Quality of life in adult bone marrow transplant patients: Beyond the first year

Quality of Life in Adult Bone Marrow Transplant Patients: Beyond the First Year Marie Whedon and Betty R, Ferrell When I look around the waiting room and see so many people that are really sick or really worried about what's going to happen to them, I feel guilty taking up my doctor's time. But I have questions t o o . . . Why do I still have these physical problems and thinking problems this many years after my transplant? -Statement of a 4-year bone marrow transplant survivor

IGNIFICANT numbers of successful syngeneic, allogeneic, and autologous bone marrow transplants (BMT) have been performed worldwide for malignant and nonmalignant diseases since the first reported successful cases in 1968 and 1969. ~-3 It has been estimated that there are currently more than 2,000 marrow transplant patients surviving between 5 and 20 years. 4 As a result, patients and health care providers have broadened their interest and concern beyond the length of survival to the quality of life (QOL) after survival. Among cancer treatment providers in general, and transplant teams in particular, there is a growing appreciation and consensus that the ultimate success of cancer treatment will be determined not only by absence of disease and other long-term physical sequela, but by patient-reported

S

Q O L . 4-6

Information about the nature of posttransplant survival and QOL is important in patient counseling and informed consent pretransplant and in evaluating outcomes after different types of conditioning therapy. Recent literature7-9 has focused on From the Dartmouth-Hitchcock Medical Center, Lebanon, NH; and the City of Hope National Medical Center, Duarte, CA. Marie Whedon, MS, RN, OCN: Hematology/Oncology Clinical Nurse Specialist, Dartmouth-Hitchcock Medical Center; Betty R. Ferrell, RN, PhD, FAAN: Associate Research Scientist, City of Hope National Medical Center. This work was supported in part by Grant No. CA23108 from the National Cancer Institute, a Special Institutional Grant (SIG 19) from the American Cancer Society, and the 1992 Oncology Nursing Foundation~Wyeth New Investigators Grant. Address reprint requests to Marie Whedon, MS, RN, OCN, Hematology/Oncology Clinical Nurse Specialist, DartmouthHitchcock Medical Center, 1 Medical Center Dr, Lebanon, NH 03756. Copyright 9 1994 by W.B. Saunders Company 0749-2081/94/1001-000655.00/0

42

long-term survival post-BMT and has focused on the relationship between the concepts of survivorship and QOL. This understanding can assist the care provider in defining rehabilitation and counseling needs of BMT long-term survivors. Using a QOL framework, 7'8 this review will provide a brief summary of the nature of the longterm effects observed in adults that occur or persist 1 year after BMT4'6'9-t9 and reports on post-BMT QOL. 7'8'2~ An analysis of the QOL reported in 780 adult survivors from 15 separate studies7'2~ is synthesized into a relevant, patient-focused perspective and contributes to the growing literature on survivorship by providing a perspective on the adult BMT survivor beyond the 1-year milestone. ANALYSIS OF LONG-TERM SURVIVAL USING A QOL MODEL

Based on previous QOL research and surveys of a sample of 119 long-term BMT survivors, Ferrell and colleagues proposed a model of the impact of BMT on patient's QOL. 7 The QOL/BMT model (Fig 1) depicts the impact of transplant and survivorship on four domains, including physical wellbeing and symptoms, psychological well-being, social well-being, and spiritual well-being. Viewing this model in total, one sees survivor's QOL as a series of interrelationships between domains. A disruption in one domain may influence other domains and QOL in general. For instance, cataracts can affect physical well-being but may also effect the ability to return to former employment (social well-being) and coping style (psychological wellbeing). Viewing effects of BMT from a broader QOL perspective provides the health care provider with an appreciation of the need for a comprehensive assessment of the survivor's QOL and rehabilitation needs. Long-term effects of BMT, also known as delayed or late complications, are defined as phenomenon that result from bone marrow transplantation and occur or continue longer than 100 days post-BMT. 1~ The time between 100 days and 1 year is unique and distinctly different from the subsequent years of survivorship. It is marked by many physical effects and frequent checkups and is Seminars in Oncology Nursing, Vol 10, No 1 (February), 1994: pp 42-57

BMT:

QUALITY

OF LIFE

43

Physical Well-Being & Symptoms 9 9 9 9 9 9 9

PS•ClhOloglcal

Strength and Stamina Functional ActMtles Visual Dbtm'bmm~CaOncU Recurrent Colds InfertJlf~ Coping with Chromic GVHD Nutrition

9 A,u~,ty 9 Fear of Recnrrmce 9 Chsnlpd Priarnl~ 9 Cognition/Attention 9 Nernmky

9 Second ~ 9 Coplng with Survival

?

1

Social Well-Being 9 Appearance 9 Financial Burden 9 Rolesand Relstiemhlps 9 An*ecflon/~xlml Function 9 Caregiver Burden 9 Lelsnee Activities 9 Return to Work

Spiritual Well-Being

4-

F i g 1.

Physiological long-term effects can be considered in the domain of physical well-being and symptoms. This aspect of the posttransplant survivorship period is objectively recorded by many transplant centers and is perhaps the most extensively described. A growing body of literature has provided in-depth insight into the undesirable physiological effects that may occur after marrow transplantation. 4'6'9~9 Many of these reviews address both the immediate (months) and longer term (years) effects. The highest number of symptoms occur during the first year. However, after that time, many physiological effects will have resolved (with the exception of those patients with chronic graft-versus-host disease

9 Strtngthtned Belief 9 Hope

[cGVHD]) .4,6,11,16

. ~nt~r 9~usJmi~,

Physiological effects can be categorized by etiology: (1) from the transplant (eg, cGVHD): (2) from the damage caused by chemotherapy, radiation therapy, and/or immunosuppressive agents (including secondary malignancies): or (3) from the original disease (primarily relapse). However, a more "user-friendly" framework for survivors and their health care providers is that of a systems approach: describing the problems specifically by organ system or syndrome (cGVHD). Table 1 updates and comprehensively summarizes by system only those physiological effects that commonly persist or occur after the first year of BMT. As the recovery trajectory of the post-BMT period is more fully defined, it may be more helpful for patients and health care providers to view the first year post-BMT as an acute recovery period in the physical domain. In this view, one can more helpfully describe or separate physical effects that may persist after treatment requiring prolonged recovery (immunosuppression and frequent colds) from those that are not expected to develop until after a year or more (pulmonary problems or second malignancies). The latter issues can become part of an exit interview process in which health care providers discuss the purpose and importance of follow-up care and what type of testing the survivor might routinely expect to undergo at specified intervals (Table 2). Frequently long-term effects are caused by graft-versus-host disease (GVHD) and its treatment. These patients unfortunately begin a crusade of physiological effects that will remain chronic

9 Inner Strength II II

printed

PHYSICAL WELL-BEING

l-Being

BMT affects the dimensions of quality of with p e r m i s s i o n . 7)

life. (Re-

more accurately viewed as a continuation of acute posttreatment recovery. During that time, the patienrs status is often very labile in all QOL domains. Beyond the first year, many of the effects of BMT will resolve, yet some may continue as chronic health problems. In this sense, the life course of a BMT survivor could be characterized as a tightrope walk because the individual is moving cautiously forward through each month of survival beyond the state of having chronic cancer, but physically and psychologically, is not quite reaching an identity of cure for some time. Long-term effects of BMT are multidimensional and result from a combination of the delayed physical effects of multimodal therapy, being labeled as a cancer patient (survivor), confronting a threatening illness, and facing an uncertain future disease course. 23 Some survivors are now surpassing the 20-year mark. A useful QOL model must allow for assessment of QOL across the trajectory of survivorship from acute (< 1 year) through extended (1 to 5 years) to permanent (beyond 5 years) survival. 34 In the following discussion, each QOL domain will be considered separately, focusing on the consequences in each that occur after the first year.

WHEDON AND FERRELL

44

Table 1. Post-BMT Physical Effects in Adults That Occur or Remain After 1 Year Long-Term Effect Chronic GVHD Effects

Incidence (%) 33-64

Comments

ReferenceNo.*

Skin

79

Lower incidence in matched, higher incidence in unrelated. Lichenoid and scleroderma.

4, 16.

Liver

73

Occasional progression to biliary cirrhosis.

4, 15, 16, 18.

Oral

72-80

Oral sicca may lead to dental decay. Oral sensitivity common.

4, 16, 18.

Ophthalmic

38-47

15, 16, 18+

Sicca, grittiness, discomfort, photophobia.

4, 13, 16, 18.

Intestinal

16

Diarrhea, steatorrhea.

4, 13, 16, 18, 37.

Myofacial

11

Myostitis, polyarthritis, limited range of motion.

4, 13, 15, 16, 18.

Pulmonary

11

Obstructive defects, bronchiolitis obliterans.

4, 16, 18.

Esophogeal

6

Strictures.

4, 16, 18.

GI/nutritional

28 18 8

Weight loss. Xerostomia. Anorexia.

37.

Myasthenia gravis, autoimmune thrombocytopenia, vaginal sicca.

4.

Other Non-GVHD Effects

Pulmonary Restrictive disease

7-20

4, 9, 11.

Obstructive airway

5-10

4, 9, 11.

Genitourinary Reproductive

Men Women Bladder

Some normal pregnancies have resulted in women, and fathered by men postBMT sterility. 90-100 90-100 Reported.

4,11,13,15,36.

Sterility, ovarian failure, no menses, early menopause. Bladder shrinkage, s/p. Hemmorhagic cystitis.

Renal Radiation nephritis Renal insufficiency

Reported. 20

Begins 1 year or later.

4,15. 15, 17.

Neurological Visual/cataracts

Neuropsychological

Thyroid function Aseptic necrosis of the bone

19-75

Reported.

15-65 10

Lowest incidence with chemotherapy only, highest with single-dose TBI, also from steroid therapy. Memory, attention, concentration difficulties, slowed cognitive processing. Hypothyroidism usually due to TBI, reduced incidence in fractionated dose. Due to high-dose corticosteroid treatment for acute GVHD.

4, 15.

4, 36, 38.

4, 11, 15. 4, 16.

Abbreviation: S/P, status post, TBI, total body irradiation. * Only reviews and recently reported primary sources that update the comprehensive previously published reviews are listed,

BMT: QUALITY OF LIFE

Table 2. Recommendations for Follow-up Evaluations to Consider After BMT Chronic GVHD evaluation

Disease-appropriate laboratory studies (ie, CBC, immunological studies, liver function, renal function)

Disease-appropriate imaging studies Bone marrow aspiration and biopsy

Fertility/hormonal evaluation (LH/FSH levels, sperm count, testosterone levels) Nutritional evalu~ion Csrdiopulmonary function

Mobility/exercise tolerance Neuropsychological function Visual acuity Psychosocial evaluation Occupational/vocational evaluation Abbreviations: CBC, complete blood count; LH/FSH, luteinizing hormone/follicle-stimulating hormone. Data from Buchsel, 1991~8 and Sullivan et al, 1991.~s

symptoms. GVHD occurs exclusively in allogeneic marrow recipients and more frequently in recipients with less well-matched donors. The incidence is 33% in patients with matched sibling donors, 49% in those with nonidentical family member donors, and 64% in recipients of unrelated donors. Furthermore, the greater the degree of mismatch, the earlier in the post-BMT period cGVHD is likely to occur (day 133 in recipients of unrelated marrow v day 201 in recipients of related marrow). It rarely occurs after day 500.16 The overall probability of occurrence is 42% to 46% in those survivors over age 20 versus approximately 13% in patients less than 9 years) 6 Total body irradiation (TBI) is recognized as the aspect of treatment that has the most extensive long-term morbidity. As a result, attempts have been made to eliminate it, when possible, from BMT preparative treatment regimens. Most notable effects include endocrine dysfunction (growth, thyroid, and reproductive effects), 15'16 visual changes (cataracts), 11A5 cognitive dysfunction,35 and second cancers. 19 Combinations of factors are responsible for a variety of other significant physical effects. Physiologically-based problems with sexuality and fertility are a significant source of distress in some survivors. Chemotherapy and radiation each play a rote in the reproductive effects, which vary in severity but often result in loss of ovarian function and spermatogenesis. ~5 Those men and women who underwent treatment before fulfilling their re-

45

productive life goals often mourn this loss. Occasionally return of reproductive function has been reported, and normal, healthy children have been born to previously treated women and fathered by male BMT survivors. 11,13,15,36 Women who experience changes in vaginal lubrication and men who experience ejaculatory problems may have difficulties in maintaining a sexually satisfying, intimate relationship or initiating a new one. Clearly, these physical effects can interfere with other QOL domains, specifically psychological and social well-being. Fatigue27'28 and nutritional problems 37 result from a combination of treatment and diseaserelated factors. The diverse etiologies of these two symptoms can have broad and significant effects on other QOL domains. However, strategies to overcome their effects have not been well-defined and health care providers must be creative in designing interventions to improve patient outcomes. Regardless of the etiology and incidence of specific long-term physical effects, a question remains: What is the significance of long-term physical effects on normal daily functioning of the individual survivor? Descriptive data of physiological effects do not show this level of relevance. However, a few investigations have begun to study the relationship between long-term physical effects and QOL. For instance, one study found that QOL was inversely related to the number and severity of disorders experienced by the survivor. 26 Another found that patients over 30 years at the time of transplant had more severe and prolonged physiological effects and reduced QOL regardless of the passage of time after BMT. 25 Continued study of long-term physical effects is essential. Patterns of physiological effects can be expected to change as treatment and graft-versushost disease regimens change. Some effects may increase in frequency, others may decrease, and some new unanticipated effects may be recognized. For instance, before immunosuppressive treatment of cGVHD, the incidence of severe, generalized scleroderma and respiratory insufficiency occurred in 50% of transplant survivors. Now the problem is observed in only 5% to 10% of survivors. 6 Results from long-term studies have prompted changes in doses and schedules of TBI in hopes of reducing such complications as second malignancies 19 and cognitive dysfunction.35 Pre-

WHEDON AND FERRELL

46

existing physiological effects also must be determined so that they are not wrongly attributed to, or further exacerbated by, transplant regimens. One recent prospective series, described by Andrykowski and colleagues,38 found cases of preexisting neuropsychological dysfunction, most likely due to the initial therapy, that might otherwise have been attributed to the BMT. Finally, new toxicities, yet unrecognized, may be observed in long-term survivors of autologous BMT who received intensive chemotherapy regimens not typically used in allogeneic transplantation. SECOND MALIGNANCIES

Perhaps the most worrisome complication, second only to recurrence of the original disease or cancer, is development of a secondary cancer. Figure 2 summarizes the number and types of second malignancies that have been reported to the International Bone Marrow Transplant Registry and the European Bone Marrow TransplantEuropean Late Effect Study Group in long-term survivors of allogeneic BMT. In general, BMT survivors can expect a sixfold to sevenfold increased risk of developing a malignancy over nontransplanted persons. 11 These malignancies occurred up to 14 years after transplant and included

Fig 2. Second malignancies after BMT. (Date from Kolb et el. TM)

Total patients studied in IBMTR and EBMT #new i mali~na'ncies Y unspecified heme malig-total leukemia/MDS l~mphoma solid tumors-total nonmelanoma skin melanoma dysplasia / cervical v,uiya/vaginal uterine breast oropharyn~eal thyroid soft tissue sarcoma rectal brain spinal cord seminoma squamous cell

hematologic and solid tumors. Risk factors in these patients included the use of antithymocyte globulin or monoclonal antibody (anti-CD3) as treatment of GVHD and TBI.19'39 The rate of secondary malignancies in autologous BMT survivors (who do not receive these treatments) has not yet been reported. Relatively speaking, the risk of secondary malignancy after BMT appears to be no higher than that of other curative cancer therapies. 39 However, continued efforts directed at understanding the mechanism of secondary malignancy and discovering ways to reduce or prevent its occurrence are important areas of future investigation. PSYCHOLOGICAL WELL-BEING

Psychological well-being encompasses the areas of regaining normalcy, anxiety, depression, fear of recurrence, and coping with survival. 7 The first attempts to understand posttransplant QOL focused primarily on psychological effects4~ and adjustment. Wolcott and colleagues studied 17 allogeneic survivors (median 42 months post-BMT) and found that between 15% to 25% reported significant emotional distress, low self-esteem, and less than optimal life satisfaction.2~ Since then, studies have also incorporated various psycholog9732+147=10,879 116+11=127 10 74

16 58 43

13 5 4

3 1 3 3 2 1 1 1 2 1

2

BMT: QUALITY OF LIFE

ical measures, tested in other cancer patients (ie, the Profile of Mood States, Psychological Adjustment to Illness Scale) to get a better grasp on BMT survivors' psychological well-being. Only mild to moderate psychological distress has been reported in BMT survivors. Most report they were glad to "be alive" or to have a "second chance" at life especially because most have exhausted other treatment options before they had a BMT. 7'27'3~ Despite evidence of post-BMT adverse effects (losses of physical function, spouse, job), some survivors report an unexpectedly high QOL. It may be that survivors may not want to appear ungrateful to care providers or they may be so consumed with "being alive" that they may not be able to recognize or accurately describe their QOL issues. Another image that comes from patients' descriptions of the BMT experience is that of going into a cocoon of isolation and emerging transformed to a life with a renewed and revised purpose. 7'27'30 This description is reminiscent of Victor Frankl's description in Man's Search for Meaning of enduring a horrifying experience in a concentration camp. He finds meaning in his suffering and attributes his survival to searching for new meaning in his life. 4~ Similarly, the traumatic nature of the BMT experience often remains quite meaningful and vivid to the survivor. It is not surprising that some maladaptive psychological responses of cancer survivors have been described, such as post-traumatic stress reactions experienced by war veterans and other traumatized groups. 42 Uncertainty about the future can also effect psychological well-being and the nature of survivorship. Although patients may be cured, it cannot be guaranteed. Survivors may not view themselves as totally well and healthy. Specifically, in one study, some long-term BMT survivors did not view themselves as being as healthy as others their age. 24 Significantly, unlike most physiological effects, the duration of uncertainty and time required for psychological adjustment does not appear to follow a linear recovery. 23 A better understanding of the psychological trajectory of the BMT survivor awaits further study. It is of some comfort that despite the acute and long-term trauma, only a handful of survivors have later regretted their decision to have a BMT and if able, would not do it again, z2'27

47

SOCIAL WELL-BEING

Social well-being encompasses issues of intimacy, relationships, family, employment, and social reintegration. Of these, vocational and relationships/intimacy (often explored within the context of sexuality) issues have been the major focus of QOL to date. The relationship between QOL and role function or ability to return to one's former type of employment was described by Baker and colleagues. 43 Life satisfaction was positively related to retention of pre-BMT role status, especially for men. Others report that 50% to 74% of previously employed patients return to former jobs or new full-time employment. 24'25'3~ Although health reasons were sometimes responsible for patients not returning to work, perceived job and insurance discrimination also could explain this finding. In one study, these were reported as 70% and 39%, respectively.2s Collectively, these results reflect the important role of return to work and potentially a need for more active vocational retraining and rehabilitation services for some BMT survivors. Sexuality and reproductive issues were discussed earlier in relation to physical well-being. In the area of intimacy and sexuality, some difficulty was reported in resuming relationships, whereas others reported improved relationships. 26 Some relationship difficulties were attributed to sexual dysfunction.2~ ,26.28 Family in general was viewed as more valued and important in life, and patients often attributed a high degree of QOL to close relationships and support of family.7'z7'3~ Although the family has been the focus of much oncology nursing research, the sustained effects on the family resulting from high-technology treatments requiring prolonged recovery have received little attention. How well are survivors able to regain their family roles of husband, wife, father, or mother? Are they ever perceived as able to "care for their family" or always viewed as the family member to be "cared for?" What is the nature of the family's experience post-BMT and how does it affect different members' QOL? In matched-sibling allogeneic transplants, longterm effect on the donor also is an area in need of attention. The long-term impact of the transplant experience on the relationship between the donor

48

WHEDON AND FERRELL

and the recipient, and how this changes if the donor experiences long-term effects, also is an important area of inquiry. Psychological adjustment and QOL of 18 donors was explored and compared with long-term recipient survivors. 44 Donors reported little emotional distress, high self-esteem, high current life satisfaction, and little effect on the quality of their relationship with the recipient. Although the quality of the donor-recipient relationship was unaffected by time since donation, it was highly correlated with recipient health status and psychological variables. This suggests that recipient deterioration can adversely affect donor psychological status. Between 10% to 20% of donors acknowledged some negative somatic and psychological consequences of donation (eg, self-blame when the recipient had medical complications). 44 The status of the donor within the family and how that might be influenced by recipient well-being is another area that requires a better understanding. SPIRITUAL WELL-BEING

The spiritual domain is the least well delineated in QOL studies in general and certainly within the BMT population. This focus was first defined by Ferrell and colleagues as a separate area in their earlier QOL studies and then recently in their BMT/QOL model. 7 Unique responses to their qualitative survey were grouped around the themes o f " Spirituality Increased" and' 'Increased Appreciation of Life." Thirty-three responses from the 119 subjects specifically addressed issues such as global spirituality (inner strength, conviction, and life goals), religiousness (faith in God, trust, indebtedness to God), and life appreciation (overall priorities, valued relationships). Additional responses under the theme of being healthy often referred to "spiritual health." Patients identify their religious beliefs as being important coping mechanisms, yet health care providers are often not prepared to recognize or support religious beliefs during or after the transplant process. Initial data suggest that BMT has a profound effect on spiritual well-being and significantly alters the meaning of life. 7'30 Similarly, the concepts of suffering (during the acute phase of BMT) and "meaning" attributed to the transplant are less well explored. Survivors frequently express an altered life goal or altered life meaning, but its effect on the nature

of overall survival is unclear. A distinct change is often reflected in the degree of indebtedness of the survivor towards the physicians, nurses, donors, society, and health care system. This burden can be increased by the phenomenon of "survivor guilt"; that is, experiencing some remorse in being alive knowing patients who did not survive. This feeling leaves the survivors questioning the purpose or meaning of their survival over those who "didn't make it." The effects of these experiences and the expressed view of some that survival is a "miracle" are areas for future inquiry. QUALITY OF LIFE RESEARCH ISSUES IN BMT

To date, a variety of different instruments has been used to measure QOL in BMT. Single measures representing different domains, global assessments, and qualitative and quantitative methods have been used (Table 3). Debate regarding the development of disease-specific versus general measures in QOL is the subject of other reviews4s and will not be covered here. Careful attention should be paid to instrumentation when comparing results so that the quality of survivorship can be compared in a consistent manner. Continued study of the reliability and validity of the newly developed QOL instruments29 is needed. Also, their use should be extended to different BMT subtypes in future studies. Furthermore, investigating the applicability in BMT of instruments used in other populations will further extend the understanding of the concept of QOL in the BMT population. Self-report measures are considered the most valuable in QOL research. 5'7'28'30 However, a few studies have supplemented these with physicianrated Karnofsky scores and severity of illness, 25'26"28 and another study used psychiatristrated anxiety and depression. 26 However, there is a strong agreement in the literature that QOL is a subjective phenomenon and should be based on patient self-report. Longitudinal studies are needed to further define the trajectory of recovery and survivorship. Major contributions have been made in this regard by two studies described in Table 3. Andrykowski and colleagues23 noted that, although in most cases physical recovery occurred at a steady and linear rate, psychological function appeared unaffected by the passage of time. Another study examined the first year in autologous survivors28 and sup-

BMT: QUALITY OF LIFE

49 Table 3. QOL Studies in BMT

Author Wolcott et a120

Total No./ Type of Patients 26 allo

Median Age at Survey (Range)

Median Time (Months) Post-BMT (Range)

27.9 (17-51) 42 118-89)

Measures

Global Self-assessment of current health

13 leuk 13 NM

Major Outcomes/Findings Positively associated with time since BMT.

Physical well-being Health status assessment

25% reported ongoing medical problems.

Psychological well-being Profile of Mood States Simmons Self-Esteem

15%-25% reported significant emotional distress and low self-esteem; not associated with time since BMT.

Social well-being Weissman Social Adjustment Scale (SAS-SR)

Spiritual well-being Life satisfaction Hengeveld et al.2~

17 allo

28 (18-44)

34 (12-60)

Global Interview regarding information and preparation, support, coping behaviors, family reactions

16 leuk 1 NM

15%-25% reported less than optimal life satisfaction. Subjects felt ill-prepared for post-BMT emotional and sexual problems.

Physical well-being Karnofsky (observed)

50%-100% reported sexuality and fertility problems.

Psychological well-being Beck Depression Inventory Symptom Checklist 90

Social well-being Employment status

Occupational disability.

Spiritual well-being Not measured Andrykowski et a122 23 allo 18 leuk 5NM

34,4 (19-49) 26.2 (3-52)

Global Other comments: Pre-BMT expectations--34% said they were worse off postBMT than they expected pre-BMT. Compared FLIC scores with cancer patients undergoing therapy. A follow-up longitudinal assessment of the above subjects (Andrykowski et a122) demonstrated 50% unemployed for health reasons, and psychological function did not improve with passage of time.

Physical well-being Functional Living Index Cancer (FLIC)-Total Combined Function

Psychological well-being Profile of Mood States FLIC--emotional

Social well-being FLIC-social

Spiritual well-being Not measured Andrykowski et a123 (Same as (longitudinal above) assessment)

Younger age <30 at BMT associated with less fatigue, improved physical function. Younger age <30 at BMT associated with better psychological function

WHEDQN AND FERRELL

50 Table 3, QOL Studies in BMT (Cont'd)

Author

Total No./ Type of Patients

Andrykowski et a124 29 allo

MedianAge at Survey (Range)

MedianTime (Months) Post-BMT (Range)

34.4 (18-51) 51 (12-90)

Measures

Global

26 leuk 3NM (5/29 partial match)

Major Outcomes/Findings QOL about the same as renal transplant patients. Age during BMT, education, TBI were good predictors of QOL. Sex, cGVHD, prior disease did not predict QOL.

Physical weft-being Sleep, energy, appetite scale Symptom Experience Report (SER) Perceived Health Questionnaire ((PHQ) FLIC

(compared with 29 renal transplant patients)

Older age associated with poorer physiological function, 69% reported decreased energy compared with preBMT. Perceived poorer health than others their age.

Psychological well-being Profile of Mood States

Psychological Adjustment to Illness Scale (PALS)

Greater mood disturbance than other groups. More difficult to predict than physical or functional state, Greater disturbance than coronary bypass patients.

Social well-being PAlS subscales Sickness impact Profile (SIP)

Employment

Higher education levels associated with less illnessrelated dysfunction & higher QOL (higher FLIC). 38% not employed for health reasons.

Spiritual well-being Not measured Wingard et a125

135 96 allo 32 auto 7 syn 109 leuk/ lymph 26 NM

31 (18-53)

37 (6-149)

Global Not measured

Physical well-being Health Perception Scale Health Statement Karnofsky Scale (physician & patient report) Pain Scale Clinically significant illness (physician rated)

93% Karnofsky >80; 70/79 patients matched physicians on their ratings, 70% reported 0-mild pain. 33% rated to have clinically significant illness.

Psychological well-being Not measured

Social well-being Social Function Scale Employment/school attendance Job discrimination Insurance discrimination

Spiritual well-being Not measured

51% FT; 14% PT; 32% UE. 70% reported job discrimination. 39% reported trouble getting insurance.

BMT: QUAUTY OF LIFE

51 Table 3. QOL Studies in BMT (Cont'd)

Author Altmaier et a126

Total No./ Type of Patients 12

Median Age at Survey (Range)

Median Time (Months) Post-RMT (Range)

29,4 (17-41) 32.8 (25-41)

Measures

Global

Major Outcomes/Findings Compared with chemotherapy patients; study concluded that objectively, QOL in BMT was lower than chemotherapy group; however, BMT group did not report lower function.

Physical we/I-being Physical concerns/ symptoms Mobility Self-care Karnofsky Scale

60% had 1 or more episodes of pneumonia; 75% rated self "healthy." 75% able to care for self; 83% had 90 on Karnofsky Scale.

Psychological we/I-being Degree of stress Anxiety/depression-interviewer rated

Low distress.

Social well-being Relationship changes

Sexual function Employment

20% reported improved relationships. 33% reported worsened relationships (over sexual issues). 25% reported difficulties in sexual function. 58% reported FT; 16% PT; 25% UE.

Spiritual well-being Not measured Belec 199227

24 23 allo 1 auto 16 ieuk 4 lymph 4NM (5/23 partial match)

32.7 (20-50)

23 (12-38)

Global Quality of Life Index (QLI) of Ferrans and Powers Further qualitative data gathered by an 11item semistructured interview (content analysis)

91.6% had score in upper range. OOL perceptions not effected by passage of time.

Physical well-being QLI--health/fu nctioning

Number of physicial problems associated with low health subscale; 50% had fatigue and lack of energy since BMT; 75% continued to worry about health.

Psychological well-being QLI-psychological/spiritual

Social well-being QLI-socioeconomic; family

All family scores in upper end of range indicating a high positive influence of family on patient-reported QOL.

Spiritual well-being QLI-psychological/spiritual

90% responded that the BMT experience )ed to reassessment of priorities and values,

52

WHEDON AND FERRELL Table 3. QOL Studies in BMT (Cont'd)

Author Ferrell et al7,e (Qualitative)

Total No./ Typeof Patients 119 allo

MedianAge at Survey (Range)

34.7 (18-57) 48 (3-288)

60 leuk 35 lymph 24 NM Grant et a129 (Reliability and validity reported on BMT-QOL tool developed based on interviews with above patients)

MedianTime (Months) Post-BMT (Range)

BMT-QOL tool administered to above, plus 60 additional patients

Measures

Major Outcomes/Findings

Global Qualitative 6-item open-ended questionaire (City of Hope BMT-QOLS) eg, How do you think that BMT has affected your QOL? Reported responses listed under specific domains. BMT-QOL (quantitative tool)

Responses grouped by themes and reported here under domains,

Physical well-being City of Hope BMT-QOLS

Numerous side effects (eg, weight loss, visual changes, cardiac, persistent alopecia). Decreased strength and stamina. Being healthy (physical, mental, spiritual). Being independent.

BMT-QOL

Psychological well-being City of Hope BMT-QOLS BMT-QOL

Being healthy (physical, mental, spiritual). Being normal.

Social well-being City of Hope BMT-QOLS

Work and activities are limited. Being able to work, financial success. Having family/relationships.

BMT-QOL

Spiritual well-being City of Hope BMT-QOLS

Chao et al2a

58 auto 47 lymph 11 leuk

36 (19-53)

12 months Global (QOL global scale (0-10) also Physical well-being measured Kamofsky at day (BMT questionaire with items 90, 180, in each domain) 270) Weight Appetite Sleep Colds Medicines

Spirituality increased. Increased appreciation of life. Being healthy (physical, mental, spiritual). 8.9 at 1 year Median 100% (60%-100% range) Fatigue, peripheral neuropathy, balance problems noted.

Psychological well-being Body image

Social well-being Employment Sexual satisfaction

Spiritual well-being Not measured

Did not improve with time--36% dissatisfied with sexual function.

53

BMT: QUALITY OF LIFE Table 3. QOL Studies in BMT (Cont'd)

Author Haberman ~~ Haberman et a131 (Qualitative data reported)

Total No./ Type of Patients 125 111 allo 12 syn 2 auto

MedianAge at Survey (Range) 38 (26-62)

Median Time (Months) POst-RMT (Range) 121 (6-221)

Measures

Global Themes reported from the Long-Term Recovery OpenEnded Questionaire (10 items), eg, What has the experience of reestablishing your daily life and recovering from transplant been like for you? What things have been the most difficult for you to deal with since the transplant?

Physical well-being Psychological well-being

Social well-being

Spiritual well-being Bush et a132 (Quantitative measure of above subjects)

125 111 allo 12 syn 2 auto

Global EORTC QLQ-C30

Physical well-being EORTC QLQ-C30 BMT-Specific Symptom Module Ware Health Perceptions Questionaire

Psychological well-being EORTC QLQ-C30 Demands of BMT Recovery Inventory Profile of Mood States

Social well-being EORTC QLQ-C30 Demands of BMT Recovery Inventory

Spiritual well-being

Major Outc;omes/Findings Responses grouped by themes and reported here under domains.

Dealing with physical complications. Reestablishing life was difficult. Reestablishing life was easy/smooth. Achieving a new normalcy. Recovery is dynamic process of adaptation. Life is not different. Life is slower paced. Social adjustment by family, friends, peers. Returning to work/financial concerns. Dealing with relationship changes. Dealing with social changes. A new valuing of life/a changed perspective of time. (Data not available prepublication)

WHEDON AND FERRELL

54 Table 3. QOL Studies in BMT (Cont'd)

Author Schmidt et a133

Total No./ Type of Patients 162 allo

MedianAge at Survey (Range) 32 (19-50)

Median Time (Months) Post-BMT (Range) 60 (12-156)

136 leuk 4 lymph 22 NM/ other

Measures

Major Outcomes/Findings

Global City of Hope/Stanford LongTerm BMT Survivor IndexItems listed under each domain. QOL rating (1-10)

Median rating = 9.

Physical well-being Karnofsky (physician rated), weight, appetite, sleep, sex, colds, appearance, medicines, cataracts, cGVHD, diarrhea, skin, bleeding, fever, mouth sores

31% reported cGVHD. 19% reported frequent colds. 8% reported skin changes. 39% reported cataract development. 94% reported normal appetite. 98% reported normal appearance. 69% reported sexual activity similar to pre-BMT.

Psychological well-being Physical/emotional support needs

Social well-being Marital status Employment status

74% employed.

Spiritual well-being Not measured Abbreviations: allo, allogeneic; auto, autologous; EORTC, European Organization for Research on Treatment of Cancer; FT, full-time; leuk, leukemia; lymph, lymphoma; me, months; NM, nonmalignant; PT, part-time; syn, syngeneic; UE, unemployed.

ported clinicians anecdotal observations of a dramatic, steady, and linear recovery during the first year. More effort needs to be directed in this area to define timing and complete degree of recovery in all QOL domains. An interesting issue in studying QOL in BMT survivors is the comparison of these patients with other groups. To date, QOL comparisons have been made between BMT survivors and renal transplant survivors, 24 chemotherapy patients, 26 and BMT donors. 44 Andrykowski et a124 proposes that the general population, patients being treated for other life-threatening conditions lie, coronary bypass, other cancers), and solid organ lie, kidney, heart) transplant recipients may be appropriate for comparison. For instance, justification for comparing BMT and renal transplant patients' QOL was made on the basis that both groups were similar in certain respects. Specifically, both types of transplant are (1) preceeded by a period of illness (2) performed for a life-threatening condition, (3) require medical intervention with a hospitalization and rehabilitation phase, (4) are often accom-

panied by chronic physical morbidity, and (5) marked by uncertainty about long-term survival and outcomes. Although this may be true, the usefulness of information about relative QOL will only benefit those health care providers or patients familiar with renal transplant recipients. Furthermore the use of this type of information is of questionable value in health care policy decision making and may be difficult to apply for the purpose of comparing groups of patients with different conditions. 46 Valid group comparisons might be made among different types of BMT or other high-intensity treatments. A comparison of QOL outcomes between patients choosing BMT versus a known or proposed, equally beneficial treatment option lie, autologous BMT v high-dose therapy with growth factors), or among potentially equally efficacious subtypes of BMT lie, autologous v allogeneic BMT in certain malignancies) may be useful. Information about improved QOL outcomes between equally efficacious treatments could help the patient and health team with otherwise difficult de-

BMT: QUALITY OF LIFE

cisions. Unfortunately, only rarely has there been another curative alternative. High rates of treatment-related mortality of some more investigational types of BMT (partially matched/unrelated allogeneic BMT for older chronic myelogenous leukemia patients) also must be balanced with an understanding of the QOL of long-term, noncurative, supportive care. This type of information can aid patients to better weigh the equation of QOL versus an unknown QOL in these situations. Long-term QOL measurements should be considered prospectively in the design of future therapeutic trials when evaluating different pretreatments or conditioning regimens within transplant (ie, chemotherapy alone v combined radiation/ chemotherapy regimens). Nurses' concern about QOL and developing expertise in understanding and studying QOL provides multidisciplinary opportunities to collaborate, not only in the clinical care but also in research. A final note on research of BMT survivors is the unusually high rates of participation that have been observed (between 86% to 100%) in BMT QOL studies. 25,27-29 Although this is a positive effect for researchers, it may be evidence of the spiritual domain effect of "wanting to give back" and "owing a debt of gratitude" to their health care providers who offered them a chance at cure. BMT researchers should be sensitive in their approach to survivors who may sacrifice autonomy in their sense of indebtedness. SURVIVORS' RESOURCES

Ruccione described the experience of surviving childhood cancer as "(an) epidemic of survival (that) is a remarkable achievement, but also a new public health 'problem' in the sense that it places new demands on the health care system to respond to survivors' medical, social, and rehabilitation needs" (p 9). 47 This concern exists to an even greater degree with the newly growing population of adult survivors returning to their communities, after undergoing high-technology therapies like BMT, that places tremendous physical and psychological demands on their subjects. A very real issue is whether patients have access to specialized services for survivors in their local community. If a clinic does exist, how well pre-

55

pared are the local community health care services to assess, identify, and respond to the multidimentional problems of BMT survivors? Personnel in community survivor or long-term follow-up clinics must be well-informed about the survivor's unique problems to deal with the diverse, multidimensional issues of this group. The challenge to care providers may appear even greater when the "experts" regarding BMT survivors treatment and its long-term effects are many years and miles away at a tertiary referral center, seemingly inaccessible. BMT centers have an obligation to monitor longterm effects, as well as to keep communications open and develop methods to maintain continuity of care with the patient's primary health care provider. Occasionally some issues may need to be referred back to the original treatment center. Nurses and physicians in existing local community clinics must be well aware of the areas of concern of the BMT survivor, the expected course of survivorship, and available community resources to assist patients. Regular monitoring of survivors concerns can alleviate much anxiety over symptoms and feelings that worry even the healthiest survivor that the original disease has returned. Resources that need to be identified specifically include those which will deal with physiological, psychological, vocational, relationship/intimacy, fertility/adoption, and insurance and financial issues. Even in rural communities, survivor networking can occur through national newsletters (National Coalition of Cancer Survivors, BMT Newsletter)47'48"49 and computer bulletin boards (ie, the Prodigy system [Prodigy Services Company | , White Plains, NY]). Involvement in local cancer survivor-day celebrations or transplant center annual anniversary celebrations may be another valuable resource support available to patients. Nurses may be able to aid some patients who wish to form groups for mutual support or as networks to help new patients undergoing the experience. This type of mutual assistance may help survivors with a feeling of "giving back" and helping others. When health care providers become aware of newly developed resources, they should consider standardized ways to update long-term survivors who are not examined regularly. This is an important aspect of care that patients will not only find useful but may also recognize as a health care pro-

WHEDON AND FERRELL

56

riders' ongoing recognition of their experience and expression of continued caring and concern for their overall well-being. IMPLICATIONS FOR NURSES

Careful study of this large group of survivors of high-technology therapy contributes to nurses' understanding of other cancer survivors. This study must go beyond simply recording physical effects. Adaptation requires the skills and energy of the whole being to be successful. Nurses in follow-up clinics in BMT centers and nurses in local communities will need to be involved in data collection about patients' QOL for clinical and research purposes. Patients are very willing to share the wis-

dom of their experiences with health care providers who will listen. 49's~ Our obligation is to continue to hear their concerns. We must continue to assist patients to tolerate therapies, but we must be equally diligent in helping them to return to a life that is both productive and satisfying. ACKNOWLEDGMENT The authors would like to thank Mel Haberman and the other authors at Fred Hutchinson Cancer Research Center, and our colleagues at Dartmouth-Hitchcock Medical Center and the City of Hope Medical Center for sharing prepublication information about their QOL studies to complete the QOL table. We would also like to thank Beverly Cavanaugh for her secretarial assistance with the preparation of this manuscript.

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BMT: QUALITY OF LIFE

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