1 / 43

Leukodepletion, Pathogen Inactivation, Irradiation – For some, or everyone?

Leukodepletion, Pathogen Inactivation, Irradiation – For some, or everyone?. Aleksandar Mijovic King’s College Hospital/National Health Service Blood & Transplant London, UK. Zadar 2011. Immunologic effects. Alloimmunisation Febrile non-haemolytic reactions Platelet refractoriness

ruby-lamb
Download Presentation

Leukodepletion, Pathogen Inactivation, Irradiation – For some, or everyone?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Leukodepletion, Pathogen Inactivation, Irradiation – For some, or everyone? Aleksandar Mijovic King’s College Hospital/National Health Service Blood & Transplant London, UK Zadar 2011

  2. Immunologic effects Alloimmunisation Febrile non-haemolytic reactions Platelet refractoriness Rejection of transplanted organ Graft-vs-host disease Immune modulation Increased risk of bacterial infection (?) Increased recurrence of malignancy (?) Infectious disease transmission CMV HTLV-I Epstein-Barr virus vCJD? Adverse effects of leukocytes in blood components Modified from: McCullough 2005

  3. vCJD • 4 cases in UK due to transfusion of non-leukodepleted red cells from donors who later developed vCJD. • Incubation period 6-8.5 years

  4. Infectivity of experimental TSE’s in blood -intracerebral route(Brown et al, Transfusion 1998:38;810)

  5. vCJD - What’s been done to prevent transmission? • Universal Leukodepletion (1999) • Import of plasma from USA • Donor selection – ban of donors who received transfusions after 1980 • Donor testing not yet available • Prion-reduction filters (for children and patients with haemoglobinopathies) – 2012?

  6. Universal Leucocyte Depletion -specification (UK SACBC)

  7. Effect of Leukodepletion on NH-FTRYazer et al, 2004; Pruss et al, 2004 NH-FTR rate [%]

  8. Effects of Leukodepletion on Platelet Refractoriness • TRAP study, 1997 • Lymphocytotoxic antibodies • 45% controls • 17-21% in treated groups • Platelet Refractoriness • 13% controls • 3-5% if platelets filtered or UV light-treated • After leukoreduction in Canada: • Alloimmunisation reduced from 19% to 7% • Immune refractoriness reduced from 14% to 4% • Seftel et al 2004

  9. Leukodepletion for cardiac surgery • Randomised study of: a) Buffy-coat depleted RBC; b) filtered, fresh RBC; c) filtered RBC, post storage • Infection rates: • 23.0% : 16.9% : 17.9% • Mortality: • 7.8 % vs 3.6% vs 3.3% Van de Watering et al 1998

  10. Leukodepletion in hospitalised patientsDzik W et al, Transfusion 2002 • 2780 pts randomised to receive LD or non-LD blood products. • No difference in primary outcomes: 1) In-hospital mortality; 2) Length of hospital stay (LOS); 3) Hospital costs • Nor in secondary outcomes: 1) LOS in ICU; 2) post-operative LOS; 3) antibiotic usage; 4) re-admission rate

  11. Risk for CMV disease in BMT(Ljungman et al 1998)

  12. PREVENTION OF CMV INFECTION • Use of CMV Neg Blood Products • Incidence ofCMV Infection reduced to 0-7% (pneumonia ~ 0%) • Leukodepletion • Equally effective to donor screening(Bowden et al 1995) • Abandonment of CMV screening premature(Nichols et al 2003)

  13. Leukodepletion vs CMV serology to prevent CMV infection • Both are effective • Neither is perfect • Not possible to decide if one is better than the other • Benefit of using both is unknown Canadian Consensus Conference 2001

  14. Pathogen Inactivation:in search of Zero-risk?

  15. SHOT report 2010

  16. SHOT report 2010

  17. Estimated risk of viral transmission by transfusion in the UK [per million donations](2009) www.hpa.org.uk

  18. 414 blood donors in 2005 340 blood donors in 2006 1500 clinical cases with 9 deaths 2006

  19. PATHOGEN INACTIVATION/REDUCTIONkey issues • 1. Effective inactivation of a range of agents; no evidence of toxicity. Compare with current alternatives. • 2. Underlying residual risk in a given country. • 3. ?Threat from new (or newly identified) microbial agents. • ?How to measure safety increment from PI. • Logistics; process control. Separate PI steps needed for each blood component • 6. ?Cost-benefit.

  20. HIV >6.2 HBV >5.5 HCV >4.5 CMV >5.9 West Nile >6.0 HTLV I/II 4.7-5.1 ParvoB19 4.0-4.9 E.Coli >6.4 S.Aureus 6.6 P.Aeruginosa 4.5 B.Cereus >6.0 Yersinia E. >5.9 P.Falciparum 7.0 T.Cruzi >5.3 Inactivation of Pathogens in platelets by S-59 (Log)

  21. Photochemical Treatment of Platelets – euroSPRITE trial • Randomised study (52 v 51 pts) of Amotosalen(S-59) treated BC platelets. • Average dose: 3.9 vs 4.3 x 1011 (p<.001) • 1-h increment: 27.5 vs 35.8 x 109 /L. Difference 8.3 (95% CI, 0.9 – 15.8) (p=.03) • 1-h CCI: 13.1 vs 14.9 x 103 (p=.11) • Bleeding/adverse events not different Van Rhenen et al 2003

  22. Photochemical Treatment of Platelets – SPRINT trial • Randomised study (318 v 327 pts) of Amotosalen(S-59) treated apheresis platelets. • Average dose: 3.7 vs 4.0 x 1011 (p<.001) • Grade 2 bleeding: 58.5% vs 57.5% (NInf) • Grade ¾ bleeding: 4.1% vs 6.1% (Ninf) • 1-h CCI: 11.1 vs 16.0 x 103 (p<.001) • Units received: 8.4 vs 6.2 (p<.001) McCullough et al 2004

  23. MIRASOL randomised trialMirasol Clinical Evaluation Group 2010 • Mirasol: Riboflavin (vitamin B2) + UV light • RCT: 56 pts (303 transf.) received PR-platelets, 54 pts (238 transf.) received reference platelets. • Primary outcome: 1-hour CCI • PR-P vs REF-P: 11725 : 16939 (criteria for non-INF not met). • PLT/RC utilisation not significantly different; Safety profile similar.

  24. Plasma - Spoiled for Choice? • Fresh Frozen Plasma • Solvent/Detergent treated plasma • Methylene Blue/UV light treated plasma

  25. FFP vs S/D vs MB Plasma: risk of disease transmission

  26. A.S., 18 y, TTP 22 Plasma exchanges Pulmonary Embolism R Fem Vascath L Fem Vascath Prednisolone = SD/Cryopoor plasma exchange

  27. COMPARATIVE STUDY OF TWO TYPES OF PLASMA IN LIVER TRANSPLANTATION RETROSPECTIVE, SINGLE CENTRE STUDY OF ADULT ORTHOTOPIC LIVER TRANSPLANT PATIENTS: 200 S/D FFP OCTAPLAS (1998-2001) 199 SINGLE DONOR FFP (after March 2001) ENDPOINTS PRIMARY: AMOUNT OF BLOOD PRODUCTS USED ESTIMATED BLOOD LOSS USE OF OTHER HAEMOSTATIC PRODUCTS SECONDARY 48HRS MORTALITY

  28. RESULTS

  29. S/D plasma or FFP ? Viral safety Reduced risk of TRALI Reduced risk of vCJD? Increased blood usage in OLT Increased VTE risk Cost

  30. Conclusions Use S/D PLASMA in: • Below age 16 • Young patient with good immediate and long-term prognosis, anticipated to receive few blood products. • Thrombotic Thrombocytopenic Purpura

  31. Transfusion related onset 2-30 days pancytopenia/BM aplasia No response to Th Mortality >90% Post BMT/PBPCT onset 35-70 days rare BM aplasia Incidence 20-70% 80-90% respond to Th mortality 10-15% Acute GVHD

  32. Graft-versus-host disease of the skin

  33. Transfusion-associated Graft-vs-Host disease: Prevention Gamma/ X-ray Irradiation 25Gy Leukodepletion – does it prevent TA-GVHD? - No case since 2001 in UK Pathogen Inactivation for Cellular Components

  34. Indications for irradiation of blood components in the UK A. Indication by patient condition • Intrauterine transfusions • Neonatal exchange transfusions • Congenital immune deficiencies • Allogeneic HSC transplant patients • Autologous HSC patients • Hodgkin’s disease • Purine analogue treatment • Aplastic anaemia treated with ATG or Alemtuzumab B. Indication by component type • Granulocyte transfusions • HLA-matched blood components • Blood components from relatives

  35. Frequency of Homozygous HLA donors to recipients heterozygous for the same haplotype[1 : x]

  36. Survey of Blood Use in France (1997)175 Hospitals, 3206 Transfused Patients 57% of transfusion recipients were > 65 years Mathoulin-Pelissier et al, Transfusion 40:1140, 2000

  37. “Greying” of the Population • Life Expectancy in UK (2001) • 80 y for Women • 75 y for Men • In 2007, people ≥ 60 were 21.8% of UK population. • The same year, people aged 65+ outnumbered those under 16 y for the first time ever. UN Dept. of Economic & Social Affairs

  38. Who should we irradiate blood products for? • According to national guidelines • All recipients with malignant disease • Recipients > age 65 yr • Everyone

More Related