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

Department of Pediatrics, Section of Allergy and Immunology, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77039, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 01/2009; 122(6):1185-93. DOI: 10.1016/j.jaci.2008.10.030
Source: PubMed


Between 1981 and 1995, 20 children with severe combined immunodeficiency (SCID; median age at transplant, 6.5 [range, 0.5-145] mo, 12 with serious infection) were treated with haploidentical T cell-depleted (anti-CD6 antibody) bone marrow (median number of 5.7 [0.8-18.8] x 10(8) nucleated cells/kg) from mismatched related donors (MMRDs), and 5 children with SCID (median age at transplant, 1.8 [0.5-5.0] mo, 1 with serious infection) were given unmanipulated bone marrow from matched related donors (MRDs). No conditioning or graft-versus-host disease (GvHD) prophylaxis was used.
To assess the outcomes of patients with SCID who received bone marrow from MMRDs or MRDs.
We reviewed the medical records of these 25 consecutive patients with SCID (4 with Omenn syndrome).
Of the 20 patients who received bone marrow from MMRDs, 12 engrafted, 10 survived at a median age of 15.2 [10.0-19.1] years, 4 had chronic GvHD (lung, intestine, skin), 5 required intravenous immunoglobulin, and 8 attended school or college. Two of 5 patients who died had chronic GvHD, and 2 developed lymphoproliferative disease. Of the 5 patients who received bone marrow from MRDs, 5 engrafted, 5 survived at a median age of 23.3 [18.5-26] years, 1 had chronic GvHD (lung, skin), 2 required intravenous immunoglobulin, and 4 attended school or college.
Treatment of critically ill patients with SCID with anti-CD6 antibody T cell-depleted MMRD marrow resulted in an overall 50% long-term survival of patients (83% survival of those engrafted). The principal barriers to long-term survival were delay in diagnosis, life-threatening infection, failure to engraft, and chronic GvHD. Educational goals were achieved in most of the survivors.

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    • "In addition, the anti-T12/CD6 mAb associated with rabbit complement was also used ex vivo for removing T cells from the donor BM, as an attempt to reduce the incidence of acute and chronic GvH disease. These allogeneic CD6-depleted BM transplantations have been used successfully in patients with hematologic malignancies and severe combined immunodeficiency [73, 74]. After BM transplantation, NK cells are reconstituted early, and T cells are detected after four to eight weeks including T-cell functional abnormalities and a significant fraction of CD6-nonexpressing T cells [75]. "
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