tumour contamination and ease of acquisition. Although superiority in terms of an anti-tumour effect has yet to be

Transcription

1 Bone Mrrow Trnsplnttion, (1997) 20, Stockton Press All rights reserved /97 $12.00 Cost nlysis of the introduction of PBPC for utologous trnsplnttion: effect of switching from bone mrrow (BM) to peripherl blood progenitor cells (PBPC) C Bredeson 1, J Mlcolm 1, M Dvis 2, I Bence-Bruckler 1, B Kerns 1 nd L Huebsch 1 Divisions of 1 Hemtology nd 2 Administrtion, Ottw Generl Hospitl, Ottw, Cnd Summry: tumour contmintion nd ese of cquisition. Although superiority in terms of n nti-tumour effect hs yet to be Incresingly, PBPC insted of BM re used for utologous demonstrted, the short-term clinicl benefits of PBPC hve trnsplnttion. Limited dt exist on the economic led to its widespred doption in utologous trnspln- effects of this chnge. Using resource-bsed utiliztion ttion. model we prospectively determined the costs of 48 uto- With the incresed utiliztion of PBPC hs come the concern logous trnsplnts (eight BM, 17 BM + PBPC, 23 tht the incrementl cquisition costs of PBPC my PBPC), isolting the post-reinfusion period (dy 0 to not be offset by cost svings relted to quicker engrftment dischrge) to better determine the effect of the rescue nd shorter hospitl stys. This concern hs been prtilly product. Length of sty post-reinfusion ws significntly ddressed in series of retrospective studies, performed in shorter in ptients receiving PBPC (medin 13 dys) or heterogeneous ptient popultions, 3 6 nd more recently BM + PBPC (medin 14 dys) vs BM lone (medin 20 prospectively. 7 Clrifying the economic benefits of PBPC dys) (P 0.01). Accordingly, trnsplnt dmission however, requires tht the costs tht re dependent on the costs were less in the PBPC groups (PBPC $22 089, PBPC component (ie cquisition costs nd costs from dy BM + PBPC $23 179) vs the BM lone group ($32 289) of trnsplnt forwrd) re seprted from the totl costs of (P 0.05). Rescue product cquisition costs were higher the trnsplnt. These totl costs my vry significntly due for PBPC (rnge $3439 $5157) vs BM ($2766) but these to other fctors such s the conditioning regimen, which is costs were offset by the more rpid recovery of ptients chosen bsed on the disese being treted, tht re independent receiving PBPC. Overll trnsplnt costs depend on the of the rescue product. conditioning regimen with 10-fold cost vrition We previously developed costing model for utologous mong regimens. Modeled costs for utologus trnsplnttion trnsplnttion encompssing the different spects of the using vrious pproches to rescue product trnsplnt process including slvge chemotherpy, Hick- cquisition re given. The introduction of PBPC for mn line insertion, bone mrrow hrvest, PBPC collection utologus trnsplnttion hs resulted in cost svings t nd storge nd the ctul trnsplnt dmission. 8 This our institution. Although the cquisition costs of PBPC model took dvntge of our institution s on-line resource rescue product re greter thn for BM, this incremen- utiliztion-bsed ccounting system (Trnsition System 1; tl expense is more thn offset by less expensive postreinfusion Trnsition Sytems, Boston, MA, USA) to identify hospitl- period. relted costs in conjunction with the determintion of non- Keywords: cost nlysis; utologous trnsplnttion; hospitl costs such s professionl fees, blood product peripherl blood progenitor cells; grnulocyte colony- costs, nd the cquisition, processing nd storge of the stimulting fctor rescue product (BM or PBPC). We pplied this costing sys- tem to our utologous trnsplnt ptients s we moved from using BM lone to BM + PBPC to PBPC lone in the utologus High-dose therpy nd utologous trnsplnttion offers setting to determine the economic implictions of introducing PBPC. We specificlly wnted to isolte the mny ptients n incresed potentil of cure 1 or prolonged rescue product cquisition costs nd the post-reinfusion perdisese-free survivl 2 over lterntive therpies. Over the iod costs. In ddition, in order to determine the effect of pst severl yers, there hs been trnsition from the use differing pproches to utologous trnsplnttion we modof utologous bone mrrow (BM) to utologous peripherl eled the totl costs of utologous trnsplnttion using blood progenitor cells (PBPC) s the rescue product follow- vriety of pproches to rescue product cquisition. ing high-dose chemordiotherpy for vriety of resons, including superior rtes of engrftment for pltelets nd neutrophils, possible immunologic benefits, potentilly less Ptients nd methods Correspondence: Dr C Bredeson, Ottw Generl Hospitl, 501 Smyth Rd, Ottw, Ontrio, Cnd, K1H 8L6 Received nd ccepted 13 July 1997 From April 1993 to December 1994 ll ptients undergoing high-dose slvge therpy nd utologous trnsplnttion

2 Cost nlysis of PBPC vs BM in utologous trnsplnttion 890 for non-hodgkin s lymphom (NHL), Hodgkin s lym- tht could be met s n out-ptient (ie requiring no more phom (HD), or multiple myelom (MM) unresponsive to thn two trnsfusions per week) nd no other medicl prob- conventionl therpy were eligible for inclusion in the lems requiring them to remin in hospitl. Supportive cre study. Bone mrrow (BM) hd previously been collected nd dischrge prctices were consistent throughout the nd cryopreserved following recovery from slvge chemo- period of nlysis. therpy (DHAP, mini-beam or cyclophosphmide 4.5 g/m 2 ). Similrly, peripherl blood progenitor cells (PBPC) were collected during dily 2 or 3, 10-l leukphereses on Cobe Spectr (Cobe Lbortories, Lkewood, CO, USA) Cost nlysis following mobiliztion with the bove slvge chemotherpy regimens nd G-CSF (Neupogen; Amgen, Thou- As the purpose of the nlysis ws to determine the cost snd Oks, CA, USA) 5 g/kg/dy s.c. 9 dys. As prt implictions of using PBPC vs BM in vried pproches of phse 2 tril, severl ptients BM or PBPC were CD34 to utologous trnsplnttion, those spects relted to the selected using the Ceprte system (CellPro, Bothell, WA, trnsplnt tht re dependent on the rescue product or USA). The type of rescue product used in ny individul potentilly influenced by the rescue product re included. ptient reflects the progressive shift in prctice t our institution The trnsplnt-relted costs were determined for ech from using BM lone to BM nd PBPC in trn- ptient using model developed t our institution s pre- sition period to PBPC lone s we developed confidence viously reported. 8 Costs were determined from the perspec- in the reconstitutive potentil of PBPC. None of the BM- tive of the pyer gency (Ministry of Helth for the province only ptients hd PBPC collected, while some PBPC-only of Ontrio). For this nlysis, the components of the trnsplnt ptients hd bck-up mrrow stored. Ptients trnsplnt process for which costs were determined include received PBPC-only trnsplnts if the CD34 + cell count of BM nd PBPC collection, processing nd storge, the trns- the PBPC product ws /kg ptient weight. plnt dmission, blood product support nd professionl Ptients were conditioned pre-trnsplnt with one of severl fees. Other spects of the slvge progrmme including high-dose regimens depending on their dignosis nd insertion of the Hickmn line, slvge therpy dmissions, prior tretment history. Most ptients received CBV for HD pretrnsplnt pulmonry function testing nd crdic or MelVP16TBI 9 for low-grde NHL. Ptients with inter- MUGA scns re common to ll groups (BM, BM + PBPC medite-grde NHL received either regimen. Ptients with nd PBPC) nd unrelted to the ctul trnsplnt dmission multiple myelom were conditioned with BUCY regimens so they re not included in this nlysis. The cost of G- (BUCY ± TBI 500 cgy). All ptients received G-CSF CSF used in mobilizing PBPC is included in the PBPC ( 5 g/kg/dy s.c.) following reinfusion of utologous BM cquisition costs s G-CSF is not routinely used t our nd/or PBPC until the bsolute neutrophil count (ANC) ws centre following slvge chemotherpy /l. Actul G-CSF dose (300 or 480 g/dy) ws Hospitl-relted costs were determined using ctul bsed on the two vil sizes of Neupogen commercilly ptient resource utiliztion s cptured by the hospitl s on- vilble nd n ttempt to give 5 g/kg ptient weight. line ccounting system, the Trnsition System 1. This system Ptients were nursed on stndrd hospitl wrd with cptures ll ptient-specific direct (nurses etc) nd HEPA filters but without lminr irflow rooms. Pltelets indirect (overhed, lbortory technicins, supplies etc) (rndom or single donor) were trnsfused to mintin resources utilized in hospitl under number of cost centres pltelet count /l or if febrile (T 38 C) (nursing, phrmcy, lbortories etc). BM nd PBPC re /l nd pcked red blood cells (PRBC) were collected t our institution nd re processed t the Ottw given to mintin hemoglobin (Hb) 90 g/l. Blood pro- Centre of the Cndin Red Cross (CRC). The costs for ducts were irrdited. Twice weekly trimethoprim-sulfmethoxzole collection, processing nd storge of BM nd PBPC were ws given for pneumocystis pneumoni prophy- determined from both the Trnsition System 1 nd by lxis strting from dmission. Ptients received cyclovir determining ttributble costs for ech product processed t for HSV prophylxis. Whenever possible cyclovir ws the CRC. During the time of this study, within the Cndin given s the orl preprtion. No other prophylctic ntibiotics Helth Cre system, blood products were supplied to hospi- or nti-fungls were used routinely. Febrile neutro- tls by the CRC free of chrge. For purposes of the nly- peni (T 38 C nd ANC /l) ws treted with sis, costs for blood products were determined s the per either combintion of pipercillin nd tobrmycin or sin- unit cost for the CRC to supply these products multiplied gle gent therpy with third genertion cephlosporin. by the number of units of ech type of blood product util- Empiric vncomycin nd mphotericin B were dded fter ized per ptient. Appendix 1 lists the unit cost for severl 3 to 5 dys nd 5 to 7 dys, respectively, for persistent fever of these blood products. Professionl fees were determined despite the use of brod spectrum ntibiotics. Antimicrobil bsed on the provincil fee schedule for professionl services therpy ws further modified bsed on culture results. Antimicrobils supplied, including direct ptient cre nd relted were continued until neutrophil engrftment costs such s reporting of rdiogrphs etc. For the trnsplnt (ANC /l) nd defervescence. Ptients unble to sty, costs were collected for ech ptient from dy mintin n dequte orl cloric intke were fed whenever of dmission to dy of dischrge. possible vi nsogstric tube, or if necessry with totl The costs of CD34 + selection crried out s prt of prenterl nutrition. Ptients were dischrged from the hos- seprte phse 2 tril re not included s this ws not routine pitl once they were febrile, mbultory, hd neutrophil cre during the study period. In ddition, CD34 + selecpitl engrftment, dequte orl intke, trnsfusion requirements tion hs not been shown to ccelerte neutrophil or pltelet

3 Cost nlysis of PBPC vs BM in utologous trnsplnttion engrftment beyond tht of unselected PBPC. Lstly, the toxicity of PBPC infusion is minor whether selected or not Tble 1 Ptient demogrphics nd CD34 selection did not influence the length of sty during the period under nlysis. BM BM + PBPC PBPC Costs re reported in 1994 Cndin dollrs (1 Cn$ Gender Mle pproximtely equls 0.74 US$). Unit prices used for goods Femle nd services were those of our hospitl except for G-CSF. Age (yers) The unit cost of G-CSF used ws the mnufcturer s list Medin price. Appendix 1 lists the unit cost of mny of the common Rnge medictions nd lbortory tests included in the nlysis. Dignosis Hodgkin s lymphom Low-grde NHL Intermedite-grde NHL Sttistics High-grde NHL Multiple myelom Comprison mong the three groups for outcome dt (eg Conditioning CBV cost of trnsplnt dmission) ws done using n nlysis MelEtopTBI of vrince (ANOVA) for prmetric dt nd the Kruskl BUCY(TBI) 0 0 1(3) Wllis test for non-prmetric dt. Pirwise comprisons CyThio were done with Newmn Keuls or Dunn s multiple comprison test. Probbility of dischrge post-trnsplnt ws BM = bone mrrow only; BM + PBPC = bone mrrow nd peripherl determined using the product limit estimtes of Kpln nd blood progenitor cells; PBPC = peripherl blood progenitor cells only; NHL = non-hodgkin s lymphom; CBV = cyclophosphmide 7.2 g/m 2, Meier. Comprisons mong these probbilities to dischrge BCNU 300 mg/m 2, etoposide 2.4 g/m 2 ; MelEtopTBI = melphln 140 were mde with the Wilcoxon log-rnk test. For ll tests, mg/kg, etoposide 60 mg/kg, 500 cgy totl body irrdition in single P vlues were two-sided nd P 0.05 is considered s frction; BUCY = busulphn 16 mg/kg, cyclophosphmide 120 mg/kg; sttisticlly significnt. Anlysis ws conducted with Prism CyThio = cyclophosphmide 6 g/m 2, thiotep 600 mg/m 2. sttisticl softwre pckge (GrphPd Softwre, Sn Diego, CA, USA). ing PBPC nd BM lone in terms of neutrophil nd pltelet engrftment, dys on G-CSF, durtion of hospitl sty, nd Results dys from trnsplnt to dischrge (Tble 2). In ll cses the groups receiving PBPC (BM + PBPC or PBPC lone) hd Forty-eight ptients underwent utologous trnsplnttion superior results. For exmple, the medin number of dys nd received ll their cre t our institution during the study to neutrophils /l ws 12.5, 10 nd 9 in the BM, period. Four others were not included becuse they were BM + PBPC, PBPC groups respectively (P = 0.02). There trnsferred bck to nother centre on dy +1 s is our prcengrftment, length of hospitl sty, dys from trnsplnt ws no difference, however, in time to neutrophil or pltelet tice. As result cost dt were not vilble for this group. Of the 48 ptients, eight received BM only, 17 received to dischrge, dys of G-CSF or dys febrile between the BM + PBPC nd 23 PBPC lone. Tble 1 summrizes the groups receiving PBPC nd BM or PBPC lone (Tble 2). ge, sex, dignosis nd conditioning for these three groups. The number of dys to deliver ech conditioning regimen There ws no difference in medin ge of the three groups. vried from 6 to 8 (Tble 3). As result, the number of The proportion of ptients hving ech of the dignoses is dys in hospitl from dy 0, the dy of the rescue product not blnced mong the groups s the study ws not rndifferences between the rescue products. The time from res- infusion to dischrge better reflects the short-term clinicl domized but n nlysis of our prctice over period of time. Similrly, s the conditioning regimens re chosen cue product infusion to dischrge ws 20, 14 nd 13 dys bsed on the disese nd not the rescue product, the prorespectively. Agin there ws clinicl nd sttisticl dif- in the BM lone, BM + PBPC nd PBPC lone groups, portion of ptients receiving different conditioning regiference in fvour of the groups receiving PBPC vs the mens is not blnced mong the groups. As ll ptients received high-dose therpy nd the dignosis is not group receiving BM lone (P = 0.005) (Tble 2). The bene- expected to ffect post-trnsplnt recovery costs we felt fit of PBPC in shortening hospitl sty due to more rpid comprisons of the groups were vlid. The post-reinfusion engrftment nd clinicl recovery lthough evident by the G-CSF doses in g/kg ptient weight were 4.6, 4.5, 4.0 in shorter medin time from trnsplnt to dischrge is better the BM, BM + PBPC, PBPC lone groups, respectively, represented by looking t the probbility of dischrge post- nd were not sttisticlly different (P = 0.33). trnsplnt in the BM lone vs PBPC (Figure 1) where the effect of outliers cn be seen. Blood product requirements were low nd similr in ll three groups. There ws trend to lower numbers of pltelet Hemtologicl recovery nd morbidity trnsfusions in the PBPC groups (five single donor unit There were cliniclly nd sttisticlly significnt differences in pirwise comprisons between the groups receiv- equivlents) compred to the BM lone group (eight single donor unit equivlents) but this ws not significnt. 891

4 Cost nlysis of PBPC vs BM in utologous trnsplnttion 892 Tble 2 Outcome post-trnsplnt BM BM + PBPC PBPC Length of sty (dys) medin rnge Length of sty post-trnsplnt (dys) medin 20 b BM lone rnge PBSC groups Dy ANC /l medin rnge Dy pltelets /l c Dys medin P = by logrnk test rnge Dys febrile (T 38 C) Figure 1 Probbility of dischrge post-utologous trnsplnttion. medin rnge Units PRBC trnsfused medin Costs rnge Units pltelets trnsfused d Trnsplnt dmission medin The cost of the trnsplnt is composite of the hospitl rnge sty-relted costs bsed on resource utiliztion, the cost of Dys G-CSF blood products used s supportive cre, professionl fees medin rnge nd the cost of supplying the rescue product. The costs of the trnsplnt excluding the cost of the rescue product were Dily G-CSF dose ( g/kg) men higher in the BM lone group (medin $32 289) compred s.d to the groups receiving either BM + PBPC (medin $23 179) or PBPC lone (medin $22 089). This difference P 0.05 vs other groups in pirwise comprison using Newmn Keuls. occurs predomintely post-reinfusion (from dy 0 to b P 0.01 vs other groups in pirwise comprison using Dunn s multiple dischrge) (medin BM $21 567; BM + PBPC $13 945; comprison test. c PBPC $13 189) which better reflects the direct effect of the Without trnsfusion support. d Units of pltelets = No. units single donor pltelets + (No. units rndom rescue product (Tble 4) nd removes the vribility in the donor pltelets)/5. number of dys nd costs of the different conditioning regi- ANC = bsolute neutrophil count. mens (Tble 3). The effect of the vrying conditioning regimens on overll costs reltes both to the number of dys over which they re dministered nd the unit costs of the component chemotherpeutic gents nd TBI (Tble 3). The most expensive regimens by severl-fold re those contining Tble 3 Administrtion dys nd costs of conditioning regimens etoposide while the lest expensive conditioning regimen is stndrd BUCY ($563 per course). Dys MD fees Phrmcy costs Totl b The cost of the rescue product depends on multiple fc- ($) ($) tors in ddition to whether BM or PBPC re used lone or Men s.d. ($) ($) Probbility MelEtopTBI c CBV BUCYTBI c BUCY CyThio Tble 4 Trnsplnt dmission costs from reinfusion until dischrge BM BM + PBPC PBPC n = 8 n = 17 n = 23 Dys = chemotherpy dministrtion dys + rest dys. b Totl = MD fee + men phrmcy fee. c For TBI, rdition oncologist fees re included with MD fee nd TBI costs with phrmcy. Minimum Medin b Mximum All vlues given s Cndin dollrs. Costs include hospitl-relted costs, costs of blood products, MD fees. b P 0.05 by Dunn s multiple comprison for pirwise comprisons of BM vs BM + PBPC or PBPC.

5 Tble 5 Rescue product cquisition costs G-CSF dose ( g/dy) Number of phereses BM PBPC + BM PBPC All vlues in Cndin dollrs. Costs = hospitl costs for BM hrvest or phereses + G-CSF 9 dys + MD fees + processing nd storge costs. Cost nlysis of PBPC vs BM in utologous trnsplnttion Phrmcy 44% Imging 1% Lbortories 9% Physicin 8% 893 in combintion (Tble 5). The costs of hrvesting nd storing BM re firly uniform nd consist of the hospitlrelted costs of the hrvest procedure, professionl fees of the hrvesting physicin nd nesthetist, s well s the processing nd storge costs. The costs of PBPC re more vrible nd depend on the number of dys nd dose of G- CSF used in mobilizing, the weight of the ptient, the number of phereses performed to collect n dequte number of PBPC nd the costs of processing nd storing the collected product. In order to reflect these vribles we constructed series of modeled results (Tble 6) which consist of the trnsplnt costs without the stem cell product s reported bove plus the cquisition costs for the different rescue products (Tble 5) bsed on G-CSF dose nd dys of phereses. The costs of the rescue product rnge from $2766 for BM lone to $5157 for 9 dys of 480 g G-CSF nd three phereses. The use of these together would result in rescue product costing $7923. With ll the rescue products modeled, the dditionl cquisition cost of PBPC is less thn the svings they relize through fster engrftment nd shorter hospitl stys (Tble 6). A brekdown of the trnsplnt sty by cost centre is depicted in Figure 2. In ll three groups (BM, BM + PBPC, PBPC) even though there were differences between the totl cost of the trnsplnt dmission, the proportion tht ws ttributble to ech cost centre (nursing, phrmcy, lbortories etc) ws the sme. The combintion of nursing nd phrmcy ccounted for pproximtely 74% of the trnsplnt sty costs in ll three groups. Similrly, for ll Nursing 31% Red Cross 7% Figure 2 Percentge cost of utologous trnsplnt by cost centre. The distribution of costs ws the sme in ll three groups (BM, BM + PBPC, PBPC), lthough the ctul dollr vlues differed. groups, the conditioning regimen mde up the lrgest proportion of the phrmcy costs (pproximtely 45%), the post-trnsplnt G-CSF contributed 17% nd the reminder ws due to other spects of supportive cre including nti- emetics nd ntibiotics. Discussion The min purpose of our study ws to determine clinicl nd economic effects of vried pproches to utologous trnsplnttion following the introduction of PBPC into prctice t n verge-sized Cndin trnsplnt pro- grmme. While the efficcy of uto-pbsc hs been estblished, the cost-effectiveness of PBSC with their higher cquisition costs remins unresolved compred to BM. There re severl spects of our study tht re result of our progrmme being in Cnd nd our institution hving n on-line resource utiliztion bsed ccounting system. The min benefit to our study is tht the difficulty of differentiting costs from chrges 10 s occurs in mny Americn Tble 6 Modeled costs of utologous trnsplnttion bsed on rescue product G-CSF for PBPB BM No. Phereses Minimum Medin Mximum mobiliztion ( g/dy) 0 yes yes yes yes yes no no no no All vlues in Cndin dollrs. Costs = rescue product cquisition costs (Tble 5) + trnsplnt dmission costs (Tble 4). BM = bone mrrow; PBPC = peripherl blood progenitor cells.

6 Cost nlysis of PBPC vs BM in utologous trnsplnttion 894 studies does not exist within the Cndin Helth cre sys- norml levels. Similrly, while totl trnsplnt costs re tem. Cndin hospitls function primrily within single useful crude estimte of the cost benefits of PBPC, vri- pyer gency system nd function s non-profit institutions. tions in pre-reinfusion prctice my significntly influence The pyer gency, the Ministry of Helth for Ontrio, pys totl costs nd bis the results in fvour of or ginst for services provided to in-ptients. Although supplementl prticulr pproch. In our study, conditioning costs vried insurnce is common for ptients, it does not ffect wht significntly depending on the regimen chosen. This ws the Ministry of Helth pys the hospitls for in-ptient ser- in prt due to the number of dys over which prticulr vices. The sme pplies to physicin billings. Extr billing, regimen is given, but more significntly due to the differ- the chrging of fees bove the provincil schedule within ence in cost of the different chemotherpeutic gents. For the Ontrio Helth Insurnce Pln, is prohibited. exmple t our institution, MelVP16TBI ($6701) costs The use of n on-line resource utiliztion bsed ccount- more thn 10 times s much s BUCY ($563). As the conditioning ing system enbles us to determine more ccurtely wht regimen is chosen bsed on the dignosis nd not n individul sty costs the helth cre system. Finlly, to the rescue product, these costs should be isolted when performing lrge extent the Cndin helth cre system is less driven cost nlysis of PBPC vs BM. In ddition, until by medicl legl concerns thn its Americn counterprt. there is convincing evidence of superiority of one regimen As result, the prctice pttern with regrds to tests nd over nother, the choice of conditioning regimen remins supportive cre is less exhustive. Nonetheless, lthough n opportunity for cost reduction t centres needing to control our results in totl dollrs re significntly less thn results totl progrmme costs. reported from mny Americn institutions, nd this is in Although the trnsplnt dmission costs s reported here prt due to differences in prctice style, the use of unit costs nd elsewhere 3 7 re firly homogeneous with PBPC, the nd resource utiliztion bsed costs should enble other cost of the rescue product vries significntly depending on institutions to compre their prctice ptterns nd unit costs wht is used. As it is not possible lwys to use the sme with our results. Precise inter-institutionl or interntionl product (eg inbility to hrvest BM if prior pelvic comprisons of trnsplnt costs, however, remins problemtic irrdition) nd ptient size influences rescue product due to differences in ccounting prctices nd over- cquisition costs, we modeled the cost of the rescue product hed mong centres. Furthermore, s competition mong bsed on differing numbers of phereses, vil size of G-CSF, trnsplnt centres in Americ incresingly includes cost nd whether PBPC, BM or both were utilized. In ll models, long with qulity, significnt reductions in trnsplntrelted the cquisition costs of PBPC in the rescue product chrges nd costs re beginning to be relized. ($3439 $5157) were offset by the svings relized through The clinicl benefits of shorter engrftment times previously their use s result of fster hemtologicl recovery postcohort reported with PBPC hve been confirmed in our trnsplnttion. The use of such modeling llows centres of ptients. Initil concerns tht PBPC my not beginning trnsplnt progrmme or centres nlyzing the result in sustined engrftment led to their use s n djunct costs of their progrmme to estimte for popultion of to BM in utologous trnsplnttion. Experience, however, ptients wht the costs of the vrious pproches would be indictes tht to dte this concern is unfounded. This hs better thn ssigning one cost per trnsplnt vlue. Obviously, led to the use of PBPC lone in mny centres. Within our in some situtions such s filure to mobilize, the study the use of BM in ddition to PBPC ws not ssocited cost of PBPC collection would not be offset by their use with ny clinicl dvntge but n dditionl cost of but this represents smll frction of ptients nd could be pproximtely $2800 per trnsplnt. If no bck-up BM is included in progrmme s overll cost model. required, this cost cn be eliminted. Another dvntge to While other spects of cre will influence the overll PBPC is reflected in the erly dt indicting tht ptients costs of the trnsplnt, the costs of the trnsplnt dmission who hve experienced donting both generlly prefer re driven by nursing nd phrmcy. In our study, inde- donting PBPC over BM. 9 pendent of the pproch used, nursing ccounted for As indicted erlier, to best determine the impct of pproximtely 30% of trnsplnt dmission costs while PBPC it is necessry to isolte clinicl effects nd costs phrmcy ws 45%. Of phrmcy costs, conditioning ws tht re ttributble to their use. This is best represented 45% nd post-trnsplnt G-CSF 20% in the BM groups by the intermedite outcome time from reinfusion to dis- nd 15% in the PBPC groups. All other spects of phrmcy chrge. In our study the time from reinfusion (dy 0) to ccounted for 25% of trnsplnt dmission costs. dischrge ws significntly shorter, pproximtely 7 dys Further efforts t mking uto-trnsplnttion more economicl in the PBPC groups. The time difference ws greter thn will hve to look t wys of reducing those two simply the difference in the number of dys to neutrophil components by moving trnsplnts to the out-ptient setting (ANC, /l) or pltelet ( /l) engrftment. s is now the prctice t our institution, nd s before, The dvntge seen in time to dischrge with PBPC is more potentilly reconsidering wht conditioning regimen is likely relted to the rpid rise of neutrophils to norml or being used. Conversely, other spects of long-term outcome suprnorml levels seen with PBPC compred to BM nd my dversely ffect short-term choices if delyed toxicities not simply the more rpid chievement of /l neutrophils. re more common or serious with the regimen hving Resolution of fever, infections nd probbly muco- the lest up-front costs. Future economic nlyses will need sitis occur with less vrition following utologous trnsplnttion to consider these vribles s more dt become vilble. with PBPC compred to BM where some Comprison of our results with those published recently ptients hve slow clinicl recovery with neutrophil counts by Smith et l 7 highlights both the difficulties of inter-insti- t or round /l for mny dys prior to returning to tutionl comprisons nd the overll similrity of results

7 Cost nlysis of PBPC vs BM in utologous trnsplnttion when contrsting BMT nd PBPCT. The first difference is logous trnsplnttion remins cost-effective therpeutic in the currency reported with our costs (1994 Cn$) equl option for mny ptients. to $ US. More importntly, significnt mngement prctice differences between the two studies including neutrophil level for stopping G-CSF, dischrge criteri, use of prenterl nutrition, ICU stys nd in-ptient dys for Acknowledgements grft procurement mke direct detiled comprisons difficult. The overll results, however, re quite similr. Both This project ws supported in prt by Amgen Cnd Inc. studies identify 25% svings with PBPCT vs BMT s did Bennett. 11 The reporting of unit costs while different in formt in the two reports llows some contrsting of costs to References identify if both centres hve similr cost drivers. Grft 1 Philip T, Guglielmi C, Hgenbeek A et l. Autologous bone procurement ccounted for 15% in the Smith study nd mrrow trnsplnttion s compred with slvge chemobetween 10 15% for BM or PBPC in our study depending therpy in relpses of chemotherpy-sensitive non-hodgkin s on dose of G-CSF nd number of phereses. Conditioning lymphom. New Engl J Med 1995; 333: therpy in the Smith pper ppers to be pproximtely 2 Bezwod WR, Seymour L, Dnsey RD. High-dose chemo- twice the cost of similr regimens in our institution bsed therpy with hemtopoietic rescue s primry tretment for primrily on per diem. Although not reporting on identicl metsttic brest cncer: rndomized tril. J Clin Oncol 1995; 13: ptients or prctice ptterns, the results nd conclusions re 3 Fucher C, le Corroller AG, Blise D et l. Comprison of the sme tht PBPCT is more cost-effective thn BMT. G-CSF-primed peripherl blood progenitor cells nd bone Other considertions beyond cost must lso be mde mrrow uto-trnsplnttion: clinicl ssessment nd costwhen ultimtely choosing which rescue product to use in effectiveness. Bone Mrrow Trnsplnt 1996; 14: support of high-dose therpy. More rpid immune reconsti- 4 Ager S, Scott MA, Mhendr P et l. Peripherl blood stem tution, potentilly less tumour contmintion in the grft, cell trnsplnttion fter high-dose therpy in ptients with ptient preference nd decresed morbidity hve ll been mlignnt lymphom: retrospective comprison with uto- reported with PBPC. 12 Difficulties with venous ccess, fil- logous bone mrrow trnsplnttion. Bone Mrrow Trnsplnt ure to mobilize PBPC nd lingering concerns regrding the 1995; 16: Uyl-de-Groot CA, Richel DJ, Rutten FFH. Peripherl blood use of G-CSF in myeloid mlignncies my still fvor the progenitor cell trnsplnttion mobilised by r-methug-csf use of BM in some ptients. (filgrstim); less costly lterntively to utologous bone mr- The results of this nlysis must be tken in the context row trnsplnttion. Eur J Cncer 1994; 30A: of stndrd trnsplnts performed without purging or 6 Gulti SC, Bennett CL. Grnulocyte mcrophge colony-stimulting other mnipultions such s ex vivo expnsion of PBPC or fctor (GM-CSF) s djunct therpy in relpsed post-reinfusion immune modultion. While these reserch Hodgkin disese. Ann Intern Med 1992; 116: procedures generlly increse the cost of the trnsplnt, the 7 Smith TJ, Hillner BE, Schmitz N et l. Economic nlysis of continued serch for optiml therpy should tke preperipherl-blood-progenitor-cell trnsplnttion nd utolog- rndomized clinicl tril to compre filgrstrim-mobilized cedence over cost considertions. Once n pproch is ous bone mrrow trnsplnttion in ptients with relpsed found to be of clinicl benefit, efforts cn be mde to study Hodgkin s nd non-hodgkin s lymphom. J Clin Oncol 1997; nd improve upon its economic implictions. Alterntive 15: pproches such s G-CSF stimulted BM 10 my result in 8 Bredeson C, Mlcolm J, Dvis M et l. Comprehensive cost the sme short-term clinicl benefit nd would therefore nlysis of innovtion in high-dose therpy nd utologous be expected to hve similr cost effectiveness. Ex vivo trnsplnttion. Blood 1994; 84: 493 A1958 (Abstr.). expnsion, lthough expected to be ssocited with signifiside, melphln, totl body irrdition nd ABMT in ptients 9 Keting A, Rubinger M, Sutcliffe S et l. High-dose etopo- cnt up-front costs, my enble brogtion of post-reinwith hemtologic mlignncies. In: Dicke KA, Spitzer G, fusion neutropeni nd thrombocytopeni, resulting in Jgnnth S (eds). Autologous Bone Mrrow Trnsplnttion. improved outcome nd net economic benefit. As the field 1989, pp continues to undergo rpid evolution, these types of econ- 10 Jnssen WE, Perkins J, Hiemenz JW et l. Grnulocyte recovomic studies will become more difficult to perform with ery is not different following uto-trnsplnt with G-CSF significnt ptient numbers. Similrly, the externl vlidity primed bone mrrow or G-CSF mobilized peripherl blood of ny single institutions pproch my be incresingly lim- stem cells. Blood 1994; 84: 95 (Abstr. 367). ited. As result, the role of economic modeling bsed on 11 Bennett CL, Armitge JL, Armitge GO. Costs of cre nd outcomes for high-dose therpy nd utologous trnsplnccurte but limited mounts of rel ptient dt, resonble ttion for lymphoid mlignncies: 1987 through J Clin ssumptions bout risks, benefits nd costs, sensitivity Oncol 1995; 13: nlyses round these ssumptions will become greter s 12 Kessinger A. Do utologous peripherl blood cell trnsplnts the implictions of vrious pproches to trnsplnttion provide more thn hemtopoietic recovery? Stem Cells 1995; re considered within the societl context. Until then, uto- 13:

8 896 Appendix 1 Cost nlysis of PBPC vs BM in utologous trnsplnttion Smple unit costs in nlysis Cost/Unit Professionl fees BM hrvest /hrvest Pheresis 14.10/pheresis BM/PBPC infusion 57.50/infusion Dy +1 to dy MD dily visit 17.10/visit Nurse 82.40/h Blood products Pcked RBC 86.00/unit Single donor pltelets /bg Rndom donor pltelets 26.00/bg Lbortory Complete blood count 7.80/test Pltelet count 8.00/test Differentil 16.40/test Chem /test Routine blood culture 34.00/test Imging Chest X-ry (two views) 36.00/test Ultrsound bdomen /test Ultrsound pelvis 95.00/test Phrmcy b G-CSF 300 g c /vil G-CSF 480 g c /vi Etoposide d /g Melphln d /cycle MelVP16TBI Crmustine d /cycle CBV Ondnsetron 12 mg i.v /dose 8 mg/i.v /dose 8 mg p.o /dose Acyclovir 800 mg p.o. 6.80/dose 500 mg/i.v 46.50/dose Ceftzidime 1 2 g 38.50/dose Vncomycin 1 g 37.90/dose Tobrmycin 100 mg 11.00/dose Ceftrixone 1 g 56.00/dose All costs in Cndin dollrs. Exception for professionl fees, costs re hospitl-relted costs only nd do not include MD fees where pplicble. Cndin Red Cross costs to supply products. b All phrmcy costs given s totl product cost. Lbour nd supplies dded per unit s follows: IV chemotherpy $31.40/dose, non-chemotherpy IV $3.60. c G-CSF retil price. d Unit cost bsed on TSI system which determines unit cost bsed on totl volume purchsed nd verge cycle dose.