No abstract

Summary:Bone marrow transplantation (BMT) from siblings is the treatment of choice for severe combined immunodeficiency (SCID). The objective of this study was to evaluate the efficiency of BMT from matched unrelated donors (MUD) in congenital immunodeficiencies when a sibling donor is unavailable. Sixteen consecutive patients with SCID (n = 9) and CID (n = 7), were referred for an unrelated donor search. Acceptable donors were found for all patients. Fifteen patients received busulfan and cyclophosphamide pretransplant conditioning. One patient had an early loss of graft and was reconditioned using cyclophosphamide and total body irradiation. The graft-versus-host disease (GVHD) prophylaxis used was methylprednisolone, cyclosporin A with or without methotrexate. Neutrophil engraftment was rapid and was achieved in all patients within a mean of 15.4 days. Only 13 episodes of fever were recorded shortly after BMT. GVHD of grade II or more was apparent in 2/9 (22%) of SCID patients and in 4/7 (57%) of CID patients. Overall survival was 75% with a mean follow-up of 47.4 months (range 18-101). Six out of nine SCID patients (67%) and 6/7 (86%) of CID patients are alive and well. Eleven patients had normal humoral immunity, and cell-mediated immunity as measured by flow cytometry and mitogenic responses, was intact in all patients. Intradermal candida skin test was positive in 9/10 patients tested. We conclude that BMT from MUD results in rapid engraftment and is therefore associated with a low rate of infection contributing to the improved survival rate. Attempts to use alternative procedures have been less successful. Immunologic reconstitution following fetal thymus and/or liver transplantation is inconsistent; engraftment is achieved in less than one third of cases and a survival rate of less than 20% has been reported. 4,5 T lymphocyte-depleted, haploidentical bone marrow, usually of parental origin, is regarded by many transplant centers as the treatment of choice when fully matched sibling donors are unavailable. Although survival for all types of SCID hovers around 50%, 6 recent preliminary experience shows a higher survival rate (70-78%) in selective SCID phenotypes mainly including T − B + SCID 7,8 and ADA deficiency 8 using this method. However, this approach has serious limitations, including prolonged time to engraftment, 9-12 and very slow B lymphocyte engraftment, which ranges in large series of patients from 40 to 70%. [9][10][11][12][13]

We describe here four patients who appear to have similar clinical and immunological features which constitute a novel syndrome. The patients present with short stature owing to spondylometaphyseal dysplasia and with severe infections as the result of a combined humoral and cellular immune deficiency. Presumably because of dysregulation of the immune system, all patients also developed autoimmune manifestations.