Transplantation To infinity and beyond July 2018 Dr Bill Monday - PowerPoint PPT Presentation

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Transplantation – To infinity and beyond July 2018 Dr Bill Monday Pacific Life Re

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL — Overview — Topics covered in this presentation 01 Overview of transplantation in Australia 02 Solid organ transplantation 03Stem cell transplantation 04 Bio-printing Pacific Life Re

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL — Overview — Aim of talk: 1.To make you all organ donors ☺ …. ( https://register.donatelife.gov.au/decide) 2.To get a feel for transplants in Australia 3.To note use of stem cell transplantation in MS 4.To ensure you don’t change your home printer into a bio - printer yet….. Pacific Life Re

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Transplantation Pacific Life Re

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL - Section 01 - Overview of transplantation in Australia Pacific Life Re

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Transplants performed in Australia from deceased donors. http://www.anzdata.org.au/anzod/updates/20180606_ANZODMonthlyReport_2018May.pdf Pacific Life Re 6

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Transplants performed in Australia from deceased donors. http://www.anzdata.org.au/brochures/brochure_2016v1.0_20180417.pdf Pacific Life Re 7

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Transplants performed in Australia from deceased donors. Multi-organ Jan – May Jan May- 2018 Number of transplants Transplant 2017 Kidney 385 Heart and lungs 3 Liver 127 Kidney and Heart 4 Heart 57 Kidney and Liver 5 Lung 184 Kidney and Lungs 1 Pancreas 18 Kidney and Pancreas 16 Stomach and intestine 0 Total 29 http://www.anzdata.org.au/anzod/updates/20180606_ANZODMonthlyReport_2018May.pdf Pacific Life Re 8

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Survival of Graft 1997-2016 http://www.anzdata.org.au/brochures/brochure_2016v1.0_20180417.pdf Pacific Life Re

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Pacific Life Re 10

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Solid Organ Survival Australia 1 Year 5 Year 10 Year Kidney 99-97% 96-90% 83-74 Heart 87% 81% 70% Lung 93% 70% 32%* Pancreas 96% 92% 82% * USA survival data Pacific Life Re 11

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Common causes of renal disease leading to renal transplant. Diabetes- 31% • Chronic Glomerulonephritis 28% • Polycystic Kidney Disease-12% • Nephrosclerosis 9% • Lupus 3% • Interstitial Nephritis 3% • Other 14% • Pacific Life Re 12

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Outcomes after transplants Standardised mortality per 100 patient years: Dialysis 6.3 • Cadaveric transplant 3.8 • Living Donor transplant 2.0 • Pacific Life Re

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Causes of death in renal transplant patients tp://www.anzdata.org.au/anzdata/AnzdataReport/40thReport/chapter03_mortality_2016_v1.0_20180411.pdfht Pacific Life Re 14

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Long term complications of transplantation Cardiovascular disease (Death With a Functioning Graft- DWFG) 7.6% chance of MI or • coronary revascularization after 5 years. Why? • More calcification in arteries • More LVH. • Caution esp in- • Diabetics, • CVS disease during dialysis • Ongoing proteinuria. • Renal function post transplant also NB with a 16% increase in CVS events for every • 5ml/min/1.73m 2 decrease below a eGFR of 45ml/min/1.73m 2 Immunosuppression including steroids increase BP and increase dyslipidaemia. • https://academic.oup.com/bmb/article/106/1/117/322190. Update on long term Pacific Life Re 15 complications of renal transplantation Mathew J Bottomley et at British Medical Bulletin 02 May 2013

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Long term complications of transplantation Cancer (DWFG) • Cardiovascular disease and cancer account for 47% of all deaths with a functioning • graft with 27% of death being due to cancer) Majority of cancers are Non Melanoma Skin Cancers (NMSC) • Lymphomas higher than the general population • Kaposi’s Sarcoma more common in transplanted patients • https://academic.oup.com/bmb/article/106/1/117/322190. Update on long term Pacific Life Re 16 complications of renal transplantation Mathew J Bottomley et at British Medical Bulletin 02 May 2013

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Long term complications of transplantation- Cancer https://academic.oup.com/bmb/article/106/1/117/322190. Update on long term Pacific Life Re 17 complications of renal transplantation Mathew J Bottomley et at British Medical Bulletin 02 May 2013

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Immunosuppresssion All kidney transplants require life long immunosuppression to prevent T cell rejection. It’s • a bit of a balance as you need to: Prevent acute and chronic rejection. • Minimize drug toxicity and rates of infection and malignancy • Complications include: Rejection • Nephrotoxicity of certain immunosuppressive drugs such as Cyclosporin and Tacrolimus • Recurrence of native kidney disease • Acute rejection occurs in first 6 months (15% of cases) • Chronic rejection occurs more than a year after transplantation • Pacific Life Re 18

FOR INTERNAL USE ONLY / PRIVATE & CONFIDENTIAL Complications of common Transplant drugs Complications CVS Carcinogenesis Other Nephrotoxicity Ciclosporin ↑BP, ↑ Lipids, Yes, carcinogenic Pancreatitis, All transplants have ↑ Diabetes risk impaired function ( even if biochemically Tacrolimus ↑BP, ↑ Lipids, No carcinogenesis Insomnia normal) . To avoid ↑ Diabetes risk Headaches any medication that may effect the Azathioprine No effect Yes, carcinogenic Low White cell kidney such as count NSAIDs, Certain antibiotics such as Mycophenolate ↑ Lipids Possible, some Teratogenic evidence Aminoglycosides Sirolimus ↑ Lipids Possible, some Pneumonititis, evidence oedema Everolimus ↑ Lipids Possible, some Pneumonititis, evidence oedema Corticosteroids ↑BP, ↑ Lipids, Limited evidence ↑ Diabetes risk Pacific Life Re 19

FOR INTERNAL USE ONLY / PRIVATE & CONFIDENTIAL Underwriting considerations of transplanted patient- Kidney. Deceased or living donor in case of kidney Present renal function- preferably eGFR, Creat below 150 as rule of thumb Presence of proteinuria , hypertension Cardiovascular, cancer and diabetic risk Medication and side – effects of medication. https://academic.oup.com/bmb/article/106/1/117/322190. Update on long term complications of renal transplantation Mathew J Bottomley et at British Medical Bulletin Pacific Life Re 20 02 May 2013

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Pacific Life Re 21

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL - Section 03 - Stem Cell Transplantation. Pacific Life Re

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Stem cell transplants – Around a 1000/year in Australia Indications: • Leukaemia • Lymphoma • Myeloma • Amyloidosis • Aplastic anaemia • Some solid tumours (e.g testicular cancer, breast cancer) • Some immune system disorders (scleroderma) • MS Pacific Life Re 23

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Stem Cell Transplant. A stem cell transplant replaces blood forming cells in your bone marrow that have been destroyed by chemotherapy or radiotherapy with healthy stem cells A stem cell transplant can be your own stem cells ( Autologous 2/3 of cases ) or stem cells from a donor ( Allogenic) Stem cell transplants have 4 main phases 1)Stem cell collection from you or a donor (1-2 weeks) 2)Transplant treatment (Chemotherapy or radiotherapy – 1 week) 3) IV transfusion of healthy Stem cells (1 day) 4) Recovery 2-12 weeks Pacific Life Re 24

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Survival after Stem cell transplant Survival improving due to better tissue matching, better supportive care and earlier referral for transplantation. Allogenic bone marrow transplants potentially curative with most deaths occurring in the first 2 years post transplant. 5 Year survival 89% and 10 year survival 85%. Causes of death- – Age related – Relapse of malignancy – Chronic Graft Versus Host Disease ( GVHD) – Second cancers ( 2-10% of deaths in late survivors) Australia at the forefront creating blood stem cells in the lab. Used pluripotent stem cells to create blood cells Pacific Life Re 25

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Graft Vs Host Disease This can only occur in Allogenic transplants The donated bone marrow/stem cells see the recipient’s body as foreign and attack, Graft vs Host disease can be acute or chronic GVHD can affect the skin, liver, eyes, mouth, lungs, GIT tract, neuromuscular system or genitourinary system. Immunosuppressives are prescribed thus increasing infection risk. Pacific Life Re 26

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL Fairly predictable and favourable prognosis after 2 years of survival Pacific Life Re 27 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107742/

FOR INTERNAL USE ONLY | PRIVATE & CONFIDENTIAL - Section 02 - Stem cell Transplantation in MS Pacific Life Re