ALBERT

Description: This retrospective study looked at all patients with Haemophilia A who attended Manchester Pendlebury Childrens Hospital for their first and subsequent Factor replacement therapy between January 1980 and May 2005. The aim was to determine :- Does an increased number of different products used influence inhibitor formation. Does using a B domain deleted factor (Refacto) concentrate influence inhibitor formation. Does changing from plasma derived to recombinant factor influence inhibitor formation. A total of 107 patients who received a cumulative total of 65,102 trearment days were identified and the following information was recorded for each patient :-severity of haemophilia (mild, moderate or severe) and baseline factor VIII level, date and age of first product, all types of products used, number of treatment days used of each product, detection of inhibitor and if present date of ocurrence and age of patient. The policy of the unit was to test for inhibitors every six months, pre operatively or when clinically indicated. Thirteen different products were in use during the period of the study :- AHFC(anti haemophilic factor concentrate), Cryoprecipitate, 8Y, 8SM, Alphanate, Replenate, Monoclate P, Helixate, Refacto, Recombinate, Hemophil M, Advate and Haemate P. Only 4 patients out of 107 developed inhibitors and all were exposed to less than 4 products. Inhibitor patient demographics Haemophilia type and baseline factor VIII Number of treatment days before inhibitor Products used with respective treatment days Severe (

Description: Mucopolysaccharidosis type I (MPS-I [Hurler’s syndrome]) is an autosomal recessive condition caused by a deficiency of alpha-L-iduronidase. We report single centre 20 year experience of outcomes of BMT in MPS-IH. As there is no consensus about graft monitoring and the indication for second transplant, we describe the monitoring of graft function, indications for and management of second BMT in this institution. Data was collected from 43 patients receiving 61 transplants who underwent allogeneic transplantation at the Royal Manchester Children’s Hospital between 1985 and 2005. The median age at first transplant was 15 months (range 7– 44), and of these 23 were male and 20 were female. 24 of the first transplants were from an unrelated donor. Graft function was monitored prospectively in each transplant using enzyme levels, urinary GAGs and, for the last 33 transplants, VNTR analysis. Almost half of the 61 transplants carried out since 1985 have been done in the last five years. Of the 43 patients transplanted, 19 survived with stable engraftment, 16 patients rejected their first grafts and all 16 of these patients went on to receive a second transplant. GVHD occurred in 16 of 28 patients who received only 1 transplant. Of the 16 who had 2 procedures, 6 had GVHD after their first transplant and 8 after their second. 8 patients died and all deaths were due to transplant-related complications (1 EBV/LPD, 1 CMV, 4 Adenovirus, 2 GVHD). 24 patients received unrelated donor grafts. 16 of these MUD transplants were carried out before 2002 and 8 since 2002. 6 of the 8 deaths were in patients who received unrelated donor grafts and all 6 of these were pre 2002. This improvement in mortality is significant (Fisher’s exact test 2-sided p= 0.04). 45 of the 61 transplants were carried out after 1995 and these patients all had regular VNTR monitoring of their graft function. From these results 4 groups of graft status are identified: full engraftment, stable mixed chimerism, immediate rejection, early autologous reconstitution. 23 patients remain fully engrafted at 100% VNTR levels. 16 of these were after first transplant and 7 following their second transplant. 4 patients have stable mixed chimerism (2 after 1st transplant and 2 after 2nd). Although the VNTR levels are now not 100% in this group, they remained at 100% until at least 70 days post transplant. They reached a state of stable mixed chimerism at a mean of 203 days post transplant (range 133–280). The final level of mixed chimerism reached was a mean of 59% donor. 3 patients immediately rejected their graft with VNTR levels falling to 0% within 28 days of transplantation. 8 patients had early autologous reconstitution requiring a second transplant procedure once their VNTR levels fell to 20%, and in these there was early mixed chimerism (within 60 days after graft). All 16 patients who rejected their first graft went on to have a second transplant when their VNTR levels fell to