Pathogeninaktivierte vs konventionelle Thrombozytenkonzentrate, Daten einer retrospektiven Hämovigilanzstudie. Volker Witt (Wien/AT)

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1 Pathogeninaktivierte vs konventionelle Thrombozytenkonzentrate, Daten einer retrospektiven Hämovigilanzstudie Volker Witt (Wien/AT)

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3 INTERCEPT in pediatric patients Benoit Y. ; Blood 2004, 46th ASH meeting, 2004 interim report 158 transfusions 21 patients Age 1 16 year Comparable rate of adverse events Comparable rate of disruption of bleeding Comparable rate of CCI (corrected counted increment)

4 Study design Prospective and observational single-arm open label retrospectively compared to non Intercept platelet concentrates

5 Study design from to Observational study 998 transfusions of platelet concetrates (PC) in 150 patients evaluable 952 transfusion episodes 317 transfusions of pathogen inactivated PC 635 transfusions of non pathogen inactivated PC Transfusions per patient Intercept in median 2 PC (range 1 23) non Intercept in median 3 PC (range 1 48) Median age at transfusion was 11.6 years (range years)

6 Study design Indications for PC s have been retained unchanged All PC were irradiated and leukodepleted Pathogen inactivated PC s were producd on 2 days a week One PC transfusion episode was the trasnfusion of one PC in one patient Every patient could recieve Intercept or non Intercept PC s If no pathogen inactivated PC was available a non Intercept PC was ordered and transfused informed consent of the ethical committee

7 Study design Parameter Blood smear at time of indication 1h after transfusion of the PC Or before the next transfusion of a PC if necessary Calculation of the Corrected counted increment (CCI) Bleeding score before and after the trasnfsuion performed by the responsible physician

8 Study design We retrospectively compared episodes from Intercept PC s with episodes from non Intercept PC s We used descriptive statistics, U-test, T-Test, Mc Nemar test, p < 0.05 was accepted as significant Absolute increase of platelets in peripheral blood after transfusion CCI Frequency of adverse events Bleedingscore before and after

9 Study design thrombocytopenia < 10G/l Bleeding and thrombocytopenia < G/l > 4 months < 18 years Pathogen inactivated (Intercept ) PC non pathogen inactivated (Intercept ) PC

10 Study design Transfusion 1 h Wert (komplettes Blutbild) Blutungsscore Transfusionsbericht über die Gabe eines Thrombozytenkonzentrates nein UAW ja Transfusionsbericht über die Gabe eines Thrombozytenkonzentrates + Transfusionsbericht über UAW Dokumentation abschließen und in INTERCEPT Kasten geben

11 Blutungs-Grading bei pädiatrischen Patienten (vereinfacht nach Buchanan et al.: J Pediatr 2002;141: ) I. allgemeine Blutungsneigung (overall bleeding severity) 0 (keine), 1 (minimale), 2 (milde), 3 (mittelgradige), 4 (schwere/starke), 5 (lebensbedrohliche Blutungsneigung) 1: <100 Petechien und/oder < 5 kleine (< 3 cm) blaue Flecken, keine SH-Blutungen 2: >100 Petechien und/oder > 5 große (> 3 cm) blaue Flecken, keine SH-Blutungen 3: SH-Blutungen (auch Menorrhagien, GI-Blutungen) ohne Notwendigkeit einer medizinischen Intervention 4: SH-Blutungen (auch Menorrhagien, GI-Blutungen) mit Notwendigkeit einer medizinischen Intervention 5: Lebensbedrohliche/tödliche Blutung

12 results Relative Häufigkeit (%) 45,00 40,00 35,00 30,00 25,00 20,00 15,00 10,00 5,00 0,00 0 bis 5 5 bis bis 15 > 15 Alter ICB J=1 N=0 0 1

13 results Relative Häufigkeit (%) 60,00 50,00 40,00 30,00 20,00 10,00 ICB J=1 N= , Codierung Diagnose 1 = hematological malignancies, 2 = solid tumours, 3 = after stem cell transplantation (autologous or allogeniec)

14 results Relative Häufigkeit (%) 90,00 80,00 70,00 60,00 50,00 40,00 30,00 20,00 10,00 0,00 allogen autolog mibg nach autologer/allogener PBSCT ICB J=1 N=0 0 1 ICB 0 n = 70; ICB 1 n = 29

15 results ± Standardabw eichung plt Wert vor Transfusion G/l 90,00 80,00 70,00 60,00 50,00 40,00 30,00 20,00 10,00 0, ICB J=1 N=0

16 results ± Standardabw eichung plt Wert nach Transfusion G/l ICB J=1 N=0

17 results 50 p < ; U-Test (Mann-Whitney) CCI (G/l) ,91 ± 0 10,41 8,43 1 ± 8,37 Non Intercept Intercept ICB J=1 N=0

18 results Thrombozyten-gehalt der Konserve (Tx10^11) 4,00 3,50 3,00 2,50 2,00 1,50 1,00 0,50 0,00 p = 0.69; T-Test 0 1 ICB J=1 N=0 Content of platelets of the platelet concentrates [Tx10^11]

19 results Storage time was comparable between Intercept and non Intercept PC s before transfusion Intercept (n=143) 2.31 ± 0.07 days Non Intercept (n=298) 2.39 ± 0.06 days p = 0.408; T-Test

20 results Bleeding score ICB 0 ICB 1 pre post pre post

21 results Reduction of the bleeding rate in the non Intercept group from 53 to 24 episodes (= 55%) and in the Intercept group from 38 episodes to 15 episodes (= 61%) After transfusion no life threatening bleeding was in neither group observed. In the whole study population no death occured due to an PC transfusion or due to bleedings or their complications.

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24 ROTEM non Intercept PC Thrombo 22 G/l Thrombo 100 G/l

25 ROTEM Intercept PC Thrombo 19 G/l Thrombo 36 G/l

26 results: adverse events Non Intercept Intercept Summen UNW Ja UNW Nein Summen Chi-Quadrat Freiheitsgrade P Kappa 614, ,

27 conclusion In our pilot study even with irradiated Intercept products, Intercept PC s were well tolerated in children and young adults Less adverse events were observed compared to conventional PC transfusions Bleedings were controlled sufficiently by Intercept PC comparable with non Intercept PC transfusions In vitro tests with ROTEM showed aquivalent results for Intercept and conventional PC s

28 McCullough J. Blood 2004;104: (SPRINT Trial)

29 Snyder E. Transfusion 2005;45: (SPRINT Trial)

30 ISBT Cape Town 2006 P-369 Therapeutic efficacy and safety of transfusion of pathogen-inactivated platelets to pediatric patients L.van Haute, et.al. Gent, Belgium, Vox Sanguinis (2006) 91 (Suppl 3) INTERCEPT system Baxter Healtcare Inc. 471 transfusion episodes 90 pediatric patients 51% leukemia 34% solid tumor 4 % aplastic anemia 11% others Corrected Counted Increment (CCI) adverse reactions < 24h

31 ISBT Cape Town 2006 P-369 Therapeutic efficacy and safety of transfusion of pathogen-inactivated platelets to pediatric patients L.van Haute, et.al. Gent, Belgium, Vox Sanguinis (2006) 91 (Suppl 3) transfusion episodes / patient median 6 (1-49) number of platelets transfused / transfusion episode median 3,1 x 1011 (1,7 4,2) CCI / transfusion episode mean 12,257 (SD 8,905) CCI / patient mean 14,822 (SD 7,602) 11 (2,3%) transfusion reactions in 10 (11%) patients 8 fever, 1 urticaria and rash, 2 vomiting

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34 Pathogen inactivated and conventional platelet concentrates in children, young adults and adolescents, a retrospective time series cohort study on the hemovigilance Volker Witt (Wien/AT) PRS V10

35 study design The time series, or before-after study is a variation of a cohort study. The investigator takes a measurment of interest, exposes the trial population to an intervention, and repeats the measurement of interest. Limitations of such studies include the possibility of carryover effects of the intervention, regression to the mean for extreme measurements, and disregard for secular trends. Tay J, Tinmouth A. Transfusion 2007;47:

36 Patient population Introduction of PI TC study design March 2012 Conventional PC = PC Pathogeninactiveted PC = IC Patient recieves conventional PC only Patient recieves pathogeninactivated PC only Patient recieves conventional an pathogeninactivated PC Tay J, Tinmouth A. Transfusion 2007;47:

37 sex n = m f

38 Patients characteristics 174 male 121 female at first transfusion Median age 7.54 y ( y) n= % < 1 y y > 18 y 24 8

39 How long stayed the patient under observation in median 92 days (min/max days) n= days in study

40 underlying disease ALL/Lymphoma solid tumor non malignant disease AML BM disease 28

41 transfused platelet concentrates n= PC PC in additive solution 198 PC washed IC IC washed 65

42 reactions y/n frequency (n=) n= n 64 reaction no / yes y ) PC; 2) PC in additive solution; 3) PC washed; 4) IC; 5) IC washed

43 reactions y/n percentage 120,00 100,00 97,73 97,36 98,48 99,42 98, ,00 2 (%) 60, , ,00 0,00 n 2,27 reaction no / yes 2,64 1,52 y 0,58 1,54 5 1) PC; 2) PC in additive solution; 3) PC washed; 4) IC; 5) IC washed

44 H-Test (Kruskal-Wallis) product type N reaction y/n median rank PC , PC in additive solution , PC washed , IC , IC washed , H degrees of freedom P 27, ,85916E-05

45 number of patients transfused PC IC PC reaction IC reaction non malignant disease under chemotherapy after allo SCTx after auto SCTx Total

46 number platelet concentrates transfused PC IC PC reaction IC reaction non malignant disease under chemotherapy after allo SCTx after auto SCTx Total

47 Patients with non-malignant diseases transfused PC IC reaction y reaction n CHI² p = 0.36

48 Patients with non-malignant diseases transfused PC 15 0 PC and IC 13 IC

49 Platelet concentrates in non-malignant diseases number of transfusion episodes PC IC reaction y reaction n CHI² p = 0.23

50 Patient under chemotherapy transfused PC IC reaction y reaction n CHI² p < 0.009*

51 Patient under chemotherapy transfused PC PC and IC IC

52 Platelet concentrates in patient under chemotherapy number of transfusion episodes PC IC reaction y reaction n CHI² p < 0.001*

53 Patient under/after allogeneic stem cell transplantation transfused PC IC reaction y reaction n CHI² p = *

54 Patient under/after allogeneic stem cell transplantation transfused PC 25 9 PC and IC IC 32

55 Platelet concentrates in patient under/after allogeneic stem cell transplantation number of transfusion episodes PC reaction y reaction n IC CHI² p < *

56 Patient under/after autologous stem cell transplantation transfused PC IC reaction y reaction n CHI² p = 1.0

57 Patient under/after autologous stem cell transplantation transfused PC 15 1 PC and IC IC 9

58 Platelet concentrates in patient under/after autologous stem cell transplantation number of transfusion episodes PC IC reaction y reaction n CHI² p = 1.0

59 Type of adverse events n= allergic anaphylactic febrile 1) PC; 2) PC in additive solution; 3) PC washed; 4) IC; 5) IC washed

60 severity of adverse events n= light severe 1) PC; 2) PC in additive solution; 3) PC washed; 4) IC; 5) IC washed

61 severity of adverse events (%) 70,00 60,00 50,00 40,00 30,00 20,00 10,00 0, light severe 1) PC; 2) PC in additive solution; 3) PC washed; 4) IC; 5) IC washed

62 Witt et al. DGTI Düsseldorf 2009 Van Haut et al. ISBT 2007 Osselaer et al. Vox Sanguinis (2008)94, Osselaer et al. TRANSFUSION 2008 doi: /j x. Rasongles et al TRANSFUSION 2008 doi: /j x

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66 conclusion Intercept treated platelet concentrates have less side effects than conventional platelet concentrates Side effects are less severe in Intercept PC High risk groups like pediatric patients under conventional chemotherapy and after allogeneic stem cell transplantation showed in our analysis the best profit