1. The Decision!!! Gene Therapy or Bone Marrow Transplant? Emily Mullan Senior Staff Nurse Andrea Stephenson Practice Educator Great Ormond Street Hospital

2. Gene Therapy to Date 10 X-SCID 3 ADA Deficient SCID

3. Bone marrow/Cord/Stem Cell Transplants to Date The unit will approximately carryout 70 transplants per annum 35 of those will be for immunology conditions 9 of those were for children with SCID Data gathered from 2005/2006 (NSCAG)

4. Families Choice Matched family donor will always be first choice Due to the poor outcomes experienced for Mismatch or Matched Unrelated Donor for ADA SCID, current protocol is to offer Gene Therapy over a Matched Unrelated Donor for ADA SCID

5. Positive Aspects to Blood/Bone Marrow Transplant Increased knowledge in treatment Known short-term and long-term side effects Quicker immune reconstitution Increased knowledge in long-term prognosis Improve survival rates due to minimal intensity conditioning (Rao et al,1995)

6. Negative Aspects to Blood/Bone Marrow Cell Transplant Finding a donor, availability of Donor Multiple known long-term and short-term side effects Greater side effects due to intense conditioning regimes Extended neutropenic phase Extended inpatient stay leading to greater social isolation and less social skills (Vannatta et al, 1998 ) Psychosocial impact of longer separation time from siblings (Packman,1999, Sharpe and Rossiter, 2002)

7. Positive Aspects to Gene Therapy Not dependent on donor search Decreased short-term side effects due to milder conditioning. Shorter Neutropenic phase Shorter in patient stay leading to quicker family reconciliation Possibility of having a Blood/Bone Marrow Transplant if gene therapy unsuccessful

8. Negative Aspects to Gene Therapy Slower immune reconstition Unknown long-term side effects Limited experience due to pioneering stages of gene therapy Known side effects: previous gene therapy trial in Paris involving two X-SCID children developed monoclonal lymphoproliferative disease

9. Additional Considerations Fear, guilt and stress regarding initial diagnosis The unknown can be extremely stressful Decision may have to be made when the child is extremely unwell Hard to comprehend how fatal the condition If gene therapy is unsuccessful the child will have to be treated with a Blood/Bone Marrow Transplant, child will be older- link between between better psychological recovery the younger the child Parents have expressed anxieties due to one day they will have to explain the treatment choice

10. Additional Considerations Research identifies link between nutrition and long-term growth and development (O’connor, 2004). Gut complications seem to be reduced in Gene therapy Low conditioning regimes has improved outcome of BMT for child with an underlying immune problem (Rao et al 2005) Research has identified that parents don’t always feel supported the longer the illness continues ( Hoekstra- Weebers et al, 2001 ) Newcastle have had good results from their cord transplants for ADA SCID ADA SCID are know to have emotional/behaviour problems not thought to be connected to the transplant procedure (Rogers et al, 2001)