients decreased (Table 2). Although the results were not significant, higher scores for reports of current pain, as measured by the Numerical Rating Scale of Pain and Box Scale of Pain, were seen in the marrow donors with deceased recipient relatives as well.


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TABLE 2. Depression and Pain Symptom Scores at Final Follow-Up Evaluation Among Subjects Donating Bone Marrow to a Relative, by Outcome of Marrow Recipient




  DISCUSSION

 
TOP
 ABSTRACT
 INTRODUCTION
 METHOD
 RESULTS
 DISCUSSION
REFERENCES
 
Marrow donation is not likely to be a straightforward process for either related or unrelated donors, despite the potential positive impact of their donation. Related donors may have additional challenges imposed, since they have a seriously ill family member as well. This study of related marrow donors suggests that the death of the recipient is associated with higher Beck Depression Inventory scores, but not measures of physical pain, when compared with those related donors whose recipients were still alive 6 months after transplant.

Potential limitations to the generalizability of these findings include the small study group size, the lack of a comparison group, and the 48% completion rate for all three sets of questionnaires. The small size and completion rate appear to be typical for other attempts to study related marrow donors and may reflect the difficulty in engaging subjects, who may be stressed or preoccupied by other matters. No potential participants refused outright to join the study. It is also possible that no single transplant center will be able to accrue an adequate sample size in a reasonable time frame, and research linkages with other programs may be necessary. A comparison group would be helpful in future efforts. Depending on the question of interest, the comparison group might consist of other transplant recipient nondonor relatives (e.g., subsequent depression) or unrelated donors (e.g., postdonation pain).

The higher Beck Depression Inventory scores for related donors with deceased recipients approximately 6 months after donation may reflect a transient reaction to their loss. Indeed, Switzer et al.9 found that at a 1-year postdonation assessment, bereaved donors had higher self-esteem, were happier, and reported greater life satisfaction than did donors with living sibling recipients. However, Switzer et al.9 did not use a specific measure for depression but rather a six-item scale of global well-being.

In general, the physically healthy bone marrow donor has not received much psychological attention, particularly if the donor is related to the recipient.8 Yet, it is likely that it is the very nature of the relationship the related donor has to the recipient that renders the process of donation more complicated. Psychological and immunological changes have been found in the nondonor spouses/partners of individuals undergoing bone marrow transplant.36 Thus, it is hardly surprising that donors related to deceased recipients should experience more depressive symptoms, as this study suggests. After all, the relationship to the recipient does not protect the related donor from the pain experienced after donation of either marrow or peripheral blood stem cells.5,27,37,38 Just as transplant recipients have a program of scheduled pre- and posttransplant appointments, related donors may benefit from a similar course with professionals who are able to evaluate them for adverse physical and psychological reactions. Related or unrelated, marrow donors are the other transplant patients.27


  ACKNOWLEDGMENTS

 
This study was supported in part by a grant from the Aplastic Anemia Foundation of America, New England Chapter, to Ms. McGarigle and a National Institute on Alcohol Abuse and Alcoholism grant (AA-00289) to Dr. Chang.


  REFERENCES

 
TOP
 ABSTRACT
 INTRODUCTION
 METHOD
 RESULTS
 DISCUSSION
 REFERENCES
 

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