Assessment of the Clinical Performance of Platelet Concentrates Treated by Pathogen Reduction Technology in Santiago de Compostela

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1 Originl Artile Trnsfus Med Hemother 2017;44:5 9 DOI: / Reeived: Februry 10, 2016 Aepted: June 10, 2016 Published online: Otober 28, 2016 Assessment of the Clinil Performne of Pltelet Conentrtes Treted by Pthogen Redution Tehnology in Sntigo de Compostel M. Dolores Vilriño Azuen Cstrillo b Alfredo Cmpos Rhel Kilin Meredes Villmyor Mri Crdoso University Clini of Sntigo de Compostel, Sntigo de Compostel, Spin; b Blood Trnsfusion Center of Glii, Sntigo de Compostel, Spin; Terumo BCT Europe, Zventem, Belgium Keywords Riboflvin-bsed pthogen redution Pthogen redution Clinil performne Summry Introdution: This study ssessed the fesibility, performne, nd sfety of Mirsol -treted pltelet onentrtes (M-PC) stored for up to 7 dys. Methods: This prospetive observtionl study ws pproved by the ethil ommittee of the University Clini of Sntigo de Compostel. Informed onsent ws sked from ptients reeiving M-PC. M-PCs were treted with the Mirsol system ording to the mnufturer s instrutions. Thromboytopeni ptients were trnsfused ording to the Spnish trnsfusion guidelines. Post-trnsfusion pltelet ounts were mesured t 1 h nd/or 24 h fter trnsfusion. Post-trnsfusion surveillne of ptients ws mintined during the study. Results: Dt from 54 evluble ptients nd 135 trnsfusions were nlyzed. The men ge of ptients ws 58 yers. The men ge of M-PC t trnsfusion ws 3.6 dys. The men pltelet dose ws The trnsfusion responses mesured s men orreted ount inrement 1 h fter trnsfusion (CCI 1h ) nd CCI 24h were 9,659 nd 4,751, respetively. 65% of trnsfusions resulted in CCI 1h vlues 7, % of trnsfusions resulted in CCI 24h vlues 4,500. Conlusion: The use of M-PC in the supportive tretment proved to be sfe nd effetive for this ohort of thromboytopeni ptients S. Krger GmbH, Freiburg Introdution A sfe nd stble blood supply is prmount for funtionl helth system [1]. Regultory genies, blood providers nd medil professionls re ontinuously implementing nd improving mesures tht n gurntee sfe blood supply. Muh of this effort ws initited in the fe of emerging infetious threts in the blood supply, s exemplified by the experiene with HIV. Despite the implementtion of the HIV blood sreening test, one of the most suessful retive sfety mesures ever implemented, soiety still hd to py high prie in terms of humn lives nd helth s result of not being prepred for the emergent pndemi of AIDS [2]. This experiene only emphsized the ft tht, lthough zero risk for blood trnsfusion is unttinble [3], provision of the sfest blood possible must remin one of the biggest ommitments of world poliy [4]. Modern times re hrterized by intense world trvel, migrtion, nd inresed globl ommeril interdependene (globliztion). These ftors dd to demogrphi hnges nd ontribute to the omplexity of the tsk of mintining sfe blood [5]. Spin pioneered the use of pthogen redution tehnology (PRT), initilly for the tretment of fresh frozen plsm (FFP) [6]. The pplition of this protive risk redution mesure ws ment to ontin the dissemintion of infetious diseses in times of ontinuous threts, s seen with reent exmples suh s HIV/AIDS, severe ute respirtory syndrome (SARS), hikunguny nd dengue outbreks s well s West Nile virus infetions. The Blood Trnsfusion Center of Glii supplies blood to 31 hospitls nd popultion of bout 2.7 million inhbitnts in the Northwestern region of Spin. It ollets pproximtely 105,000 whole blood nd 6,700 pheresis dontions per yer. Sine 1998, Fx Informtion@Krger.om S. Krger GmbH, Freiburg Aessible online t: Dr. Mri Dolores Vilriño Hospitl Clinio Universitrio de Sntigo de Compostel Plz de Ultrei, n 13, 2 dereh Sntigo de Compostel, Spin mdvl-heis@hotmil.om

2 Tble 1. Ptient groups trnsfused with M-PC during the observtion period Totl Aute leukemi NHL HL MDS Mrrow plsi Multiple myelom Ptients Non-hemtologil diseses Trnsfusions NHL = Non-Hodgkin s lymphom; HL = Hodgkin s lymphom; MDS = myelodysplsti syndrome. Fig. 1. Sttistil nlysis to hek equivlene of mesurements by three different ell ounters. FFP hs been treted with the Therflex Methylene Blue system (MoPhrm, Lngen, Germny) before trnsfusion. Pltelet onentrtes hve been treted with the INTERCEPT PRT System (Cerus Corp, Conord, CA, USA) sine Reently, the Blood Trnsfusion Center of Glii ssessed the qulity of Mirsol PRT-treted (Terumo BCT, Lkewood, CO, USA) pltelet onentrtes (M-PC) nd stored in pltelet-dditive solution for up to 7 dys [7]. This tehnology uses riboflvin (vitmin B 2 ) nd UV light to redue the pthogen lod nd to intivte ontminting white blood ells in blood omponents. Results of this study demonstrted eptble pltelet qulity, whih prompted the Blood Trnsfusion Center nd the University Clini of Sntigo de Compostel to strt linil study to investigte the performne of these produts in the supportive therpy of thromboytopeni ptients. The study ws designed to ssess the fesibility, performne, nd sfety of M-PC stored for up to 7 dys. Ptients nd Methods Ethil Committee Approvl nd Ptient Consent The protool for prospetive observtionl study ws submitted to the ethil ommittee of the University Clini of Sntigo de Compostel nd grnted pprovl before the strt of the study. Ptients reeiving M-PC hd to sign n informed onsent form before strting therpy. Preprtion of Buffy Cot-Derived Pltelet Conentrtes nd Mirsol PRT Tretment Pltelet onentrtes proessed from whole blood olletions with the OrbiS tehnology (Terumo BCT) were treted with the Mirsol PRT system ording to the mnufturer s instrutions for use. After tretment, M-PC were immeditely relesed with no dditionl tretment. Pltelets solved in the pltelet-dditive solution SSP+ (Mophrm) originted from 5 buffy ot pools nd were stored up to 7 dys t 22 C on n gittor. Blood proessing nd tretment were done ording to protool desribed in n erlier publition [7]. Ptients Exlusively stble thromboytopeni ptients were enrolled in this study. These ptients were mintined on prophylti pltelet-supportive therpy ording to the Spnish nd interntionl trnsfusion guidelines, s well s in ordne with the institution s stndrd prties. Only ptients over the ge of 18 reeiving t lest 1 U of M-PC were inluded in the study. Ptients were exluded if they were refrtory to pltelet trnsfusion, if they showed tive bleeding, if trnsfusion ws needed during surgery, or if the informed onsent form hd not been signed. Ptients reeived ABO/Rh group-omptible pltelets. Pltelet Trnsfusions Post-trnsfusion pltelet ounts were mesured t 1 h nd/or 24 h fter trnsfusion. Furthermore, post-trnsfusion surveillne of ptients ws mintined during the study period. All sttistil nlyses were onduted using SAS/BASE, SAS/STAT softwre, version 9.4 of the SAS System for Windows (SAS Institute In., Cry, NC, USA). Cell Counting Cell ounters from three deprtments were used: Sysmex XT (Sysmex, Norderstedt, Germny) t the Blood Trnsfusion Center) COULTER AT 6 Trnsfus Med Hemother 2017;44:5 9 Vilriño/Cstrillo/Cmpos/Kilin/Villmyor/ Crdoso

3 Fig. 2. Observed rtes of suessful trnsfusions, using thresholds of CCI1h 7,500 nd CCI24h 4,500. 5diff CP (Bekmn Coulter Life Sienes, Indinpolis, IN, USA) t the emergeny deprtment, nd Advi 2120i (Siemens Helthineers, Erlngen, Germny) t the hemtology deprtment. The Clibrtion of the three ell ounters ws performed by testing undiluted smples from the sme pltelet onentrte (N = 38) prior to initition of the study protool. Sttistil nlyses were performed by mens of Sttsoft In. (2012) STATISTICA (dt nlysis softwre system), version 12 (Dell Sttisti, Tuls, OK, USA). Mtrix plotting ws used to ssess the distribution nd the regression for the vrious ounter ombintions. R-vlues ll showed eptble ounter orreltions. Pltelet Performne Assessment Post-trnsfusion pltelet ounts were mesured t 1 h nd/or 24 h fter trnsfusion. CI (ount inrement) nd CCI (orreted ount inrement) were lulted using the following formuls (BSA = body surfe re): CI 1h = (1-hour post-trnsfusion pltelet ount) (pre-trnsfusion pltelet ount) (1), CI 24h = (24-hour post-trnsfusion pltelet ount) (pre-trnsfusion pltelet ount) (2), CCI 1h = (CI 1h / trnsfused pltelet dose) BSA (3), CCI 24h = (CI 24h /trnsfused pltelet dose) BSA (4), BSA = height weight (5). Results Pltelet Conentrtes Treted by Mirsol PRT The men yield of trnsfused M-PC ws , rnge , stndrd devition (SD) The men ge of M-PC t the time of trnsfusion ws 3.6 dys, rnge dys, SD 0.1 dys. Nerly 90% (89.4%) of pltelets were trnsfused t dys 1 5, the remining 10.6% were trnsfused t dys 6 nd 7. Ptients 55 ptients were enrolled initilly. One ptient ws exluded due to refrtoriness. In totl, trnsfusion dt from 54 ptients nd 135 trnsfusions were nlyzed. The men ge of ptients ws 58 yers (rnge yers). 55% of ptients were mle. Tble 1 shows ptients grouped by dignosis: ute leukemi inluding Tble 2. Pltelet performnes s mesured by CCI1h nd CCI24h per ptient group Aute leukemi NHL b HL MDS Mrrow plsi MM Non-hemtologi l d CCI1h CCI24h CCI1h CCI24h CCI1h CCI24h CCI1h CCI24h CCI1h CCI24h CCI1h CCI24h CCI1h CCI24h Number of pltelet produts trnsfused 6,409 13,200 (6,979) 8,800 (3,897) 9,560 (8,810) 4,815 (3,038) 10,828 (2,968) 5,030 (6,500) 1,544 (3,170) 7,288 (2,885) 5,920 (7,250) 7,592 (1,065) 3,282 (3,355) Men (SD) 9,262 (6,248) 15,235 (3,662 18,020) 7,110 (1,770 16,308) 9,560 (3,330 15,970) 3,880 (3,033 8,300) 9,270 (8,960-14,250) 2,100 ( 2,490 16,540) 494 ( 1,777 8,900) 8,250 (3,150 9,500) 4,240 ( 3,330 3,1350) 8,600 (3,000 3,510) 3,445 ( 3,500 to 5,800) Medin (rnge) 8,403 (0 17,960) HL = Hodgkin s lymphom; MDS = myelodysplsti syndrome; MM = multiple myelom; NHL = non-hodgkin s lymphom. Aute leukemi, inluding ute lymphoblsti leukemi (ALL) nd ute myeloid leukemi (AML). b NHL, inluding B-ell lymphom. Mrrow plsi, inluding plsi nd hypoplsi. d Non-hemtologil, inluding post-rdi surgery nd liver irrhosis. Clinil Performne of PRT-treted Pltelet Conentrtes Trnsfus Med Hemother 2017;44:5 9 7

4 ute lymphoblsti leukemi (ALL) nd ute myeloid leukemi (AML), non-hodgkin s lymphom (NHL) inluding B-ell lymphom, Hodgkin s lymphom (HL), myelodysplsti syndrome (MDS), mrrow plsi inluding plsi nd hypoplsi, nd nonhemtologil diseses inluding post-rdi surgery nd liver irrhosis. Clinil ftors tht led to inresed pltelet onsumption were bsent only in 32% of the enrolled ptients. Most of the suseptible ptients showed symptoms of fever nd/or infetion (24%) or hd reently undergone bone mrrow trnsplnttion (31%). Clibrtion of Cell Counters Dt mesured from identil smples by the three different ell ounters ppered to be normlly distributed (Shpiro-Wilk; p > 0.05 for ll), s demonstrted in figure 1. The three popultions mesured on the three ounters were found to be normlly distributed (Shpiro-Wilk; p > 0.05). ANOVA reveled no differene between the ounters (p = 0.4). Desriptive sttistis, vribility plotting, nd box plotting showed similr popultion distributions for ll ounters. Hene, dt olleted by the ounters ould be used without ny further librtion or extrpoltion. Pltelet Performne The men number of trnsfusions per ptient ws 2.5, rnge 1 6, SD 1.5, medin 2.0. Considered together, the observed men of ll trnsfusions CCI 1h (n = 23), nd CCI 24h (n = 120) ws 9,658 nd 4,751 (tble 2). 65% nd 42% of trnsfusions showed CCI levels bove the interntionlly epted threshold for suessful trnsfusions of 7,500 for CCI 1h nd 4,500 for CCI 24h (fig. 2). Bsed on the men vlues of CCIs, trnsfusion responses were lower thn thresholds in ptients with ute leukemi (CCI 24h ) nd HL (CCI 24h ) (fig. 2b). Two ute trnsfusion retions of grde I with imputbility onsidered possible were observed during 135 trnsfusions. Disussion The Mirsol PRT tehnology ws prtilly implemented t the Blood Trnsfusion Center of Glii to gurntee the ontinuous supply of M-PC to the Deprtment of Hemtology nd Hemotherpy of the University Clini of Sntigo de Compostel during the study period. Due to its simpliity, eduting opertors nd implementing the tehnology went very smoothly, with treted produts being relesed erlier thn the ones treted with lterntive tehnology employed t the site sine In this study, linil performne of M-PC ws evluted by post-ount inrement determintion fter prophylti trnsfusion of thromboytopeni ptients. Previous studies ould show ler reltionship between trnsfusion filures, defined s inrements below interntionl reognized thresholds, nd bleeding omplitions [8, 9]. This study design ws hosen to enble performne s lose s possible to the routine proess t the hospitl nd lso llow for omprtive nlysis with other routine experienes reported in the literture [11, 12]. Thus, in this prospetive study, ount inrement levels were used s mrkers of linil performne. CCI 1h, mrker of pltelet reovery, n be used s surrogte for pltelet qulity; hene, results showing rte of 65% effetive trnsfusions in multiple trnsfused ptients lie definitely within the expeted levels of response nd n onfirm dequte pltelet qulity. This level of suessful trnsfusions is slightly inferior to wht hs been reported by investigtors in the Netherlnds (72%), equl to wht hs been reently observed in Switzerlnd (65%) nd superior to the reports from Norwy (46%). In ll of these instnes, pltelets treted with n lterntive pthogen redution tehnology hd been used [10 12]. Moreover, the observed rte is slightly inferior to wht ws observed in the MIRACLE study fter trnsfusion of M-PC (71.3%) [13]. CCI 24h is mrker of survivl nd onsequently very dependent on ptient onditions. In view of the ft tht 68% of the ptients presented with pltelet onsumption ftors t the time of trnsfusion, suessful response rte of 42% is quite eptble. This ptient vrible beomes more evident if the linil responses by ptient group re nlyzed (fig. 2b). Besides, the response rte observed in the present study ws in the rnge observed in studies using lterntive tehnologies, whih rnge from 64% in the Duth, 53% in the Norwegin nd 28% in the Swiss reports. In the MIRACLE study, responses bove the CCI 24h threshold were observed in 51% of trnsfusions. With regrd to sfety, two mild llergi retions were reorded in 2 ptients tht were resolved without medition. These retions were onsidered possibly relted to the trnsfusion of the blood produt, implying rte of 1.5% for dverse events relted to trnsfusion. This rte is fr below the observed rte of 8% reported elsewhere for pthogen-intivted pltelet produts treted with n lterntive tehnology, nd onsistent with prior reports on M-PT [11, 14]. Altogether, the experiene quired in the proessing of M-PT under routine-like onditions nd used in the supportive tretment of thromboytopeni ptients showed tht the tehnology is esy to implement in the blood bnk routine nd tht the treted pltelet-ontining produts were sfe nd effetive. Aknowledgement The uthors wnt to thnk Mr Antoon for the support with the sttistil nlysis used to hek the librtion of the ell ounters. Dislosure Sttement Rhel Kilin nd Mri Crdoso re employees of Terumo BCT Europe. The other uthors hve no onflit of interest to dislose. 8 Trnsfus Med Hemother 2017;44:5 9 Vilriño/Cstrillo/Cmpos/Kilin/Villmyor/ Crdoso

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