Quality of life Quality of life, taste, olfactory and oral function following ...

Bone Marrow Transplantation (2002) 30, 785–792  2002 Nature Publishing Group All rights reserved 0268–3369/02 $25.00 www.nature.com/bmt

Quality of life Quality of life, taste, olfactory and oral function following high-dose chemotherapy and allogeneic hematopoietic cell transplantation JB Epstein, N Phillips, J Parry, MS Epstein, T Nevill and P Stevenson-Moore Leukemia/Bone Marrow Transplantation Program of British Columbia, British Columbia Cancer Agency, Vancouver Hospital and University of British Columbia, Vancouver, BC, Canada

Summary: Multiple oral complaints develop following high-dose chemo/radiotherapy and hematopoietic cell transplantation (HCT) which can influence quality of life. The purpose of this investigation was to assess quality of life, oral function, taste and smell in a cohort of patients following HCT. A general quality of life survey (the European Organization for Research and Treatment of Cancer (EORTC)) Quality of Life (QOL) questionnaire (QLQ-C30), with an added oral symptom and function scale and assessment of taste and smell was administered to a consecutive series of patients at day 90–100 post HCT. General QOL was impacted by fatigue, affecting physical, social emotional and cognitive function. While oral function scales appeared to be little affected at day 90–100 post HCT, abnormalities of taste were reported. Reports of changes in taste and smell appeared to parallel each other and changes remained at the time of the survey post-HCT. Change in taste appeared to be closely associated with dry mouth. Patients appeared to have difficulty in differentiating sour and bitter, which had been more affected than salt and sweet taste. Females appeared to report greater changes in taste than males. Increased smell sensitivity and taste change resulted in changes in food preparation in some cases, as did reported increase in sensitivity to sour and bitter taste. Acute complications are well known to affect QOL during the early period following HCT, but little assessment of long-term changes in oral QOL and taste has been conducted following transplant. The EORTC QLQ C-30 questionnaire with the oral addendum provides a measure of the quality of life and oral function, and may provide useful outcome measures for assessment of oral care prevention and management in HCT patients. Bone Marrow Transplantation (2002) 30, 785–792. doi:10.1038/sj.bmt.1703716 Keywords: quality of life; oral function; taste; olfaction; oral complications of hematopoietic cell transplant

Correspondence: Dr JB Epstein, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC, Canada V5Z 4E6 Received 24 January 2002; accepted 29 April 2002

Quality of life (QOL) following treatment of malignant disease is an area of increasing interest. Good QOL is a state of physical, psychological and social well-being, in which the individual is able to perform everyday activities and reports satisfaction with daily function.1 QOL acute oral complications of hematopoietic cell transplant (HCT) include: painful mucositis, dry mouth, altered or reduced taste and oral infections that may lead to the need for antimicrobial medication, parenteral analgesics, tube feeding or total parenteral nutrition, all of which may negatively impact quality of life, prolong hospitalization, and increase the cost of care.2 Oral mucositis has been rated by patients as the single most debilitating complication of HCT.3 Chronic complications following HCT that may involve the oral cavity include graft-versus-host disease (GVHD), that may result in mucosal damage causing pain, dry mouth, prolonged risk of oral infection, increased risk of dental cavities, and cause limitation of oral function including mastication, swallowing and speech. Despite the continuing and considerable impact of HCT on QOL, only a limited number of studies have assessed QOL following treatment.2–13 The findings of these studies are varied and general satisfaction with life was seen in some studies following HCT,9 while negative impacts4,7,13 or mixed impact6,10,11,14 upon QOL are also reported. While overall QOL following HCT has been assessed in most of the reports to date, little is known about the quality of oral function and taste and olfaction following HCT. Even in the studies that have addressed oral complications, oral function, taste and smell have not been the focus of the investigation.15–19 The perception of flavor involves olfactory, tactile and thermal sensations as well as taste.20,21 Somatosensory stimuli, taste and smell are tightly integrated with eating and may be difficult to appreciate as separate senses. When damaged, the peripheral structures for taste can regenerate; the average life of a taste receptor is 10 days but can extend to a month or longer.21 Olfactory neurons are also capable of regeneration; however, the degree of regeneration depends upon the severity of damage.21 Patients undergoing radiation and/or chemotherapy may experience reduced taste (ageusia) or altered taste (dysgeusia), which may have a significant impact on QOL. Patients undergoing HCT may suffer significant weight loss due to decreased food intake, decreased nutrient absorption

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and increased metabolic demand. In one study, 45% of hospitalized adult patients lost 10% of their body weight and 25% lost 20% or more of their body weight.22 Causes of decreased food intake may include: lack of desire for food induced by nausea and altered taste or smell, oropharyngeal mucositis causing pain, dysphagia due to cancer or cancer treatment and/or hyposalivation, and decreased interest in food associated with depression. It may be difficult for patients to resume eating when suffering from nausea, dry mouth, reduced or altered taste and smell, and dysphagia following cancer treatment. There has been limited study of taste changes in the patient undergoing radiation therapy, chemotherapy and those receiving HCT.15–19,23 Chemotherapeutic drugs that have been associated with taste changes include: cisplatin, carboplatin, cyclophosphamide, doxorubicin, 5-fluorouracil, levamisole, and methotrexate.24 Chemotherapy which targets rapidly dividing cancer cells may also affect other rapidly dividing cells in the body (eg mucosal cells lining the gut) and since taste and olfactory receptors rapidly proliferate (every 10 and 30 days, respectively) they may also be affected.24 Taste changes following chemotherapy were assessed by questionnaire in 284 adults, were frequently reported in patients who had a dry mouth, and were often associated with nausea and vomiting.25 Chemotherapy may have an immediate effect on taste and some patients complain of a bitter taste during the administration of the drug and these changes may continue for weeks or months. For example, 77% of patients treated with cisplatin experienced a metallic taste, which lasted for a few hours to 3 weeks.24 A variety of drugs pass into saliva, which may be tasted or smelled in the oropharynx or nasal cavity or by a venous taste phenomenon where a drug diffuses from the blood to the taste receptors.26 Other sources of bad taste and smell during cancer therapy include: dental disease, poor oral hygiene, bacterial, viral or fungal infections of the oral/nasal cavity, postnasal drip, gastroesophageal reflux, volatile compounds in exhaled air and oral bleeding.26 Taste has been the subject of a limited number of transplant studies with the threshold for salt altered in these reports.15,17,23 Dietary management may include increase in the concentration of flavor ingredients to compensate for sensory loss.18 Patients undergoing chemotherapy may also report dysosmia, which may occur as a result of the drugs diffusing from the nasal capillaries to the olfactory receptors or by orthonasal olfaction.26 Some patients undergoing chemotherapy appear to have a heightened sensitivity to odors and may become nauseated when presented with certain odors. Olfactory hallucinations may also occur in individuals who are subjected to intensely emotional experiences, such as undergoing chemotherapy and they may recall a chemical odor just by thinking about the therapy.26 Radiation therapy may impact chemosensory function. Twenty-six patients receiving head and neck irradiation were assessed for taste loss and xerostomia, by questionnaire and threshold taste testing.16 Taste loss was related to the portion of the tongue in the radiated field, but no relationship between the recovery of taste and saliva function was identified.16

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Olfactory loss may result from the direct toxic effects of radiation therapy and resolution may take more than 6 months.21,26,27 During a course of radical radiation therapy for head and neck cancer, salivary function decreased after the first week and taste function was impaired by the second week of treatment.27 Considerable change in taste occurs during radiation therapy and return to pretreatment taste sensation may not occur.28–30 The etiology of taste disorders are likely multifactorial in patients receiving HCT.24 Agents such as tamoxifen that effect hormonal changes may also affect taste.21 Hyposalivation during cancer therapy, mouth breathing and sideeffects of a number of medications including antiemetics, antidepressants and antihypertensives may lead to taste changes.24 Damage to salivary glands may reduce saliva preventing tastants from entering solution.26 Shifts in the oral flora, such as overgrowth of fungi,30 may affect taste. Some reports in the literature link hypogeusia and zinc deficiency,31–34 and some drugs that cause hypogeusia possess a sulfhydryl group which may bind to zinc. Despite this, zinc supplementation studies present conflicting results.33,34 When patients say that food does not taste good, they may not be referring to sensory alteration, but may be referring to a hedonic change where food tastes as it always did but is no longer pleasant.21 Because of the limited study of taste and smell in HCT to date, and the known impacts on QOL, we assessed the quality of life, oral symptoms, taste and smell in a cohort of patients following HCT.

Materials and methods Patient characteristics The survey was completed by 50 patients treated between July 1999 and July 2000. Equal numbers of males and females with a mean age of 39.5 ⫾ 8.7 years participated. The medical diagnoses leading to transplant were: acute myelogenous leukemia (AML) in 14; myelodysplastic syndrome (MDS) in 6; chronic myelogenous leukemia (CML) in 10; acute lymphoblastic leukemia (ALL) in 6; lymphoproliferative disease in 7 (chronic lymphocytic leukemia 1; lymphoma in 6 (diffuse small cleaved cell 5; diffuse large cell 1)), multiple myeloma (MM) in 5; and severe aplastic anemia (AA) in 2 patients. All patients had received allogeneic (allo) transplantation, with related donors in 39 (2 of whom received peripheral stem cell transplants) and 11 unrelated donors. Transplant conditioning included total body irradiation in 31 patients. At the time of completing the survey (day 90–100 post-transplant), the patients median WBC (all ⫻ 103/ml) were: 4.20 ⫾ 2.87, granulocytes 2.40 ⫾ 2.53, RBC 3.25 ⫾ 0.47, Hgb 104.5 ⫾ 14.21, HCT 0.31 ⫾ 0.04 and platelets 109 ⫾ 78. Twenty-one (42%) patients were taking prednisone, at a median daily dose of 15.0 ⫾ 37.5 mg, 36 patients were taking cyclosporine at a daily does of 250 ⫾ 117 mg, and three patients tacrolimis at a daily dose of 4.0 ⫾ 1.2 mg.


Supportive care Patients were treated in a high-efficiency particulate air (HEPA)-filtered, positive pressure, Leukemia and Bone Marrow Transplantation Unit. Low bacterial content food and Hickman catheters were used routinely. Empiric intravenous antibiotics, amphotericin B, acyclovir, CMVnegative blood products, ganciclovir and total parenteral nutrition were given as required. All patients received antifungal prophylaxis with intravenous amphotericin B (10 mg/m2/day), and chlorhexidine mouth rinse (0.12%) and normal saline rinses as tolerated. Oral mucositis related discomfort was managed with oral benzydamine rinse (Tantum; 3M, Canada) and patient-controlled narcotic analgesics with morphine or hydromorphone. Questionnaire QOL was assessed in 50 consecutive patients at day 90– 100 post transplant. A previously developed questionnaire based upon the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ-C30) questionnaire with an addendum developed to assess oral symptoms and function was provided to the patients.35,36 A taste/smell addendum was added to this questionnaire. All patients completed the standard institutional approved consent form. The QLQ-C30 was assessed according to published criteria that combine responses to questions into domains of physical, emotional, cognitive and social function, global health, nausea and vomiting and pain.37 The 18 items comprising the oral symptom and function scale were grouped into four domains as previously described:35 F1 included items pertaining to face and mouth pain; F2 included items pertaining specifically to tooth pain; F3 included items pertaining to mouth function, such as chewing and swallowing without reference to pain; and F4 included items pertaining to changes following cancer therapy. Taste items were designed to detect reported changes of intensity, either increase or decrease of taste in general and specifically with respect to the taste of salt, sweet, sour and bitter. The taste and smell items were rated on a scale from 1 to 4, with 1 representing ‘Not at all’, 2 ‘A little’, 3 ‘Quite a bit’, and 4 ‘Very much’. Two items were also included to measure changes in smell intensity. The correlation structure of the taste and smell items was analyzed. Changes in symptoms were assessed using Wilcoxon signed ranks tests and Pearson correlation coefficients were calculated to compare the relations between various factors and the global and oral function scales.38

Results The results of the QLQ C30 survey with oral addendum are shown in Table 1, as analyzed by the domains of physical, emotional, cognitive and social function, global health, nausea and vomiting and pain. The distribution of responses to the taste and smell items are shown in Table 2. The 18 items comprising the oral symptom and function scale were grouped into four domains (Table 3): mouth and face pain

Table 1 Quality of life (EORTC QLQ-C30) domains at day 90–100 post-hematopoietic cell transplantation Domain QLQ-C30 Physical function Role function Emotional function Cognitive function Social function Global health status Fatigue Nausea/vomiting Pain Dyspnea Insomnia Appetite loss Constipation Diarrhea Financial difficulties

787

Mean (standard error)

60.80 40.00 77.89 77.21 55.10 50.85 48.97 21.33 19.67 20.40 24.49 29.33 6.94 13.33 36.73

(3.75) (5.35) (3.44) (3.99) (4.56) (2.57) (3.27) (3.69) (3.25) (3.87) (4.64) (4.82) (2.80) (3.01) (4.98)

(F1), dental pain (F2), oral function (including chewing, swallowing, and speech) (F3) and items pertaining to oral changes following treatment (F4). There was not a great deal of change in taste or smell reported at day 90–100 (Table 4). The most change was reported for an overall decrease in taste, although the reported decrease in taste was not significantly different from the reported increase in taste (P = 0.4). No differences in taste change were seen when assessing current use of immunosuppressive medications. The correlational structure of the components of taste and smell is presented in Table 5a and b. The relatively high correlations in the upper left corner suggests that reported increases (or not) tend to occur in all components in the same manner. Similarly the high correlations in the bottom right corner suggest that decreases in taste also tend to go together within individuals. The individual taste components were combined into two scales representing stronger and weaker taste, and the resulting scales were correlated with the general taste and smell increase and decrease items (Table 5b). Increases in taste and smell overall, as well as increases in taste components tend to go together as evidenced by the positive correlations, significant at the 0.005 level. Corresponding decreases do not show such a clear pattern, probably because of the lack of reported decreases. Mouth pain was reported to be associated with emotional function (⫺0.367, P ⬍ 0.01), and cognitive function (⫺0.358, P ⬍ 0.05). Overall change in taste and reduced taste were reported to have no significant association with function or QOL. Constant taste change either stronger (⫺0.372, P ⬍ 0.05) or weaker (⫺0.405, P ⬍ 0.05) was associated with physical function, as was stronger taste with social function (⫺0.324, P ⬍ 0.05), although no significant effect was reported on overall QOL. Changes in sour taste were reported to be associated with physical function (weaker sour taste ⫺0.308, P ⬍ 0.05; stronger sour taste ⫺0.355, P ⬍ 0.05). Increase in smell sensitivity was associated with physical function (⫺0.331, P ⬍ 0.05). Factor analysis using a varimax rotated component Bone Marrow Transplantation


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Table 2

Change in taste and olfaction reported at day 90–100 following hematopoietic cell transplantation

Variable

Severity (%)

Change in taste Taste sensitivity reduced Taste sensitivity increased Abnormal taste after meals Abnormal taste constant Sweet stronger Sweet weaker Sour stronger Sour weaker Bitter stronger Bitter weaker Change in smell Smell decreased Smell sensitivity increased Prepare food differently

None

Mild

Moderate

Severe

Missing

34 36 44 52 58 48 62 44 58 46 64 74 74 62 66

44 34 26 28 20 16 8 26 8 28 8 8 6 10 28

12 18 12 6 6 16 10 14 10 14 4 10

6 2 2 4 6 6 4 2

4 10 16 10 10 14 16 14 24 8 24 2 18 12 6

Table 3 Oral quality of life domains at day 90–100 posthematopoietic cell transplantation Domain

Mean (standard error)

Oral QOL scale Mouth/Face pain (F1) Tooth pain (F2) Oral function (F3) Post treatment oral changes (F4)

Table 4

1.17 1.50 1.53 1.05

(0.04) (0.08) (0.06) (0.03)

6 2 8

8

matrix analysis was conducted on the taste/smell addendum (Table 6), which revealed a possible three-factor solution, sorting into strong, weak and change in taste or smell and the four-factor solution split increase or decrease in taste and smell. This suggests the combination of factors that may be combined in future analyses. Change in smell was less often reported and less dramatically changed, but appeared to parallel the change in taste sensitivity. In the survey, patients appeared to have some difficulty differentiating sour and bitter, resulting in increased missing responses by patients. Sour and bitter appeared to be more changed than other tastes. Females

Report of taste/smell change post-hematopoietic cell transplantation

Taste increase Taste decrease Smell increase Smell decrease

Change in sense of taste Taste decreased Taste increase Bad after eating Bad always Salt stronger Salt weaker Sweet stronger Sweet weaker Sour stronger Sour weaker Bitter stronger Bitter weaker Change in smell Smell decreased Smell increase


4

Not at all

A little

Quite a bit

Very much

44 36 62 74

26 34 10 6

12 18 8 0

2 2 8 2

n

Min

Max

Median

Mean

Std. dev.

48 45 42 45 45 46 39 43 42 43 38 46 38 49 41 44

1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

4 4 4 4 4 4 4 4 4 4 3 4 3 4 4 4

2 2 1 1 1 1 1 1 1 1 1 2 1 1 1 1

1.90 1.84 1.67 1.58 1.56 1.65 1.38 1.77 1.48 1.70 1.37 1.74 1.21 1.47 1.15 1.57

0.857 0.824 0.816 0.812 0.893 0.875 0.782 0.996 0.890 0.832 0.714 0.880 0.528 0.915 0.527 0.998


Table 5

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Pearson correlations coefficients of taste items and change in intensity of taste and olfaction Salt stronger

Sweet stronger

Sour stronger

Bitter stronger

Salt weaker

Sweet weaker

Sour weaker

0.730** 0.772** 0.679** 0.058 0.271 0.458** 0.227

0.671** 0.595** 0.353* 0.473** 0.385* 0.188

0.791** 0.162 0.291 0.315 0.348*

0.081 0.255 0.454** 0.262

0.702** 0.329 0.520**

0.641** 0.647**

0.731**

Smell decrease

Taste increase

0.153 0.199 0.222

0.552** 0.487**

(A) Taste Sweet stronger Sour stronger Bitter stronger Salt weaker Sweet weaker Sour weaker Bitter weaker

Taste deacrease

Weaker

Stronger

(B) Change in intensity of taste/olfaction Weaker Smell decrease Taste increase Stronger Smell increase

0.335* 0.196 0.303 0.198 0.337*

0.526** 0.224 0.439** 0.178

0.426**

*Significant at the 0.05 level (two-tailed). **Significant at 0.005 level (two-tailed)

Table 6 Varimax rotated principle factor analysis of the taste and smell addendum Component Strong Change 1 Salt stronger Bitter stronger Bad always Sour stronger Bad after eating Sweet stronger Prepare food differently Bitter weaker Sweet weaker Salt weaker Smell decreased Sour weaker Smell increase Taste decreased Change in smell Change in sense of taste Taste increase

0.94 0.93 0.89 0.88 0.74 0.65 0.61

Weak Change 2

0.40 0.31 0.56 0.89 0.88 0.82 0.77 0.65

0.36 0.44 0.39 0.37

Overall Change 3

Change in smell correlated with change in taste (0.388, P ⬍ 0.01). Report of dry mouth correlated with change in taste (0.425, P ⬍ 0.01). Reduced taste sensitivity correlated with reduced sensitivity to sweet (0.702, P ⬍ 0.01), sour (0.641, P ⬍ 0.01), bitter (0.647, P ⬍ 0.01) and bitter correlated with sour taste (0.801, P ⬍ 0.01). Reported change in smell was correlated with increased smell (0.990, P ⬍ 0.01), and change in food preparation (0.513, P ⬍ 0.01). Change in food preparation correlated with stronger taste sensitivity (0.472, P ⬍ 0.01), increased sour (0.467, P ⬍ 0.01), increased bitter (0.513, P ⬍ 0.01) and change in smell (0.513, P ⬍ 0.01). Report of dry mouth was correlated with report of change in oral function (0.681, P ⬍ 0.01). Discussion

0.31 0.79 0.78 0.74 0.70 0.50

provided a greater report of taste change than males with increase in salty taste (females mean 1.96 ⫾ 0.19; males 1.32 ⫾ 0.14, P = 0.009), stronger sweet taste (females mean 2.14 ⫾ 0.21; males 1.38 ⫾ 0.19, P = 0.005), and stronger sour taste (females mean 1.93 ⫾ 0.19; males 1.43 ⫾ 0.15, P = 0.041). Correlations were seen between reported overall taste change and decreased taste sensitivity (0.654, P ⬍ 0.01), although increased taste (0.490, P ⬍ 0.01), increased bitter taste (0.444, P ⬍ 0.01) and sour (0.415, P ⬍ 0.01) was seen in some cases. Taste change was reported continuously (0.454, P ⬍ 0.01), and after eating (0.490, P ⬍ 0.01).

QOL in HCT is increasingly recognized as an important outcome of transplant.8 Despite this, few studies have assessed QOL following treatment.2–14 General satisfaction with life has been shown in studies following HCT,9 while negative impacts4,7,13 or a mixed impact6,10,11,14 upon QOL have been reported. QOL was assessed in 56 HCT patients, comparing physical, emotional and social function in the first year posttransplant (n = 15) and more than 1 year post-transplant (n = 41), using the Functional Assessment of Cancer Therapy (FACT-BMT) and the EORTC QLQ-30.4 Reduced QOL was seen in the first year post-transplant in physical and emotional well-being and associated with loss of appetite, fatigue, pain, dyspnea and nausea and vomiting. QOL was assessed in 98 3-year survivors of HCT by interview and compared to 58 healthy controls.6 It was found that HCT patients placed increased emphasis on QOL and reported fewer problems with interpersonal relationships, sleep, depression and leisure possibilities. Another study assessed Bone Marrow Transplantation


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HCT patients at baseline (n = 68), at discharge from hospital, 100 days and 1 year post-HCT (n = 45) using a number of scales and an interview questionnaire.11 Recovery in QOL occurred over time, although approximately 20% reported psychologic distress at 1 year. QOL was worse at discharge than at day 100; however, fatigue persisted even if overall QOL improved and concerns increased over time.11 Physical and psychosocial function in patients following autologous transplants was assessed in 20 patients before and in 14 survivors between 2 and 6 months and 8 to 12 months post transplant using the EORTC-QLQ-C30, and other scales.13 The most significant deficits were impaired social function, fatigue, dyspnea, financial problems, emotional distress and functional limitations which improved over follow-up.13 QOL has been shown to improve over time in 244 HCT patients followed a median of 61 months post-transplant.14 Factors associated with poor QOL were age at HCT (⬎25 years; P ⬍ 0.01), and presence of chronic GVHD (P ⬍ 0.05). One-third of patients reported poor QOL, and less favorable QOL was reported with advanced age, female gender and in patients with GVHD.14 Twelve percent reported good QOL after 5 years, but 38% reported a poor QOL, although improvement continued beyond 5 years. Females fare less well than males in sexual and psychological domains (P ⬍ 0.01).14 In another study, QOL in 28 long-term survivors of marrow transplant7 was assessed, and the following concerns were identified: psychologic and physical health, being independent, family and personal relationships, work, happiness and having support.7 Adverse memories of the transplant, dependency on others, and health concerns about the future were reported.7 Difficulties in coping were identified with regards to post-transplant symptomology, relationships, life, work and infertility. Approximately, 25% of patients reported a positive impact6,10,11,14 of the HCT on their life. The main concerns of patients following HCT were related to health status, finances, infertility and returning to a normal life. Longterm survivors (⬎2 years) of patients with AA following transplant were assessed and QOL was described as excellent or with mild impacts, and patients had returned to a fully functioning life.9 Most studies show continuing negative effects of cancer or treatment, and sexual function and psychological well-being. In our prior study in head and neck radiation patients, the 18 items comprising the oral symptom and function scale were subjected to principal components factor analysis followed by varimax rotation to identify underlying dimensions, and four reliable and non-redundant dimensions of oral function were found.28 The factors identified were mouth and face pain, dental pain, mouth function (not directly related to pain) and speech and overall oral function, based on eigenvalue and interpretability criteria and Cronbach’s alpha reliability coefficients. This questionnaire was used in a subsequent study which showed that the EORTC QLQ-C30 with oral addendum was responsive to change throughout treatment and follow-up.29 The mean global QOL scale worsened during treatment, improved after 6 months, and did not return to pretreatment levels. Mood complaints and effect upon social activity was reported by approximately half of the patients.29 Following


radiation treatment all four oral scales were affected similarly: facial and oral pain, dental pain, mouth function and changes in oral QOL. The oral scales demonstrated the greatest changes throughout treatment and the pain scales showed a greater tendency to return to pretreatment levels. Most severe oral pain was present at the end of radiation therapy, which has been correlated with severity of mucositis28 and pain did not return to pretreatment levels at 6 months.29 Similar findings were reported in our initial study where patients were assessed following head and neck radiation therapy.28 Xerostomia, dysphagia and change in taste following radiation therapy were the primary complaints of patients in both studies.28,29 In the current study of patients at day 90–100 post-HCT, the greatest changes in QOL were seen to be the impact upon physical, emotional, cognitive, and social function. Global health status, and fatigue were reported over a broad range, with an overall moderate impact and financial difficulties were also noted. Fatigue was found to have the greatest impact upon QOL in our study. Gastrointestinal symptoms had limited impact upon QOL. Therefore, the findings in this study at day 90–100 post-transplant reflect the literature where QOL is impacted in a range of areas, and influences daily living that persist at day 90–100. We found limited reported impact of oral function scales on QOL at day 90–100 post-HCT. Approximately 20% of patients reported moderate to severe change in taste at the time of the survey. More patients reported reduced intensity of taste, abnormal tastes and change in smell with increased smell sensitivity. This increase in smell sensitivity may explain the response of some inpatients to food odors. Prior studies of taste in transplant patients showed taste change, particularly related to salt threshold.15,17,23 In one study, thresholds were assessed for the four tastes using the up-down staircase method in 11 children undergoing HCT compared with 20 healthy children.17 No differences were seen on admission between HCT and control patients. Only minor changes were noted, with salt threshold increased by day 2 post-HCT.17 Interestingly, these authors note that taste changes identified did not account for reported taste change. A retrospective taste study was conducted in 15 allo-HCT patients a mean of 30.6 ⫾ 15.8 months postHCY,23 compared to eight auto-HCT patients a mean of 24.12 ⫾ 12.18 months and 20 consecutive normal subjects by threshold taste testing.23 In allo patients, hypogeusia to salt (P = 0.0002) and sour (P = 0.001), but no difference in sweet or bitter were seen. Auto recipients showed reduction in bitter threshold (NS). Late and selective differences in taste were also seen and were not necessarily related to chronic oral GVHD.23 A study by Mattsson et al15 evaluated 10 patients who experienced taste changes during the aplastic phase of HCT compared with 10 control subjects. The threshold for salt was most profoundly affected. Taste recovered by 1 year post-HCT in 80% of patients. The combinations of factors assessed in the taste/smell addendum in the current study, should be interpreted with caution as the results excluded patients with missing responses. Taste changes appeared to have recovered in large degree by day 90–100, although change in taste was variable with some patients having increased and others reduced taste sensitivity. Similar changes were noted


between various parameters of taste, with essentially consistent changes in all tastes, whether this be increased or decreased. Females appeared to have greater reported taste abnormalities following transplant than males. In a prior study we demonstrated content and face validity of the EORTC QLQ-C30 with the oral addendum.28 In a subsequent study we evaluated consecutive patients during and following radiation therapy and found that the survey tool with oral addendum was responsive to change over treatment. Furthermore, it was apparent that the oral complications observed did contribute to the overall QOL as assessed in the EORTCQLQ-C30.29 This study is the first to use the QLQ-C30 with an oral, taste and smell addendum in patients following HCT. Impacts on QOL continue at day 90–100, although taste improvements were reported over time following HCT which is consistent with recovery of taste and smell receptors,21 as reported by Matteson et al,15 and with improvement in hyposalivation that is often seen by day 90–100. This survey tool will allow for the follow-up of transplant patients so that impact on and recovery of taste may be assessed from the patient’s perspective. The EORTC oral quality of life survey with oral and taste and smell addendum provide data on oral symptoms and function following cancer therapy. Continuing research is needed to develop an understanding of the nature, frequency, severity and duration of taste and smell alterations and their significance in the quality of life of cancer patients. The literature yields little information on the impact of taste and smell abnormalities, although those active in patient care are frequently confronted with these complaints from patients. In addition to quality of life, the ability to maintain weight and to resume and maintain oral intake may have a significant impact on the outcome of therapy and QOL. Advances in non-oral feeding including tube feeding and total parenteral nutrition have enhanced the ability to treat patients through extended periods without oral intake, but do contribute to the cost of care. A more thorough understanding of taste complaints and possible interventions may impact upon the outcome of cancer therapy and improve the quality of life of these patients.

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8 9 10 11

12 13

14 15 16 17 18 19 20 21

References 22 1 Gotay CC, Moore TD. Assessing quality of life in head and neck cancer. Quality of Life Res 1992; 1: 5–17. 2 Sonis ST, Oster G, Fuchs H et al. Oral mucositis and the clinical and economic outcomes of hematopoietic stem cell transplantation. J Clin Oncol 2001; 19: 2201–2205. 3 Bellm LA, Epstein JB, Rose-Ped A et al. Patient reports of complications of bone marrow transplantation. Supp Care Cancer 2000; 8: 33–39. 4 Kopp M, Schweigkofler H, Holzner B et al. Time after bone marrow transplantation as an important variable for quality of life: results of a cross-sectional investigation using two different instruments for quality-of-life assessment. Ann Hematol 1998; 77: 27–32. 5 Neithammer D, Mayer E. Long-term survivors: an overview on late effects, sequelae and second neoplasias. Bone Marrow Transplant 1998; 21 (Suppl. 2): S61–S63. 6 Badell I, Igual L, Gomez P et al. Quality of life in young

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24 25 26 27 28

adults having received a BMT during childhood: a GETMON study. Bone Marrow Transplant 1998; 21 (Suppl. 2): S68– S71. Molassiotis A, Morris PJ. The meaning of quality of life and the effects of unrelated donor bone marrow transplants for chronic myeloid leukemia in adult long-term survivors. Cancer Nurs 1998; 21: 205–211. Wingard JR. Quality of life following bone marrow transplantation. Curr Opin Oncol 1998; 10: 108–111. Deeg HJ, Leisenring W, Storb R et al. Long-term outcome after marrow transplantation for severe aplastic anemia. Blood 1998; 91: 3637–3645. Gotay CC, Muraoka MY. Quality of life in long-term survivors of adult-onset cancers. J Natl Cancer Inst 1998; 90: 656–667. McQuellon RP, Russell GB, Rambo TD et al. Quality of life and psychological distress of bone marrow transplant recipients: the ‘time trajectory’ to recovery over the first year. Bone Marrow Transplant 1998; 21: 477–486. Molassiotis A. A conceptual model of adaptation to illness and quality of life for cancer patients treated with bone marrow transplants. J Adv Nurs 1997; 26: 572–579. Wettergren L, Languis A, Bjorkholm M, Bjorvell H. Physical and psychosocial functioning in patients undergoing autologous bone marrow transplantation – a prospective study. Bone Marrow Transplant 1997; 20: 497–502. Chiodi S, Spinelli S, Ravera G et al. Quality of life in 244 recipients of allogeneic bone marrow transplantation. Br J Haematol 2000; 110: 614–619. Mattsson T, Arvidson K, Heimdahl A et al. Alterations in taste acuity associated with allogeneic bone marrow transplantation. J Oral Pathol Med 1992; 21: 33–37. Fernando IN, Patel T, Billingham L et al. The effect of head and neck irradiation on taste dysfunction: A prospective study. Clin Onc 1995; 7: 173–178. Barale K, Aker SN, Martinsen CS. Primary taste thresholds in children with leukemia undergoing marrow transplantation. J Parent Ent Nutr 1982; 6: 287–290. Bartoshuk LM. Chemosensory alterations and cancer therapies. NCI Monogr 1990; 9: 179–184. Bernstein IL. Learned taste aversions in children receiving chemotherapy. Science 1978; 200: 1302–1303. Seiden A (ed.). The initial assessment of patients with taste and smell disorders. In: Taste and Smell Disorders. Thieme: New York, 1997, pp 4–19. Duffy V, Lucchina L, Fast K, Bartoshuk L. Taste and cancer. In: Berger A et al (eds). Principals and Practice of Supportive Oncology. Lippincott-Raven Publishers: Philadelphia, 1998, pp 141–151. Holmes S. Food avoidance in patients undergoing cancer chemotherapy. Supp Care Cancer 1993; 1: 326–330. Marinone MG, Rizzoni D, Ferremi P et al. Late taste disorders in bone marrow transplantation: clinical evaluation with taste solutions in autologous and allogeneic bone marrow recipients. Haematologica 1991; 76: 519–522. Wickham RS, Rehwaldt M, Kefer C et al. Taste Changes Experienced by Patients Receiving Chemotherapy. ONF 1999; 26: 697–706. Wickham RS, Rehwaldt M, Kefer C et al. Taste changes experienced by patients receiving chemotherapy. ONF 1999; 26: 697–705. Bartoshuk L. Chemosensory alterations and cancer therapies. NCI Monogr 1990; 9: 179–184. Mossman K, Shatzman A, Chencharick J. Long-term effects of radiotherapy on taste and salivary function in man. Int J Radiat Oncol Biol Phys 1982; 8: 991–997. Epstein JB, Emerton S, Kolbinson D et al. Quality of life and

791



792

29 30 31 32

33

oral function following radiotherapy for head and neck cancer. Head Neck 1999; 21: 1–11. Epstein JB, Robertson M, Emerton S et al. Quality of life and oral function in patients treated with radiation therapy for head and neck cancer. Head Neck 2001; 23: 389–398. Fernando I, Patel T, Billingham L et al. The effect of head and neck irradiation on taste dysfunction: a prospective study. Clin Oncol 1995; 7: 173–178. Abu-Hamdan D, Desai H, Sondheimer J et al. Taste acuity and zinc metabolism in captopril-treated hypertensive male patients. Am J Hypertens 1988; 1: 303S–308S. Ruz S, Cavan K, Bettger W et al. Development of a dietary model for the study of mild zinc deficiency in humans and evaluation of biochemical and functional indices of zinc status. J Clin Nutr 1991; 53: 1295–1303. Lindsey A, Piper B. Anorexia, serum zinc, and immunologic response in small cell lung cancer patients receiving chemotherapy and prophylactic cranial radiotherapy. Nutr Cancer 1986; 8: 231–238.


34 Ripamonti C, Zecca E, Brunelli C et al. A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. Cancer 1998; 82: 1938–1945. 35 Aaronson NK, Ahmedzai S, Bergman B et al, for the European Organization for Research and Treatment of Cancer, Study Group on Quality of Life. The EORTC QLQ-30: a quality of life instrument for the use in international trials in oncology. J Natl Cancer Inst 1993; 85: 365–376. 36 Fisher LD, Van Belle G. Biostatistics: A Methodology for the Health Sciences. John Wiley: New York, 1993, pp 631–647. 37 Sonis ST, Eilers JP, Epstein JB et al. Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy. Cancer 1999; 85: 2103–2113. 38 Epstein JB, Stewart KH. Radiation therapy and pain in patients with head and neck cancer. Oral Oncol, Eur J Cancer 1993; 29B: 191–199.