Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

For treatment of steroid-resistant severe graft-versus-host disease, a murine monoclonal antibody (25.3) against the alpha chain (CD11a) of the lymphocyte function-associated antigen 1 (LFA-1) was infused into a patient with posthepatitic aplastic anemia who had undergone allogeneic bone marrow transplantation. The monoclonal antibody infusion was well tolerated and resulted in appreciable improvement in symptoms of gastrointestinal illness such as diarrhea and abdominal pain, suggesting that this antibody may be useful for controlling severe acute graft-versus-host disease.
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PMID:Anti-LFA-1 antibody treatment of a patient with steroid-resistant severe graft-versus-host disease. 148 52

Bone marrow transplantation is a therapeutic treatment for many life-threatening hematologic disorders, especially leukemia and certain immune deficiency diseases. However, acute graft-versus-host disease is often associated with bone marrow transplantation. In mice, allogeneic GVHD appears to be mediated by both host natural killer cells and donor T cells. In vitro and in vivo experiments demonstrate that treatment with either YN1/1.7 or M17/4.2 mabs is immunomodulatory and inhibits both the mixed lymphocyte reaction and natural killer cell activity. In addition, utilizing an allogeneic model of acute, lethal GVHD with C57B1/6 mice as donors and sublethally irradiated BDF1 mice as recipients, treatment of host mice with anti-LFA-1 alpha (M17/4.2) or anti-MALA-2 (YN1/1.7) mabs at a dose of 10 mg/kg/day for 10 days significantly reduced GVHD and enhanced survival. Mabs to lymphocyte adhesion molecules such as LFA-1 alpha and MALA-2 may provide a useful therapy for the treatment of GVHD.
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PMID:Reduction in the severity of graft-versus-host disease and increased survival in allogenic mice by treatment with monoclonal antibodies to cell adhesion antigens LFA-1 alpha and MALA-2. 165 92

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

We have retrospectively analyzed the outcome of bone marrow transplantation (BMT) in 14 patients with leukocyte adhesion deficiency (LAD) performed in two centers between 1981 and 1993. Five patients received BMT from HLA-identical donors. Nine received T-depleted marrow from two HLA antigen- or haplotype-incompatible parents. Conditioning regimen consisted of chemotherapy exclusively in 13 patients and associated with total body irradiation (TBI) in one patient. In five cases, failure of engraftment occurred as a result of either insufficient myeloablation (n = 3) or, possibly, graft rejection in two cases of moderate phenotype of LAD. The second conditioning regimen consisted of TBI and chemotherapy with the use of anti-lymphocyte function-associated antigen 1 (LFA-1) and anti-CD2 monoclonal antibodies for patients with the moderate phenotype of LAD. These patients were successfully retransplanted. Eight patients developed acute graft-versus-host disease (GVHD). Chronic GVHD occurred in five cases. GVHD led to the death of three patients. Ten patients are alive and well 12 months to 12 years after BMT. Chimerism is full in six of these patients and mixed but stable in four with variable proportion of donor leukocytes. One patient with less than 15% donor leukocytes has mild gingivitis, while the others are well. Sequelae from BMT are limited in two cases to growth retardation caused by TBI. Success of BMT in cases of LAD including seven of nine recipients of HLA nonidentical marrow indicates that this procedure can be proposed as a curative approach to LAD regardless of an available HLA-identical donor. Great care should be taken in GVHD prophylaxis and treatment.
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PMID:Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency. 763 73

Human cord blood is an attractive alternative to marrow-derived stem cells for transplantation. Experiences with cord blood transplants suggest that graft-versus-host disease (GvHD) may be less readily induced, even in the face of HLA differences. However, this decreased potential for GvHD might also abrogate the graft-versus-leukemia (GvL) effects of the transplant. The GvL potential might be doubly compromised since cord blood NK activity is also decreased. We have compared alloreactivity, NK cell activity and lymphokine-activated killer cell (LAK) activity of cord blood mononuclear cells with adult mononuclear cells. We find a reduced (but not absent) alloproliferative, allostimulatory and allocytotoxic capacity of cord blood mononuclear cells. Phenotyping revealed no significant differences in the proportion of T cells in cord-versus-adult blood, but cord blood T cells were nearly all of the naive CD45RA subset. Expression of LFA-1 alpha and LFA-1 beta was normal on resting cord T cells; however, they expressed significantly less ICAM-1 (CD54) than did adult PBMC. Cord blood B cells and monocytes expressed normal levels of HLA Class II. Although no differences were found in NK cell percentages or subsets in resting cord blood, cord blood NK activity was very low. However, LAK activity was much more readily induced in cord blood as compared to adult PBMC, which could be explained in part by a higher frequency of LAK precursors (LAKp). Cord blood LAK cells were readily able to lyse fresh leukemia targets from patients with ALL, AML, and CML.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of cord blood lymphocyte subpopulations. 792 75

Leukocyte adhesion deficiency type I (LAD-I) is an inherited immunodeficiency disorder caused by defective expression of the leukocyte integrins, namely, lymphocyte function-associated antigen 1, Mac-1, and p150, 95, and is associated with obstructed cell adhesion, migration, and phagocytosis. Patients suffer from various bacterial or fungal infections and their prognoses are poor. The only curative treatment is hematopoietic stem cell transplantation. Conventional myeloablative transplantations have been performed, but with unsatisfactory results. We performed the first successful nonmyeloablative unrelated marrow transplantation for a 20-year-old female LAD-I patient, who suffered from recurrent and occasionally life-threatening infections such as cellulitis, gingivostomatitis, and sepsis. We adopted a preparative regimen with fludarabine, cyclophosphamide, and low-dose total-body irradiation, and tacrolimus and short-term methotrexate as immunosuppressants. This procedure was sufficiently immunosuppressive to obtain stable engraftment without remarkable complications, and graft-versus-host disease was controllable. Dramatic improvement of her disease was observed, supported by the normal expressions of integrins. Twenty one months after transplantation, she is well with a Karnofsky score of 100. Thus, nonmyeloablative transplantation is considered a feasible method for LAD-I.
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PMID:Successful nonmyeloablative bone marrow transplantation for leukocyte adhesion deficiency type I from an unrelated donor. 1767 74