Transplants. Mickey B. C. Koh

Transcription

1 Transfusion in Stem Cell Transplants Mickey B. C. Koh Director: Stem Cell Transplant Programme Department of Haematology, St. George s Hospital and Medical School, London, UK Medical Director: Cell Therapy Facility Blood Services Group, Health Sciences Authority, Singapore Mickey.koh@stgeorges.nhs.uk; mickey_koh@hsa.gov.sg koh@hsa.gov.sg

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3 RBC TRANSFUSION GUIDELINES There is no fixed transfusion trigger When Hb >10g/dL - very littlel indication i for red cell transfusion When Hb <7g/dL - red cells transfusion probably beneficial but not always required When Hb is between 7-10g/dL - transfusion guided by the clinical signs and symptoms, coexisting medical problems and other risk factors (e.g. cardiovascular disease, respiratory disease etc)

4 Current Topics 1. CMV 2. Irradiation 3. ABO mismatched and blood support 4. Poorer outcomes with ABO incompatibility 5. Aplastic anaemia transplants and rejection 6. Hep E 7. Dengue and renal transplants 8. Tranexamic acid; norethisterone t

5 CMV 1. CMV negative products to CMV negative patient /recipient pairs 2. Can universal leucodepletion eliminate the need for CMV? 3. Most studies say yes if leucodepletion is less than 1-5x 10e6 remaining leucocytes 4. BSBMT and NHSBT guidelines: no need to select for CMV negative products 5. Currently reviewing practices in UK transplant centres and also to detect any cases of CMV transmission

6 CLINICAL EFFECTS OF CONTAMINATING LEUCOCYTES HLA Alloimmunisation Reactions Platelet Graft Refractoriness Rejection Viral Transmission i Cytomegalovirus (CMV) EBV, HTLV I & II, Varicella zoster Contaminating Leucocytes Immune Suppression Post Cancer Latent Operative Recurrence Viral Infection Reactivation

7 Irradiated Products 1. Irradiation: how long? 2. Allogeneic: consensus is lifelong but body of evidence not very strong 3. Initial evidence from Transfusion related GvHD 4. Decreasing Total Body Irradiation in Transplantation conditioning. 5. Autologous: How Long. 6 months-lifelong 6. Parallel situation to live vaccines

8 ABO mismatching 1. Major and minor mismatching 2. Previously: immune mediated haemolysis and perhaps suppression of engraftment including pure red cell aplasia 3. Transfusion support required

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10 ABO mismatching and survival 1. Controversial relationship with outcomes in Stem cell transplantation 2.?Poorer outcomes: Overall Survival and disease free survival 3.?GvHD 4. Ringden and Lungman: BBMT 2014 suggests an impact 5. Blin et al (BBMT 2010): no impact 6. Insufficient i data and so many other variables more critical in success of transplants

11 Aplastic Anaemia transplants 1. Higher incidence of graft rejection 2. Judicious use of blood products and alloimmunisation 3. Single donor apheresis platelets and leucoreduced products

12 Hepatitis E 1. Increasing incidence including increased teating and awareness 2. HEV most common acute enterically transmitted viral hepatitis in UK 3. Hewitt ittp et al l(lancet t2014) 2014): Review of fse England. Triggered by symptomatic cases 4. 2 patients post allogeneic stem cell transplant: acute rise ALT >1200.?GvHD vs hepatitis 5. Provision of Hep E negative products: changes in practice from cross-talk

13 Dengue and other pathogens 1. Renal transplant: reported in Singapore 2. Screening of transplant donors for potential infectious agents 3. Toxoplasmosis. West Nile

14 Blood Sparing Agents 1. Tranexamic acid: for clinical bleeding except for uro-genital. Example is BK viraemia post transplant with torrential haematuria 2. Norethiserone to stop menses 3. Treatment of Veno-occlusive disease with Defibrotide. Single Stranded phosphodiester but mechanism of action not fully eluccidated 4. Anti-thrombotic/anti-fibrinolytic thrombotic/anti fibrinolytic.?blood product support 5. Mucositis

15 Platelet transfusion threshold for BM failure patients Handbook of Transfusion Medicine. DBL Mc Clelland. 4 th edition

16 Lowering Platelet Thresholds 1. Can we lower platelet thresholds? 2. Can we move from prophylactic to therapeutic ti strategy? t 3. Stanworth NEJM: TOPPS trial. Prophylaxis still important. 7% reduction in bleeding although still occurs 4. STOP and PLADO trial

17 Definitions of Platelet Different Definitions: iti Refractoriness - 1-hour and/or 24-hour post-transfusion plt increment < 10 K OR 1 hour Increment < 5,000-7,500 OR Less than predicted platelet increment on 2 occasions within 24 hours of Transfusion (< 2K increment in plt count per unit of PLC given) with: Fresh platelets: < 72 hours. ABO compatible. OR Corrected Count Increment: (Platelet increment X BSA)/Platelet dose Expected > 7500 at minutes or >4500 at hours.

18 PLATELET SUPPORT FOR REFRACTORY PATIENTS Exclude other causes of platelet destruction Fever Sepsis / Infection Splenomegaly l DIC Drugs (vancomycin, amphotericin, i heparin, etc.) GvHD Micro-angiopathic anaemias

19 AABB Tech Manual Blood and Marrow-Derived Non-Hematopoietic i Stem Cell Sources and Immune Cells for Clinical Applications Mickey B C, Koh,, Edward R Samuel,, and Garnet Suck, Mesenchymal Stromal Cells

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21 Transfusion, Blood Services and Transplants 1. Transfusion is a form of cell therapy 2. Cell therapy and new products for cancer and regenerative medicine 3. Platelet lysates and new generation of products 4. Blood banking and leucopheresis

22 Management plan for patients who refuse transfusion of blood and blood products

23 Thank You