Hematopoietic stem cell transplantation (HSCT) is the treatment of choice for severe combined immunodeficiency (SCID). There remains debate on whether to pre-condition with chemotherapy prior to infusion of stem cells. We aimed to determine the long-term progress of classic SCID patients who had undergone HSCT infusion at our centre, with respect to clinical outcome and immune comparing outcome based on transplant at <3 or >3 months of age, and molecular diagnosis. A retrospective case notes review of patients undergoing a first HSCT infusion for classic SCID from 01/1995 to 02/2011, surviving > 2 months. Patients with previous HSCT were excluded. Parameters analyzed included clinical outcome, chimerism, lymphocyte subsets including recent thymic emigrants, specific antibody levels and Ig replacement. Statistical analysis was performed using c 2 (Fisher exact test) and nonparametric wilcoxon rank sum. A 2-sided p value < 0.05 was considered significant. Twenty seven of 100 patients with SCID treated fulfilled the study criteria; 10 had ADA deficiency, 7 had T-B-NK+ phenotype, 8 had CgC/JAK3 SCID, and 2 had other forms of SCID. 12 were transplanted < 3 months of age, median age at HSCT was 3 months (range 0-8 months). Twenty had infection at diagnosis, all > 3 months. Eleven had MSD, 1 MMSD, 5 MFD, 3 MMFD, 6 MUD, 1 MMUD. Twenty received GvHD prophylaxis. Median follow up was 80 months (2-187). Seven developed grade II-IV GvHD, 3 grade III. Five were re-transplanted, 2 received boost infusion for poor engraftment (1 CgC, 1 T-B-NK+), 3 received a conditioned HSCT (3 T-B-NK+). TRM was 11% (1 ADA, 2 T-B-NK+). Neurological and autoimmune complications were more common in the ADA and T-B-NK+ groups. Recent thymic emigrants were most commonly present in the CgC/JAK3 and ADA groups, and absent from the T-B-NK+ group. The ADA group had the most complete donor chimerism including myeloid chimerism, T-B-NK+ SCID only achieved donor T cell chimerism. Most ADA patients discontinued IVIG, compared to none with T-B-NK+ SCID. HSCT infusion is an effective treatment for SCID. Best results are obtained if transplanted < 3 months of age. Establishment of donor B cell chimerism may require additional therapies to achieve engraftment within the stem cell niche in all but ADA SCID.

BACKGROUND:SCID can be cured by BMT. Depletion of mature T cells from BM has enabled HLA non-identical stem-cell transplantation. We report the outcome of 30 patients treated with 37 T-cell depleted BMT procedures using CAMPATH-1M in vitro between 1987-98 in a single center.METHODS:Immune reconstitution and quality-of-life were assessed in 19 longterm survivors. All but two received pre-transplant conditioning. T- and B-cell chimerism, numbers and function were analyzed during a median follow-up of 5.3 years (range 1.33-12).RESULTS:The overall engraftment rate was 59%, six children required repeated BMT and the survival rate was 63%. All have donor T cells, 58% normal T-cell numbers and 74% normal T-cell function. Of 17 evaluated, 16 patients (94%) have normal IgM and IgG levels, and production of specific Abs to protein Ags, but only 5/16 (31%) have a good response to pneumococcal polysaccharide. Early and late post-BMT complications were rare and there were no delayed deaths. Only one child continues on long-term i.v. Ig 4-years post-BMT. Eleven children died (37%).DISCUSSION:CAMPATH-1M T-cell depleted BMT for SCID resulted in 63% survival. Deaths of 11 children were mainly due to pre-existing infections. Seventeen of 19 long-term survivors have normal immune function and good quality-of-life.

Bone marrow transplantation is the only curative treatment for children with severe combined immunodeficiency (SCID). In the absence of an HLA-identical sibling, haploidentical parental donor marrow can be used provided it is depleted of T cells to prevent otherwise inevitable GVHD. Campath 1M has been successfully used for this procedure in several centres. In our centre 17 SCID patients plus one with combined immunodeficiency (CID) were transplanted with Campath 1M T cell-depleted bone marrow. Progenitor cell recovery, before and after T cell depletion, was monitored using granulocyte–macrophage colony-forming cell assays (GMCFU) and CD34 analysis. The numbers of GMCFU/kg transplanted correlated with engraftment and survival post-transplant and monitoring CD34 + cell numbers in the T cell-depleted marrow pretransplant may be an additional indicator of successful engraftment. Use of a buffy coat marrow preparation with restriction of the number of T cells to <5 × 10 5 /kg was associated with graft failure in four and death in five of eight children, probably because too few stem cells were infused. T cell depletion of a mononuclear cell preparation of donor marrow with no arbitrary ceiling of infused T cells is highly effective at preventing clinically important GVHD and cured nine out of 10 children transplanted with such material.