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3datos.esBone Marrow Transplantation (2004) 34, 729–738& 2004 Nature Publishing Group All rights reserved 0268-3369/04 $30.00 Quality of life assessment in patients undergoing reduced intensityconditioning allogeneic as compared to autologous transplantation: resultsof a prospective study M Dı´ez-Campelo1, JA Pe´rez-Simo´n1, JR Gonza´lez-Porras1, JM Garcı´a-Cecilia2, M Salinero1,MD Caballero1, MC Can˜izo1, EM Ocio1 andJF San Miguel1 1Servicio de Hematologı´a, Hospital Universitario de Salamanca, Paseo de San Vicente, s/n, Salamanca, Spain; and 2Statistic’sDepartment, Faculty of Psychology, Segovia, Spain Patients’ preferences are increasingly being considered in The aim was to analyze quality-of-life (QOL) during the decision-making regarding treatment options, so that ﬁrst year post transplant in 47 patients undergoing currently, no option shouldbe pressedon patients without reduced-intensity conditioning (RIC) allotransplantation, providing information about the potential beneﬁts and and to compare these with a similar subgroup of patients harm.1,2 While choosing the best treatment option basedon receiving autologous stem cell transplantation (ASCT).
adequate evidence is possible for different diseases,3,4 risk We used self-reported questionnaires. Each answer scored groups of patients5 or disease status,6 evidence regarding from 0 (not at all) to 4 (very much), with higher scores outcome cannot always be offered.2 In particular, con- indicating worse functioning. Mean value of physical siderations concerning outcome must take into account categories among RIC transplants ranged between 1.23 more than just patient survival. Moreover, even when there and 0.77 indicating that patients scored very low for is sufﬁcient evidence in terms of survival, issues regarding physical symptoms. Patients undergoing ASCT had the long-term side-effects of intensive therapies are of higher scores in questionnaires performed early after tremendous importance for patients and their relatives,7 transplant and then gradually improved (Po0.001).
especially when treatment options include aggressive Overall, when we compared physical functioning scores, therapeutic approaches. Unfortunately, although several allo-RIC did signiﬁcantly better (P ¼ 0.049). Neverthe- studies have evaluated quality of life (QOL) of SCT less, while allo-RIC scores were signiﬁcantly better for the recipients in recent years, information remains inconclu- ﬁrst three questionnaires, ASCT patients did better in the sive. In this sense, while some authors have reportedgood last two questionnaires. These ﬁndings are in accordance physical andfunctional recovery after SCT,8,7,9–11 other with the toxicities observed in both subgroups which are studies have described important functional impairments lower in the RIC group early after transplant. No such as fatigue, psychological distress and sexual dysfunc- signiﬁcant differences were observed between either tion.12,13 In addition, most of these studies are cross- subgroup for any of the functional, social/ family, sectional, and other, longitudinal studies analyzing post psychological distress and satisfaction with doctor/nurse transplant QOL over time are required.14 Finally, previous relationship items. We have observed similar QOL among cross-sectional studies have shown that QOL might be patients undergoing RIC-allo as compared to ASCT impairedafter allogeneic transplantation more signiﬁcantly although GVHD remains an important ‘event’ in QOL.
than in autologous especially in the case of severe chronic Bone Marrow Transplantation (2004) 34, 729–738.
graft versus host disease,14–18 although as yet, there have been no longitudinal studies comparing QOL after auto- logous andallogeneic transplantation.
quality of life; QOL; reduced intensity con- In an effort to reduce the morbidity and mortality ditioning; nonmyeloablative; allogeneic transplant associatedwith allogeneic transplantation, several groupshave recently developed nonmyeloblative or reducedintensity conditioning regimens (RIC) designed to beimmunosuppressive rather than myeloablative in order toreduce the toxicity associated with high-dose chemother-apy, while maintaining the therapeutic effect of theprocedure through a graft versus leukemia reaction.19,20 Correspondence: Dr M Dı´ez-Campelo, Servicio de Hematologı´a, These RIC transplants have extended the use of allogeneic Hospital Universitario de Salamanca, Paseo de San Vicente, s/n, 37007 transplantation to patients with a high risk of transplant- Salamanca, Spain; E-mail: [email protected] relatedmortality (TRM) due to age or other concurrent Received2 March 2004; accepted2 June 2004Publishedonline 6 September 2004 In the present study, for the ﬁrst time, QOL was analyzed during the ﬁrst year post transplant in patients undergoing RIC allogeneic transplantation, andwe comparedthis cohort of patients with a similar group of patients receiving autologous SCT (ASCT) in the same institution during thesame periodof time. By d patients with a suitable donor undergo RIC only in the event of advanced age or concurrent medical condition which increases the risk of morbidity and/or mortality after conventional myeloablative conditioning (CMC) regimen.
For this reason, we did not compare RIC vs CMC since pretransplant characteristics of both subgroups of patients are signiﬁcantly different, thus hampering any conclusion regarding comparison of QOL after transplantation. For this reason, we chose to compare RIC patients with a similar group of patients without a suitable donor under- going ASCT. Moreover, ASCT is considered a procedure associatedwith a low morbidity andmortality thus making this subset of patients an interesting group to compare with RIC in terms of QOL. For this purpose, we usedself-reportedquestionnaires21 that patients completedatdifferent time-points after transplant. Questionnaires meet nancies.20 GVHD prophylaxis consistedof cyclosporine A requirements of validity, sensitivity and reliability for (CsA) plus short-course methotrexate (MTX). Acute and assessment of various issues such as physical, functional, chronic GVHD were graded by established criteria.26 In addition, 70 out of 95 patients receiving autologous stem cell transplant (ASCT) during the same period whogave their consent to enter the study were included. Onlypatients to be monitoredat our institution after the procedure were invited to enter the QOL study. Patientcharacteristics are shown in Table 1. In all, 37 patients receivedBEAM27 as the conditioning regimen. Other regi-mens usedwere: busulfan plus melphalan (eight patients), Between January 1999 andJanuary 2003, 47 out of 60 cyclophosfamide plus carboplatin plus thiotepa (six patients), patients at our institution undergoing an RIC peripheral melphalan (11 patients), busulfan plus cyclophosfamide bloodstem cell (PBSC) transplant (allo-RIC) from an HLA (seven patients) andCy plus TBI (one patient).28,29 identical sibling, gave their consent to participate in this Patients receiving RIC andASCT receiveda mean of 2 vs study. Patients gave written informed consent for inclusion 3 lines of chemotherapy prior to transplantation. While no in the protocol, which was approvedby all local ethical signiﬁcant differences were observed between the two review boards and the Spanish Drug Agency (protocol 99- groups in terms of median age, patients undergoing allo- 0151). Eligibility criteria for entry into this RIC included RIC hada more advanceddisease status as comparedto patients with a myeloidor lymphoidmalignancy potentially those undergoing ASCT (21 vs 4% high-risk patients, treatable with an allogeneic transplant, who were 45 years respectively; Po0.001). In addition, signiﬁcant differences oldor more and/or who were at high risk of transplant- were observedin terms of diagnosis (P ¼ 0.002, Table 1).
relatedmortality (TRM) according to their pretransplantevaluation.24–27 Patient characteristics are shown in Table 1.
Disease phase at transplant was categorizedas early, lowrisk (acute leukemia or poor-risk myelodysplasia in ﬁrst Informedconsent was requiredfor the prospective QOL complete remission, ﬁrst chronic–phase CML, lymphoid study. All eligible patients received the questionnaires on malignancy in ﬁrst remission), intermediate (acute leukemia days þ 7, þ 14, þ 21, þ 90, þ 180, þ 270 and þ 360 post or myelodysplasia in second or more complete remission, transplant. Questionnaires included 55 items divided into six domains assessing physical and functional environment, malignancy in secondor more remission, untreated social/family well-being andpsychological d standard-risk myelodysplasia) and advanced, high risk satisfaction with the doctor/patient and nursery/patient (refractory or relapsedacute leukemia or myelodysplasia, relationship. Each answer was evaluatedfrom 0 (not at all) blastic-phase CML, refractory or relapsedlymphoid to 4 (very much) with higher scores indicating worst malignancy andall secondtransplants). Donors were sex- functioning except for the items relatedto functional well- matchedin 51% cases andmismatchedin 49%.
being andrelationships (social andfamily well-being and Two RIC regimens basedon ﬂudarabine 150 mg/m2 plus patient/nurse or patient/doctor relationship) where higher melphalan 140 mg/m2 or ﬂudarabine 150 mg/m2 plus scores indicate a better functioning. The questionnaire was busulfan 10 mg/m2 were used, the former regimen recom- basedon FACT-BMT (version 3),22–25 including additional mended for lymphoid and the latter for myeloid malig- items regarding graft-versus-host-disease symptoms.
QOL in RIC allogeneic transplantationM Dı´ez-Campelo et al In order to perform a longitudinal assessment of QOL during the ﬁrst year after transplant, patients received the questionnaires at seven time points, as previously speciﬁed.
For cross-sectional comparisons between values obtained at the different time points, univariate ANOVA tests were performed. For longitudinal comparisons, an intrasubject model (time) was deﬁned in order to guarantee equivalence between groups, thereby conﬁguring a mixedfactorial or split-plot model30,31 in which the variability attributedtoindividual characteristics was eliminated by the maximum blocking design.32 As a statistical model for the General Model Line, a two-way, Measurement Repeated MultipleAnalysis (MR-MANOVA two way) was performedto compare the differences between both subgroups in terms of mean values considering the whole period analyzed, since the theoretical conditions (independence, normality, homoscedasticity, covariant equality and sphericity) were met andbecause the possible signiﬁcance of the intrasubjectfactor (time) was sought in combination with the different All factors which signiﬁcantly inﬂuencedQOL on univariate analysis were included in a multivariate analysis.
comparedto patients receiving allo-RIC (Table 2). No Since the variables ‘type of transplant’ and‘graft versus other severe toxicities were observedin either of the two host disease’ are mutually exclusive (where ‘type of transplant’ ¼ ‘autologous’, GVHD does not apply), a With a median follow-up of 281 days (range: 21–2196 multivariate analysis was performedinclud days) 17 patients have died and 17 have relapsed. Projected transplant,’ but excluding GVHD and then a second event-free survival (EFS) at 3 years is 51% for patients multivariate analysis was performedwhich includ undergoing RIC allogeneic transplant and 54% for those GVHD but not the type of transplant.
receiving autologous transplantation andrelapse rates did As far as the validation of the questionnaire was not signiﬁcantly differ between either subgroup (21 vs 13%, concerned, items other than those already included in ptns). Among allo-RIC patients acute graft versus host FACT-BMT, were selectedandsubjectedto the Internal disease (aGVHD) appeared at a median of 35 days (range: Validity of the Construct once the conditions necessary for the use of a Factorial Analysis were in place (sphericity test: (11% grades III–IV). Chronic GVHD ﬂared at a median of P ¼ 0.000 andKMO ¼ 710). After conﬁrming that the 168 days (104–420) with overall cumulative incidence of factors did not correlate between each other the Principal 66%. All patients included in this study who developed Components extraction methodwith Equamax rotation. In the last solution after rotation, three groups of variableswere foundwhich includ superior to 0.515, which wouldaccount for the 61.483% total variability observedin the questionnaire. This ledus to conclude that the Structural Validity of the scale had tioning categories, 13 items were analyzed. Mean values of physical categories among RIC allogeneic transplantsrangedbetween 1.23 and0.77, which indicates that, overall,patients scoredvery low for physical symptoms. Asobservedin Figure 1, mean values d change during the year post transplant (P ¼ 0.34) in thissubset of patients since scores were low even on the questionnaires performedvery early after transplant in Although the number of CD34 þ cells infusedd contrast to patients undergoing ASCT who had higher signiﬁcantly differ between either subgroup (2.3278.95 and scores on questionnaires performedon days þ 7 to þ 28 4.3872.41 s.d. Â 106 CD34 þ cells/kg for ASCT andallo- RIC, respectively; P ¼ 0.53), granulocyte engraftment was subsequent controls (scores ranging from 1.63 to 0.51, signiﬁcantly faster among patients receiving autologous Po0.001). Overall, when we comparedmean physical transplantation (Table 2). Both subgroups also differed functioning scores during the ﬁrst year after transplant regarding fever episodes (100 and 64% of patients receiving between allo-RIC andASCT patients, the former group did ASCT andRIC allogeneic transplant developedany fever signiﬁcantly better (Figure 1n, P ¼ 0.049). Nevertheless, it episode, Po0.001) andﬁnally, patients receiving ASCT shouldbe notedthat while allo-RIC scores were better for hadsigniﬁcantly more mucositis andnausea/vomiting as the ﬁrst three controls performedearly after transplant, Scores of physical well-being categories along the ﬁrst year post transplant. (a) Lack of energy (V1); (b) shortness of breath (V2); (c) needof rest (V3); (d) nausea (V4); (e) uncompliance of family duties due to physical limitations (V5); (f) pain (V6); (g) pain interferes in daily activities (V7); (h) anysymptom relatedto therapy (V8); (i) I feel sick (V9); (j) I needto stay in the bed(V10); (k) itching (V11); (l) any ocular disturbances (V12); (m) anydisturbances in mouth (V13); (n) evolution of the mean score of all categories. Days after transplant: (1) d ay þ 7 after infusion; (2) d ay þ 14; (3) d ay þ 28;(4) day þ 90; (5) day þ 180; (6) day þ 270; (7) day þ 365.
patients undergoing autologous transplant did better in the receiving RIC allogeneic transplant (Figure 1k, l, m).
þ 365, so that both curves crossedaroundd Finally, on day þ 365, 9.5% of patients receiving allo- which coincides with the median day of cGVHD ﬂare.
RIC, as comparedto 5.5% among ASCT patients More speciﬁcally, in the early post transplant period, (P ¼ 0.54), scored ‘quite a bit or very much’ to the item ‘I patients undergoing ASCT had worse scores regarding have shortness of breath,’ while 32.3% of allo-RIC vs lack of energy, needfor rest, nausea, pain or symptoms 59.1% of ASCT patients (P ¼ 0.01) scored ‘quite a bit or relatedto therapy as speciﬁedin Figure 1a, c, d, f, g andh.
very much’ to the item ‘I need to rest’.
This is in accordance with post transplant toxicities Other variables with signiﬁcant inﬂuence on mean physical well-being are summarizedin Table 3. Fever, cantly later questionnaires for ASCT patients, overall, mucositis andnausea/vomiting inﬂuencedphysical well- signiﬁcant differences persisted in favor of allo-RIC being on days þ 7, þ 14 or þ 28, while none of them had patients in the longitudinal comparison during the ﬁrst an impact after that time-point in cross-sectional analysis.
year post transplant regarding lack of energy, need of rest Nevertheless, mucositis andnausea/vomiting didinﬂuence andnausea. By contrast, upon analyzing variables related the overall physical well-being during the ﬁrst year post to GVHD symptoms such as itching, ocular or mouth transplant as assessedby longitudinal analysis (Table 3 and disturbances, we observed that, except for an initial beneﬁt Figure 2a, b). In addition, as shown in Figure 2c and d, aGVHD adversely affects QOL in the cross-sectional QOL in RIC allogeneic transplantationM Dı´ez-Campelo et al Variables with signiﬁcant inﬂuence on physical well-being during the ﬁrst year post transplant P long refers to differences between auto and RIC along the year post transplant. P-value in each time-point refers to differences observed between meanvalues in that speciﬁc day post transplant.
aP ¼ 0.032 when we comparedresults from day X+90.
Boldtype indicates statistically signiﬁcant values (lower than 0.05).
Mean physical well-being along the ﬁrst year post transplant according to the development of mucositis grades 1,2 (a); nausea/vomiting grades 1,2 (b); acute graft versus host disease (c) andchronic graft versus host disease (d). Days after transplant: (1) day þ 7 after transplant; (2) day þ 14; (3) day þ 28; (4) day þ 90; (5) day þ 180; (6) day þ 270; (7) day þ 365.
analysis performedon the ﬁrst four controls after transplant, while cGVHD hadan unfavorable impact on cluded for evaluating functional well-being (see Appendix QOL from day þ 180 and onwards. In the longitudinal A). No signiﬁcant differences were observed between either analysis, GVHD signiﬁcantly inﬂuencedQOL during the subgroup for any of the functional well-being items. Mean value of functional categories rangedbetween 2.03 and2.52 All variables which signiﬁcantly affectedphysical func- among allo-RIC patients during the ﬁrst year post tioning on univariate longitudinal analysis were included in transplant andbetween 2.04 and2.75 among ASCT a multivariate analysis andmucositis plus type of patients, so that in both groups mean scores slowly transplant were the only variables which hada signiﬁcant improvedover the year post transplant. Nevertheless, impact on physical well-being in the longitudinal analysis 14.3% of allo-RIC and26.3% of ASCT patients still had (P ¼ 0.0003 for both). By contrast, when we excluded type problems sleeping in the control performedon day þ 365 (P ¼ 0.29), while 38 vs 57.9% of allo-RIC andASCT variable which retainedstatistical signiﬁcance in multi- patients scored ‘quite a bit or very much’ to the item ‘I’m Variables with signiﬁcant inﬂuence on mean functional well-being during the ﬁrst year post transplant aP ¼ 0.036 upon comparing QOL from day o/ ¼ +90.
bP ¼ 0.02 when we comparedresults up to day +90.
Boldtype indicates statistically signiﬁcant values (lower than 0.05).
Regarding variables which could inﬂuence mean func- were scored3 or higher andno differences were observed tional well-being, only GVHD, both acute andchronic, had between ASCT or allo-RIC patients. Scores did not an adverse impact on functional well-being during the ﬁrst signiﬁcantly change during the year post transplant.
Social/family well-being and psychological distress categor- In total, 14 items divided into two domains were used to assess social/family well-being andpsychological d Although allogeneic transplantation is the best treatment tress. Within the former domain, high scores (ie, better modality for patients diagnosed with poor prognostic acute well-being for social andfamily items) were obtainedfor all leukemias or advanced stage hematological malignan- questions (see Appendix A) even in the ﬁrst controls cies,1,3,4 its efﬁcacy has been hamperedby signiﬁcant performedearly after transplantation, with mean scores ranging from 2.7 and2.7 for ASCT andfrom 2.58 to 2.64 (TRM).33 Even with the chance of being cured, some for allo-RIC in day þ 7 on d ay þ 365, respectively questions remain crucial for these patients: Does the time (P ¼ 0.29). In addition, no signiﬁcant changes in mean gainedhave sufﬁcient quality? Is curative therapy with a high mortality or persistent morbidity worth it? The answer following transplant. By contrast, sexual well-being had to these questions shouldcontribute to providing patients low scores, ranging from 0.5 in the ﬁst questionnaire to 2.2 with better information regarding quality of life which in the questionnaire performedon day þ 365 (P ¼ 0.001).
wouldbe of great use for patients andtheir physicians in In fact, this was the only item which signiﬁcantly improved standardizing practice regarding the decision-making pro- during the ﬁrst year post transplant. Finally, no signiﬁcant cess. Moreover, this information shouldbe available to the differences were observed between ASCT and allo-RIC for patients andtheir relatives in order for them to choose the most appropriate treatment option.2 With this goal in Regarding psychological distress, seven items addressing mind, in 1999, we developed a questionnaire based on symptoms of depression (see Appendix A) were evaluated.
FACT-BMT,22–25 including additional items regarding No signiﬁcant differences were observed between patients graft-versus-host-disease symptoms. The questionnaire undergoing ASCT or allo-RIC either in terms of depression was validated as previously described. We designed a or anxiety. Scores were low for depression and they did not prospective longitudinal study in order to evaluate the signiﬁcantly alter over the year post transplant. In this QOL among patients undergoing reduced intensity con- sense, 0–13% of allo-RIC and4.3–23% of ASCT patients ditioning allogeneic transplantation and compared these answered‘quite a bit or very much’ to items relatedto results to those obtainedamong patients receiving ASCT.
depression in the ﬁrst questionnaire (day þ 7) as compared RIC transplants have been developed to be immunosup- to 5–5.6% of allo-RIC and9–13.6% of ASCT patients in pressive rather than myeloablative,19,20 in an effort to reduce the high mortality rate reported after conventional Concerning symptoms of anxiety, again scores did not allogeneic transplantation in patients of advanced age or signiﬁcantly alter during the year post transplant. Never- with comorbidpretransplantation conditions.34 Moreover, theless, mean scores were slightly higher than those in addition to a lower TRM, in standard clinical practice it observedfor depression with 22.6–45.2% of allo-RIC and has been observedthat there is a signiﬁcant improvement in 19–34.4% of ASCT patients who answered‘quite a bit or QOL after RIC allogeneic transplantation although no very much’ to items relatedto anxiety in the ﬁrst study has been reported to date far evaluating the impact of questionnaire (day þ 7) as comparedto 26.3–44.4% of this procedure on QOL of these patients. On the other allo-RIC and9.1–42.9% of ASCT patients in the ques- hand, according to previous studies, age may adversely tionnaire performedon day þ 365 (P40.14).
affect QOL after transplant and, since most candidatesreceiving RIC allogeneic transplantation are of advanced Doctor/patient and nurse/patient relationship.
age or have a concurrent medical condition, QOL assess- relationship with doctors and nurses is concerned, all items ment couldbe impaired.35 In addition, since this procedure QOL in RIC allogeneic transplantationM Dı´ez-Campelo et al may reduce TRM in patients with a poor performance post transplant periodandsymptoms relatedto chronic status, a higher subset of these patients may survive after graft versus host disease adversely affected QOL after day transplant thus adversely affecting overall QOL.
þ 180, which was approximately the median day of Although it wouldbe reasonable to argue that the cGVHD ﬂare. In fact, items addressing cGVHD symptoms optimal comparison in terms of QOL wouldhave been to such as itching, ocular or mouth disturbances are variables compare patients undergoing RIC vs conventional myelo- which signiﬁcantly contributedto the poorer QOL ob- ablative conditioning (CMC) allogeneic transplantation, in servedamong allo-RIC patients after day þ 180, andthus our institution, patients with a suitable donor undergo RIC effectedthe cross between the curves of ASCT andallo- only in the event of advanced age or a comorbid medical RIC patients at that speciﬁc time-point. Although not condition which increases the risk of morbidity and/or surprising, this is an important ﬁnding since the therapeutic mortality after conventional transplantation. For this effect of allo-RIC transplantation relies mainly on the graft reason, by deﬁnition pretransplant characteristics of both versus tumor effect and, in this sense, several studies have subgroups of patients are signiﬁcantly different. An shown that cGVHD favorably affects event-free survival.37 alternative was to compare RIC patients with a similar According to this and other studies,11 cGVHD shouldalso group of patients without a suitable donor undergoing be considered an ‘event’ regarding QOL of patients, so that ASCT in the same periodof time. As a matter of fact, in the future, more speciﬁc targets for the immune response although some characteristics at transplant differ between must be exploredin order to exploit the graft versus tumor the two subgroups, none of these variables representeda contraindication to receiving one or the other option and, Quality of life scores were goodfor most of the items furthermore, none of them signiﬁcantly affectedQOL on analyzed; the same scores were found for ASCT and RIC univariate analysis. In addition, this comparison would patients regarding fuctional environment, social and family allow us to address the impact on QOL of the immune well-being, psychological distress and satisfaction with reactions inherent to the allogeneic transplant with low doctor/nurse relationships. Nevertheless, this information toxicity relatedto the chemotherapy in the RIC setting vs shouldbe interpretedwith caution since, as has been the side effects of the high doses of chemotherapy used in pointedout,12,38 patients who have suffereda stressful the autologous setting. Finally, ASCT is considered a event, such as cancer diagnosis, are grateful for treatment, procedure, which induces a low morbidity and mortality which wouldbe reﬂectedin their QOL scores. This couldbe thus making this subset of patients an interesting group to a confusing variable in studies which have compared symptoms of patients receiving bone marrow transplanta- To the best our knowledge, the present study is the ﬁrst tion with those of healthy controls.39 By contrast, it would of its kindto focus on QOL assessment after RIC not affect either the comparison between ASCT andallo- allogeneic transplantation. Moreover, so far, there have RIC patients or the tendency or evolution of symptoms in been no longitudinal studies comparing QOL after auto- patients during the year following transplant. In addition, it logous or allogeneic transplant especially during the ﬁrst shouldbe notedthat, as suggestedin previous studies, QOL year after transplant,12,36 although cross-sectional studies among patients receiving a SCT is especially hampered have shown impairedQOL among patients receiving during the ﬁrst year post transplant, with improvements allogeneic as comparedto those receiving autologous observedduring the long-term follow-up for most patients transplants mostly due to graft versus host disease-related at 2 and5 years after transplantation.7,15 Interestingly, in symptoms.14–18 In the present study, both subgroups of our study, focusing on QOL during the ﬁrst year post patients receiving either autologous or RIC allogeneic transplant, most patients gave low scores for fatigue or transplants had a similar median age although, as expected, weakness, which are some of the most common symptoms diagnosis and disease status at transplant signiﬁcantly described among SCT survivors.12,40 More speciﬁcally differed between subgroups. Interestingly, when we com- 9.5% of patients receiving allo-RIC scored ‘quite a bit or paredphysical well-being items, those patients receiving an very much’ to the item ‘I have shortness of breath’ on day RIC allogeneic transplant hada signiﬁcantly better QOL þ 365 which is in contrast to previous studies describing during the ﬁrst year post transplant, thus showing the 72% of patients who reporteddistressing levels of fatigue at favorable impact of RIC transplant on morbidity. Never- 20 months post transplant.41 Although in the current study theless, it shouldbe notedthat, in the current study, among a signiﬁcant proportion of patients (32.3% of allo-RIC) seven questionnaires, four were completedbefore d scored ‘quite a bit or very much’ to the item ‘I need to rest’ these results again compare favorably to previous studies showing that 30% of patients maintainedproblems with months after transplant may have increasedtheir weight in their energy level at 45 months post transplant.40 Other the overall comparison even though scores were better symptoms commonly described after SCT are problems among patients receiving ASCT in the questionnaires concerning sleep quality andpsychological distress.12,40 In performed after that date. Not unexpectedly, items this sense, Whedon et al42 have reportedmod concerning high-dose chemotherapy-related toxicity such severe psychological distress in 93% of patients, while other as nausea andvomiting, lack of energy or needto rest had authors have described symptoms of depression in 33–45% signiﬁcantly better scores in the allo-RIC group than in the andanxiety in 48% of patients undergoing SCT.43,44 In the ASCT group. By contrast, symptoms relatedto acute graft current study, 0–13% of patients undergoing RIC allo- versus host disease signiﬁcantly hampered QOL among geneic transplantation showedsymptoms of d patients receiving RIC allogeneic transplants in the early during the ﬁrst year post transplant, which did not signiﬁcantly differ from those patients undergoing auto- 8 Chao NJ, Tierney K, Bloom JR et al. Dynamic assessment of logous transplantation. By contrast, a higher percentage quality of life after autologous bone marrow transplantation.
of patients hadsymptoms of anxiety, ranging from 22.6 to 45.2% among patients receiving allo-RIC andthis 9 HjermstadMJ, Evensen SA, Kvaloy SO et al. Health-related incidence is similar to that reported in previous studies.
quality of life 1 year after allogeneic or autologous stem-celltransplantation: a prospective study. J Clin Oncol 1999; 17: In the present study, we have observed a lower adverse impact on QOL of RIC allogeneic as comparedto 10 Heinonem H, Volin L, Uutela A et al. Quality of life and autologous transplantation during the ﬁrst months after factors relatedto perceivedsatisfaction with quality of life transplant, which is due to a lower incidence of high-dose after allogeneic bone marrow transplantation. Ann Hematol chemotherapy-relatedtoxicity. By contrast, graft versus host disease remains an important ‘event’ in terms of QOL 11 Kiss TL, Abdolell M, Jamal N et al. Long-term medical among patients receiving RIC allogeneic transplant andits outcomes andquality of life assessment of patients with effect on QOL becomes evident at 9 months after chronic myeloidleukemia followedat least 10 years after transplantation. In conclusion, by the ﬁrst time point in allogeneic bone marrow transplantation. J Clin Oncol 2002; 20: the decision-making process, impairment of QOL does not 12 Neitzert CS, Ritvo P, Dancey J et al. The psychosocial impact hamper the allo-RIC approach as comparedto autologous of bone marrow transplantation: a review of the literature.
transplantation at least in the periodanalyzedin the Bone Marrow Transplant 1998; 22: 409–422.
current study. Studies analyzing QOL of these patients in 13 Kopp M, Schweigkoﬂer H, Holzner B et al. Time alter bone the long-term follow-up are warranted.
marrow transplantation as an important variable for quality oflife: results of a cross-sectional investigation using twodifferent instruments for quality of life assessment. AnnHematol 1998; 77: 27–32.
14 Syrjala KL, Chapko MK, Vitaliano PP et al. Recovery alter allogeneic marrow transplantation: prospective study of To Amelia de Leo´n andInmaculada Garcı´a-Palomero for their predictors of long-term physical and psychosocial functioning.
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15 Zittoun R, Suciu S, Watson M et al. Quality of life in patients with acute myelogenous leukemia in prolongedﬁrst completeremission alter bone marrow transplantation (allogeneic orautologous) or chemotherapy: a cross-sectional study of EORTC-GIMEMA AML 84 trial. Bone Marrow Transplant1997; 20: 307–315.
16 Andrykowski MA, Henslee-Downey PJ, Farral MG. Physical patients decide which choice is best. J Fam Pract 1997; 45: andpsychosocial functioning of adult survivors of allogeneic bone marrow transplantation. Bone Marrow Transplant 1989; 2 Silver RT, Woolf SH, Hehlmann R et al. An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and 17 Belec RH. Quality of life: perceptions of long-term survivors allogeneic bone marrow transplantation in treating the chronic of bone marrow transplantation. Oncol Nurs Forum 1992; 19: American Society of Haematology. Blood 1999; 5: 1517–1536.
18 Jenkins PL, Linington A, Whittaker JA. A retrospective study 3 Zittoun RA, Mandelli F, Willemze R et al. Autologous or of psychosocial morbidity in bone marrow transplantation allogeneic bone marrow transplantation comparedwith recipients. Psychosomatics 1991; 32: 65–71.
intensive chemotherapy in acute myelogenous leukaemia.
19 Slavin S, Nagler A, Naparstek E et al. Nonmyeloablative stem European Organization for Research andTreatment of Cancer cell transplantation andcell therapy as an alternative to (EORTC) andthe Gruppo Italiano Malattie Ematologiche conventional bone marrow transplantation with lethal cito- Maligne dell’Adulto (GIMEMA) Leukemia Cooperative reduction for the treatment of malignant and non malignant Groups. N Engl J Med 1995; 332: 217–223.
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21 Slevin ML, Plant H, Lynch D et al. Who shouldmeasure 5 Gianni AM, Bregni M, Siena S et al. High-dose chemotherapy quality of life, the doctor or the patient? Br J Cancer 1998; 57: andautologous bone marrow transplantation comparedwith MACOP-B in aggressive B-cell lymphoma. N Engl J Med 22 Aaronson NK, Ahmedzai S, Bergman B et al. The European organization for research andtreatment of cancer QLQ-C30: a 6 Philip T, Guglielmi C, Hagenbeek A et al. Autologous bone quality of life instrument for use in international clinical trials marrow transplantation as comparedwith salvage chemo- in oncology. J Natl Cancer Inst 1993; 85: 365–376.
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QOL in RIC allogeneic transplantationM Dı´ez-Campelo et al 25 McQuellon RP, Russell GB, Cella DF et al. Quality of life Appendix A: English version questionnaire measurement in bone marrow transplantation: development ofthe Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) scale. Bone Marrow Transplant1997; 19: 357–368.
Below is a list of statements that other people with your 26 Przepiorka D, Weisdorf D, Martin P et al. 1994 Consensus illness have saidare important. By circling one number per Conference on Acute GVHD Grading. Bone Marrow Trans- line, please indicate how true each statement has been for 27 Caballero MD, Rubio V, Rifo´n J et al. BEAM chemotherapy followedby autologous stem cell support in lymphoma Physical well-being (not at all, a little bit, some-what, quite patients: analysis of efﬁcacy, toxicity andprognostic factors.
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transplantation for Hodgkin’s disease: results and prognostic factors in 494 patients from the Grupo Espanol de Linfomas/ Because of my physical condition, I have trouble Transplante Autologo de Medula Osea Spanish Cooperative Group. J Clin Oncol 2001; 19: 1395–1404.
29 Caballero MD, Perez-Simon JA, Iriondo A et al. High-dose I am botheredby side-effects of treatment.
therapy in diffuse large cell lymphoma: results and prognostic factors in 452 patients from the GEL-TAMO Spanish Cooperative Group. Ann Oncol 2003; 14: 140–151.
Looking at the above 7 questions, how much would 30 Arnau J. Disen˜os longitudinales aplicados a las CC.SS. y del you say your Physical Well-Being affects your quality comportamiento. Limusa: Me´xico, 1995.
31 Kirk RE. Experimental Design: Procedures for the Behaviorial Sciences, (2ndedn) Brooks/Cole: Monterrey, 1982.
32 Maxwell SE, y Delaney HD. Designing Experiments and Social/family well-being (not at all, a little bit, some-what, Analysis of Data – A Model Comparison Perspective. Wads- worth Publishing Company: Beltmont, 1990.
33 Armitage JO. Bone Marrow Transplantation. N Eng J Med I get emotional support from my family.
I get support from my friends and neighbors.
34 Klingemann HG, Storb R, Fefer A et al. Bone marrow transplantation in patients aged45 years andold Family communication about my illness is poor.
35 Chiodi S, Spinelli S, Ravera G et al. Quality of life in 244 I feel close to my partner (or the person who is my recipients of allogeneic bone marrow transplantation. Br J Have you been sexually active during the past year? 36 HjermstadJR, Kaasa S. Quality of life in adult cancer patients No/Yes If yes: I am satisﬁedwith my sex life.
treatedwith bone marrow transplantation – a review of the Looking at the above seven questions, how much literature. Eur J Cancer Care 1995; 31A: 163–173.
wouldyou say your life Social/Family Well-Being 37 Pe´rez-Simo´n JA, Martino R, Alegre A et al. Chronic but not acute graft versus host disease improves outcome in multiplemyeloma patients after nonmyeloablative allogeneic transplan- Relationship with doctor (not at all, a little bit, some-what, tation. Br J Hematol 2003; 121: 104–108.
38 Vickberg S, Duhamel KN, Smith MY et al. Global meaning marrow transplant. Psycho-oncology 2001; 10: 29–39.
My doctor is available to answer my questions.
39 Andrykowski MA, Greiner CB, Altmaier EM et al. Quality of Looking at the above two questions, how much would life following bone marrow transplantation: ﬁndings from a you say your Relationship with the Doctor affects your multicenter study. Br J Cancer 1995; 71: 1322–1329.
40 Andrykowski MA, Carpenter JS, Greiner CB et al. Energy level andsleep quality following bone marrow transplantation.
Emotional well-being (not at all, a little bit, some-what, Bone Marrow Transplant 1997; 20: 669–679.
41 Hann DM, Jacobsen PB, Martin SC et al. Quality of life following bone marrow transplantation for breast cancer: a comparative study. Bone Marrow Transplant 1997; 19: 257– I am proudof how I’m coping with my illness.
I am losing hope in the ﬁght against my illness.
42 Whedon M, Stearns D, Millis LE. Quality of life of long-term adult survivors of autologous bone marrow transplantation.
Oncol Nursing Forum 1995; 22: 1322–1329.
I worry that my condition will get worse.
43 McQuellon RP, Craven B, Russell GB et al. Quality of life in Looking at the above six questions, how much would breast cancer patients before andafter autologous bone you say your Emotional Well-Being affects your marrow transplantation. Bone Marrow Transplant 1996; 18: 44 Syrjala KL, Chapko MK, Vitaliano PP et al. Recovering after allogeneic marrow transplantation: prospective study of Functional well-being (not at all, a little bit, some-what, predictors of long-term physical and psychosocial functioning.
Bone Marrow Transplant 1993; 11: 319–327.
I am able to work (include work in home).
My work (include work in home) is fulﬁlling.
I have concerns about my ability to have children.
I am enjoying the things I usually do for fun.
I am content with the quality of my life right now.
I regret having the bone marrow transplant.
Looking at the above seven questions, how much Looking at the above 12 questions, how much would wouldyou say your Functional Well-Being affects you say these Additional Concerns affect your quality Additional concerns (not at all, a little bit, some-what, quitea bit, very much) Additional items regarding GVHD symptoms: I am concernedabout keeping my job (include work in I worry that the transplant will not work.
The effects of treatment are worse than I had Pain hadinterferedin my daily activity.
MANAGEMENT OF CHRONIC PELVIC PAIN By Tim Chang o pain >6 months duration, o below the umbilicus o affecting daily activities accounts for 10% gynaecology visits 20% hysterectomies primary indication CPP 40% all laparoscopies performed fro CPP 40% cases there is NO obvious pathology in an adolescent there is increased likelihood of pathology∴ need to assess more aggressively A