In vitro T cell depletion using Campath 1M for mismatched BMT for severe combined immunodeficiency (SCID)

Abstract

Summary:the mature T cells from the donated marrow. 2 This approach has subsequently been successful in over half of the transplanted children with SCID. Graft failure is much Bone marrow transplantation is the only curative treatment for children with severe combined immunodefiless common in children than in older leukaemic patients given similarly treated marrow perhaps because children ciency (SCID). In the absence of an HLA-identical sibling, haploidentical parental donor marrow can be used with SCID lack the alloreactive immune responses that mediate graft rejection. 3-5provided it is depleted of T cells to prevent otherwise inevitable GVHD. Campath 1M has been successfully T cell depletion has been accomplished by a variety of methods including physical separation with soya bean lecused for this procedure in several centres. In our centre 17 SCID patients plus one with combined immunodefitin and sheep erythrocyte rosetting, 6 as well as immunochemical methods using monoclonal antibodies to lymphocyte ciency (CID) were transplanted with Campath 1M T cell-depleted bone marrow. Progenitor cell recovery, surface antigens, such as Campath 1M in vitro and Campath 1G added to the bag of donor marrow or infused in before and after T cell depletion, was monitored using granulocyte-macrophage colony-forming cell assays vivo. 7,8 We describe a series of 18 T cell-depleted transplants carried out in our BMT centre over the past 8 years, (GMCFU) and CD34 analysis. The numbers of GMCFU/kg transplanted correlated with engraftment during which time the method of marrow manipulation during T cell depletion was changed in an attempt to conform and survival post-transplant and monitoring CD34+ cell numbers in the T cell-depleted marrow pretransplant with other European centres who mainly used physical methods of T cell depletion. Unfortunately this change may be an additional indicator of successful engraftment. Use of a buffy coat marrow preparation appeared to contribute to several failures of engraftment. We therefore attempted to identify markers that would prewith restriction of the number of T cells to Ͻ5 × 10 5 /kg was associated with graft failure in four and death in dict lymphoid engraftment and our results suggest that the number of both CD34 + cells and GMCFU infused per kg five of eight children, probably because too few stem cells were infused. T cell depletion of a mononuclear cell correlates with sustained engraftment and survival following T cell-depleted donor marrow transplantation in preparation of donor marrow with no arbitrary ceiling of infused T cells is highly effective at preventing clinipatients with SCID. cally important GVHD and cured nine out of 10 children transplanted with such material.

Long-term immune reconstitution after anti-CD52–treated or anti-CD34–treated hematopoietic stem cell transplantation for severe T-lymphocyte immunodeficiency

“…Anti-CD52 and anti-CD34 treatment was performed on whole, freshly harvested marrow, as previously described. 5,8 The following parameters were analyzed: myeloid chimerism, T-lymphocyte number and chimerism, CD3 1 /CD4 1 /CD45RA 1 /CD27 1 and CD3 1 / CD4 2 /CD45RA 1 /CD27 1 (naive) T-lymphocyte number, B-lymphocyte number and chimerism, memory B-lymphocyte (CD19 1 /CD27 1 /IgM 1 ) and classswitched memory B-lymphocyte (CD19 1 /CD27 1 /IgM 2 ) number, and serum IgG, IgA, and IgM levels, as well as specific antibody levels to tetanus toxoid, Haemophilus influenzae type B, and pneumococcal polysaccharide antigens after vaccination.…”

Long-term outcomes of nonconditioned patients with severe combined immunodeficiency transplanted with HLA-identical or haploidentical bone marrow depleted of T cells with anti-CD6 mAb

“…This is similar to the rates of engraftment (59% to 70%) for patients who received a MMRD transplant regardless of conditioning. 17,22,39 When survivors of MMRD recipients (with some MRD recipients) who received no conditioning were assessed, a higher rate of engraftment was determined (96%) 2,6 compared with our study. Engraftment of B cells was much lower, as seen in BMT regimens with or without conditioning.…”

Clinical course of patients with major histocompatibility complex class II deficiency

“…All BMTs were done using bone marrow cells aspirated from iliac crests of donors (table3). In cases where T cell depleted grafts were infused, in vitro T cell depletion was accomplished using Campath antibody treatment 6. Three BMT recipients died within six weeks of transplantation of overwhelming viral (CMV, parainfluenza III pneumonitis, enterovirus encephalitis).…”