B-cell depletion abrogates immune mediated cytopenia and rejection of cord blood transplantation in Hurler syndrome.

Umbilical cord blood is the preferred donor cell source for children with Inherited Metabolic disorders undergoing Hematopoietic Cell Transplant (HCT), and its use has been associated with improved "engrafted survival" and higher donor chimerism compared to other cell sources. However, as in other pediatric cord blood transplants for non-malignant disease, immune-mediated cytopenia and primary graft failure limit its use, and the latter remains the commonest cause of death following cord blood transplant for non-malignant disease. We have previously shown an association between immune-mediated cytopenia and graft failure in inherited metabolic diseases suggesting that both immune-mediated cytopenia and graft failure could be mediated by antibodies from the residual recipient B cells. Since rituximab is effective in depletion of B cells and management of refractory immune-mediated cytopenia following HCT, we have added rituximab to the conditioning regimen. We studied 57 patients in 2 centers who received myeloablative conditioning for cord blood transplant in Hurler syndrome, and report a significant improvement in event-free survival with reduced incidence of graft failure and without any evidence of immune-mediated cytopenia in those patients that had received rituximab.

Ritual circumcision: no longer a problem for health services in the British Isles.

INTRODUCTION: Primary care trust (PCT) funding of a ritual circumcision service has recently been withdrawn from our unit, raising concerns that this may result in greater morbidity from community circumcision. The aims of this study were to document our circumcision practice before and after the withdrawal of PCT funding and to determine its effect on the morbidity from circumcision. In addition, we wanted to survey all paediatric surgical centres in the British Isles to ascertain how many still offer a ritual circumcision service. PATIENTS AND METHODS: We retrospectively reviewed our circumcision practice for 1 year prior to the removal of UK Government funding, and then performed a prospective audit of our practice for the 12 months following funding withdrawal. An e-mail survey was also performed of all paediatric surgical units to determine the ritual circumcision service provision throughout the British Isles. RESULTS: A total of 213 boys underwent circumcision during the 12 months prior to the withdrawal of funding, of which 106 cases (50%) were ritual circumcisions. After funding withdrawal, 99 boys underwent circumcision, of which 98 cases (99%) were for medical reasons. A similar number of boys were re-admitted after a hospital circumcision during the two review periods (5 versus 4 patients), whereas the number admitted following a community circumcision rose after funding withdrawal (6 versus 11 patients). Only a third of British paediatric surgical centres offer a ritual circumcision service, and a significant pro- portion of these were either providing the service without PCT funding, or were reconsidering their decision to continue. CONCLUSIONS: PCT funding withdrawal for ritual circumcision had an impact on our unit's procedural case volume. This represented a cost saving to the trust, despite a higher rate of admissions for postoperative complications. There is an inequality in healthcare provision throughout the British Isles for ritual circumcision, and we feel it is vital to offer support and training to medical and non-medical practitioners who are being asked to perform a greater number of circumcisions in the community.