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
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.
Available from: Enrique Montero
- "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 . "
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ABSTRACT: CD6 is a 105-130 kDa surface glycoprotein expressed on the majority of T cells and a subset of B cells. The human cd6 gene maps to chromosome 11, and the expression of its protein product is tightly regulated. CD6 mediates cellular adhesion migration across the endothelial and epithelial cells. In addition, it participates in the antigen presentation by B cells and the subsequent proliferation of T cells. CD6 may bind in trans to surface glycoproteins (such as ALCAM and 3A11), or to microbial lipopolysaccharides, and may bind in cis to endogenous ligands (such as CD3 and CD5), and thereby deliver a costimulatory signal. Transinteractions are reinforced during autoimmune diseases (e.g., rheumatoid arthritis (RA), Sjögren's syndrome, and multiple sclerosis) and some cancers. Based on experimental data and on clinical results in RA and psoriasis, we believe that the recent humanized anti-CD6-specific mAb T1h may act as a regulator of the immunological response in addition to its function as an anti-T- and -B cell agent.
01/2010; 2010(6):130646. DOI:10.1155/2010/130646
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ABSTRACT: By intelligently locating a tactile sensor with respect to a
sensed object it is possible to minimize the number of sensed points
required to identify or localize the object. The author applies
principles of statistical decision theory to determine the optimal
sensing location to constrain an object model, maximally based on any
prior object information, including models or previously sensed points.
He shows how information about an object's shape can be combined with
sensory data to produce a probablistic membership function on the
workspace. Utility functions on the workspace are derived which
qualitatively describe the constraining value of obtaining sensory data
at each location in the environment. Also described are techniques of
sequential analysis which are used to process sensory information as it
is acquired. An implementation of these principles is presented, namely,
a two-dimensional sensing problem, using a camera with a restricted
field of view to acquire sparse sensory data, which are used to
discriminate the identity of a shape from among a given set
Robotics and Automation, 1989. Proceedings., 1989 IEEE International Conference on; 06/1989
Thomas' Hematopoietic Cell Transplantation, Third Edition, 10/2007: pages 1 - 8; , ISBN: 9780470987070
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