Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085110 (SCID)
 11,041 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-six infants and children suffering from either inherited immunodeficiency disorders (Wiskott-Aldrich syndrome, functional T-cell immunodeficiency with or without HLA class II expression deficiency), malignant osteopetrosis, or Fanconi's anemia received HLA-nonidentical bone marrow transplantation (BMT) from related donors. Bone marrow was T-cell depleted to reduce the risk of graft-versus-host disease (GVHD). To prevent graft failure, a mouse monoclonal antibody specific for the CD11a-lymphocyte function-associated antigen 1 (LFA-1) molecule was infused into the patients. Eleven patients received five infusions of 0.1 mg/kg every other day from day -3 to +5. Thirty-five patients received 0.2 mg/kg daily from day -3 to +6. The overall sustained engraftment rate was 72% instead of 26.1% in a historical control group of 24 patients similarly treated except for the infusion of the anti-LFA-1 antibody. No late rejection occurred. The T-cell depletion method (E-rosetting or Campath IM plus complement) resulted in different rate of engraftment (83.3% v 57.9%, respectively, P = .05). Engraftment rate was slightly but not significantly influenced by the degree of HLA incompatibility between donor and recipient. Acute GVHD of grade II or more occurred in 35.5% of the patients and the rate of chronic GVHD was 12.9%. The overall actuarial survival rate with a functional graft is 47.3% with a mean follow-up of 28.0 months for patients with immunodeficiency and osteopetrosis, while none of the four patients with Fanconi's anemia survived. The development of full T-cell functions took on the average 6 months and of full B-cell functions 10 months. Significant infectious problems developed in the majority of the patients during the posttransplant course. Epstein-Barr virus-induced B-cell proliferative syndromes were observed in seven patients, six of whom had Wiskott-Aldrich syndrome. Correction of immunodeficiency was comparable in terms of kinetics and quality with that observed in patients with severe combined immunodeficiency undergoing HLA-nonidentical BMT. Correction of osteopetrosis appears not to be different from what has been observed after HLA-identical BMT. The in vivo use of an anti-CD11a-LFA-1 antibody as an additional immunosuppressive therapy in HLA-nonidentical BMT may thus promote engraftment and survival with correction of the primary disease in a significant number of patients with life-threatening immunodeficiency and osteopetrosis, but not with Fanconi's anemia.
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PMID:Reduction of graft failure by a monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi's anemia: a European Group for Immunodeficiency/European Group for Bone Marrow Transplantation report. 198 91

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 x 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.
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PMID:In vitro T cell depletion using Campath 1M for mismatched BMT for severe combined immunodeficiency (SCID). 905 Dec 41

We previously reported that 4C8 monoclonal antibody (mAb) provides a costimulatory signal to human CD4+ T cells and consequently induces regulatory T (Treg) cells, which are hypo-responsive and suppress the polyclonal response of bystander CD4+ cells in a contact-dependent manner. In this study, we identified the antigen of 4C8 mAb as CD52. Costimulation with Campath-1H, a humanized anti-CD52 mAb, also induced Treg cells. Anti-CD52-induced Treg cells suppressed the proliferation of both CD4+ and CD8+ T cells provided with polyclonal or allogeneic stimulation. When Treg cells were induced from Staphylococcal enterotoxin B (SEB) treated cells, they suppressed the response to SEB more efficiently than that to another superantigen, SEA. Furthermore, anti-CD52-induced Treg cells could be expanded by culture with IL-2 followed by CD52-costimulation, and co-injection of expanded Treg cells suppressed lethal xenogeneic graft versus host disease (GvHD) reactions in SCID mice caused by human peripheral blood mononuclear cells (PBMCs).
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PMID:CD52 is a novel costimulatory molecule for induction of CD4+ regulatory T cells. 1679 37

Graft failure is a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). We used a nonmyeloablative conditioning regimen consisting of the lympho-depleting humanized CD52-antibody Campath-1H and fludarabine to rescue 12 consecutive children age 9 months to 17 years with engraftment failure after initial myeloablative HSCT. Primary diagnoses included lymphohematologic malignancies (n=6), severe combined immunodeficiency syndrome (SCID) (n=4), and metabolic diseases (n=2). The same stem cell donor was used as for the primary graft: mismatched family member (n=7), matched unrelated donor (n=4), or matched related donor (n=1). The patients received doses of CD34+ cells that did not significantly differ from those used in the initial, failed transplant. At a median follow-up of 51 months (range, 4 to 84 months), 6 of 6 patients with nonmalignant diseases and 4 of 6 patients with malignancy were alive. Two patients died, 1 patient from pulmonary toxicity and 1 from relapse, at 51 days and 8 months posttransplantation, respectively. All 12 patients initially achieved sustained neutrophil engraftment and complete donor chimerism by day 28. Six patients received donor lymphocyte infusion (DLI) after "rescue" therapy to maintain donor chimerism. At 6 months, 4 patients had complete donor cell engraftment, 4 had 15% to 89% stable donor chimerism, and 3 had developed secondary graft failure. This conditioning regimen was generally well tolerated; 4 of the 12 patients never became neutropenic, and 9 never became thrombocytopenic. Only 1 patient developed graft-versus-host disease (GVHD; grade 1), and none had chronic GVHD. Thus, the regimen that we describe can be used with minimal toxicity to effectively overcome graft failure after myeloablative HSCT in children.
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PMID:Successful treatment of stem cell graft failure in pediatric patients using a submyeloablative regimen of campath-1H and fludarabine. 1894 Jun 85