PGD & BMT – one family’s story

1. PGD & BMT – one family’s story Presentation and Q&A

2. Who we are and why we are here • Stuart & Natalie. Saskia, Alice, Imogen & George • Short presentation of our experiences • Opportunity for questions • Only us DBA HLA tissue match

3. The first four years • Diagnosed at 12 weeks • Transfusions • Steroids • Metaclopramide • Desferal • We decided on BMT

4. Pre-implementation Genetic Diagnosis (PGD) • Alice in a rush • PGD = IVF + ¼ Selection • In-vitro Fertilization (IVF) • Chicago – Chicago - London • 7 – 7 - 5 • Imogen

5. Bone marrow / stem cell transplant • Getting Worked Up and Wiggly • Sterile environment and Drugs, Drugs, Drugs • Day Zero • and counting • Lucky . . . • . . . but not easy . . . • . . . and 3 re-admissions

6. Post transplant • Wiggling on • Drugs, Drugs, Drugs • Patience and the out patient • Back to school • Jabs and backward transfusions • Long term • Q&A

7. Appendix: Overview of Saskia’s life with DBA August 2001 Saskia born 2001 onwards Monthly blood transfusions for Saskia from birth, though had a year-long break trying steroid treatment which failed. Also trialled another drug which failed. From age 3, nightly night-long infusions via needle of another drug to alleviate iron-overload problems. 2003 Second child born happy and healthy. Umbilical blood collected at birth. Blood discarded later when testing reveals this child is not a tissue match / potential donor for Saskia. 2004 Mum and Dad went to Chicago for IVF / PGD. Twice. Failed both times. 2004 Tried IVF / PGD in London when it became legal for us in the UK. Pregnant. 2005 Collected blood from umbilical cord at Imogen's birth and stem cells cryogenically stored. 2006-07 BMT work-up. Many tests to make sure Saskia is suitable and healthy enough for a transplant. March 2007 After Saskia became eligible for the transplant having passed many organ and blood tests, she had an operation (general anaesthetic) to have a Hickman Line inserted.

8. Appendix: Overview of Saskia’s life with DBA 25th March Saskia admitted to hospital and put into an isolation room. The room is kept at a pressure slightly higher than normal as clean air is pumped in continuously. People entering and leaving the room required to adhere to a strict protocol to minimise infection risk. Saskia given too many drugs to mention, the most notable of which are several "chemotherapy" drugs, the purpose of which is to kill off Saskia's bone marrow. The principal function of bone marrow is to make red blood cells (used to transport oxygen round the body), white blood cells (used to fight infections) and platelets (used to help the blood clot). 4th April Known as "Day Zero". The transplant day. Imogen has operation to take out some of her bone morrow (this grows back very quickly afterwards). This, together with the stem cells collected from the umbilical cord when Imogen was born in 2005, is given intravenously to Saskia. This is not an "operation" as such but a procedure similar in routine to the 50 or so blood transfusions she has had to date. For the next few weeks loads more drugs, seemingly 24 hours by Hickman Line, nasal tube and orally. Drugs to combat the side effects of drugs. Drugs to combat the side effects of those drugs. And again. No joke. Saskia has side effects, the most obvious being all her hair falling out, being sick lots and feeling very sick. During the time since admission a family member was in the room with Saskia 24-hours a day. 2.5 weeks later . . . Tests of Saskia's neutrophil count indicate that she may be starting to get the emergence of a new, though very weak immune system. Start taking short trips outside the hospital to big open spaces since Saskia is doing so well. Moved out of big isolation room to a smaller one getting ready for going home. A few days later . . . Overnight home visit (we live a short walk from the hospital, so very handy). Same the next night.

9. Appendix: Overview of Saskia’s life with DBA And in Late April . . . • Saskia is Discharged from hospital! We're told this is unusually soon after admission and that Saskia appears to have done really so far. Not able to tell what's going on in her bone marrow yet. It's too early to tell how successful the process has been in killing off her old bone marrow or whether the new bone marrow is producing red blood cells or platelets. • On 5 drugs, which is a relatively low number at this early post-discharge stage. Their purpose is: to help prevent infection by bacteria, viruses and fungi; to help prevent graft-v-host disease; and to reduce blood pressure. Getting Saskia to take these medicines is a real challenge. • Still severely immuno-deficient and at risk to infection. • Attending hospital 2-3 times a week for blood tests, check-ups and blood transfusions. • Saskia able to see friends one-on-one, and allowed to go out to wide open spaces or places with few people. • Saskia back to a less controlled diet, though some restrictions still in place. • Needs to wear sun-block outside since the process has left her skin very sensitive to the sun • Any infection could easily put her back in hospital, and we're told to "expect" readmission some time in the next 12 months for some setback or other. • Saskia is bald and beautiful.

10. Appendix: Overview of Saskia’s life with DBA Early/mid May After going in for a routine blood transfusion, Saskia is readmitted (first time) for observation and an extra intravenous antibiotic. She seems OK on whole but has been prone to occasional severe shivers which may indicate infection. Neutrophil count still going up. Platelet count seems holding at an encouraging level, but early days. Another blood transfusion. Certainly not making many red blood cells at the moment, which after all is the whole point. Stops taking the drug which controls blood pressure. She is discharged after 2 nights. No infections detected during this second stay in hospital, but doctors still extra wary. Saskia still has that cough. No shivers for a past few days. Late May Saskia seems very well. She is at home but visiting the hospital 2-3 times a week. She has met up with a few friends for one-on-one play dates. Her home schooling has started: 5 hours a week is not a lot but hopefully it will keep her up to speed with her peers. There have been some minor discipline issues as would be expected from a child who, for a few months, has been spoilt for attention, been highly controlled but had no routine. The daily grind to take the many medicines is getting slightly easier but still a challenge. Later May Results of first "chimerism" test come back to reveal how much Saskia's old bone marrow (which we hope to have killed) is still working and how much her new bone marrow is working. The test says that the bone marrow at work is at least 97% Imogen's - the test doesn't go higher than 97%. Saskia is taking her medicines better although we are having difficulty maintaining her cyclosporin levels (that's the one that protects against Graft Vs Host Disease). We still go in to hospital 2 - 3 times a week. No more blood transfusions. Hope to see first evidence of red cell production soon.