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)

A six-year-old boy with homozygous beta-thalassemia in the favorable class 1 risk group received a bone marrow transplant, from his histocompatible sister. He developed grade IV skin and eye graft-versus-host disease (GVHD) following varicella zoster reactivation. Despite the appropriate prophylactic use of cyclosporin A (CsA), methotrexate (MTX), and prompt treatment with high-dose steroids, GVHD progressed resulting in total body epidermal necrolysis. Anti-IL-2 receptor monoclonal antibodies (anti-IL-2R moAb) in combination with steroids were administered to selectively block the activated T cells. After 27 days of daily administration, followed by 17 doses of alternate-day therapy with anti-IL-2R moAb, the severe skin and eye GVHD resolved. The patient, at two years posttransplant, has full engraftment and immune reconstitution without chronic GVHD (cGVHD). In conclusion, we suggest that in the HLA-genoidentical bone marrow transplantation setting, very severe and steroid-resistant GVHD can be controlled through the use of anti-IL-2 receptor antibodies which specifically block the activated IL-2 receptor expressing T cells.
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PMID:Blockade of acute grade IV skin and eye graft-versus-host disease by anti-interleukin-2 receptor monoclonal antibody in genoidentical bone marrow transplantation setting. 967 28

Daclizumab, a humanized monoclonal IgG1 directed against the alpha chain of the interleukin-2 receptor (IL-2R), is a competitive inhibitor of IL-2 on activated lymphocytes. To test the hypothesis that specific inhibition of activated lymphocytes in patients with ongoing acute graft-versus-host disease (GVHD) might ameliorate the process, we treated 43 patients with advanced or steroid-refractory GVHD with daclizumab. The first cohort of 24 patients was treated with daclizumab 1 mg/kg on days 1, 8, 15, 22, and 29. On day 43, the complete response (CR) rate was 29% (95% confidence interval [CI], 13%-51%). Survival on day 120 was 29% (95% CI, 13%-51%). A second cohort of 19 patients was treated with daclizumab 1 mg/kg on days 1, 4, 8, 15, and 22. For these patients, the CR rate on day 43 was 47% (95% CI, 24%-71%), and survival on day 120 was 53% (95% CI, 29%-76%). There were no infusion-related reactions and no serious side effects related to daclizumab. Following treatment, there was a reduction in serum concentrations of soluble IL-2R and peripheral blood CD3( + )25(+) lymphocytes, but these changes were not predictive of response. Daclizumab has substantial activity for the treatment of acute GVHD, and the second regimen evaluated is recommended for a controlled study. (Blood, 2000; 95:83-89)
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PMID:Daclizumab, a humanized anti-interleukin-2 receptor alpha chain antibody, for treatment of acute graft-versus-host disease. 1060 89

Competitive inhibition of interleukin 2-dependent lymphocytes by daclizumab demonstrates some beneficial effects in the treatment of graft-versus-host disease (GVHD). Sixteen patients with steroid refractory GVHD received daclizumab (1 mg/kg BW) on d 1, 2 (-5), 7, 14 and 21. Twelve patients suffered from grade III-IV acute GVHD and four patients from extensive chronic GVHD. Responses were observed in nine patients (six acute, three chronic GVHD). Fourteen out of 16 patients acquired infections during daclizumab treatment and three deaths were infection related. Daclizumab demonstrates limited activity and is associated with an increased incidence of infectious complications.
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PMID:Treatment of steroid refractory acute and chronic graft-versus-host disease with daclizumab. 1126 89

In this case report we describe a novel treatment with two chimeric monoclonal antibodies (MoAb) targeting the autoimmune B cell clone responsible for bullous pemphigoid (BP) as a manifestation of steroid refractory chronic graft-versus-host disease (GVHD) that developed after unrelated cord blood transplantation. Monitoring the BP-specific circulating antibodies and CD25-expressing activated T lymphocyte subset led us to combine anti-CD20 (Rituximab) mediated B cell ablation with anti-CD25 (Daclizumab) therapy to block CD4(+) T cell help. Complete clinical and serologic response was achieved within 4 weeks of initiation of therapy allowing global immunosuppression to be dramatically reduced.
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PMID:Combination treatment of bullous pemphigoid with anti-CD20 and anti-CD25 antibodies in a patient with chronic graft-versus-host disease. 1564 Aug 17

An infant with congenital leukemia in complete remission (CR1) received an unrelated donor umbilical cord blood cell transplant from a one-HLA disparate donor. The conditioning regimen consisted of thiotepa, busulfan and cyclophosphamide. GVHD prophylaxis consisted of tacrolimus and mini-methotrexate. Engraftment occurred and a bone marrow aspirate obtained on day 28 showed 100% donor cells. The post-transplant course was complicated by skin and liver GVHD, grade III, that responded to therapy with methylprednisolone, anti-thymocyte globulin and daclizumab (Zenapax), in addition to tacrolimus. A bone marrow aspirate obtained on day 187 showed relapse, with 17% blasts. The patient was then treated for 30 days with recombinant human granulocyte-macrophage colony-stimulating factor treatment (rhGM-CSF). A bone marrow aspirate obtained 17 days after the initiation of rhGM-CSF treatment showed 2% blasts. Ascites was the predominant side-effect of the rhGM-CSF treatment. The patient remains in complete remission 24 months after relapse and 30 months after transplantation. This case documents that rhGM-CSF and withdrawal of immunosuppression can induce a durable complete remission after relapse following an unrelated donor cord blood transplant.
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PMID:Treatment of leukemia relapse with recombinant granulocyte-macrophage colony stimulating factor (rhGM-CSF) following unrelated umbilical cord blood transplant: Induction of graft-vs.-leukemia. 1239 Apr 35

Acute and chronic graft-versus-host disease (GvHD) remain major obstacles to successful allogeneic hematopoietic stem cell transplantation, contributing substantially to morbidity and non-relapse mortality. Better understanding of the immunopathophysiology of GvHD has identified a number of targets for intervention. Among newly developed agents suitable for the prevention and treatment of GvHD, monoclonal antibodies hold much promise. Monoclonal antibodies currently available, such as infliximab and anti-interferon-gamma (anti-IFN-gamma), are capable of blocking of the action of initiating and effector cytokines. Antibodies directed against activated T cells, including daclizumab, visilizumab and ABX-CBL, may offer more specificity than the more broadly acting pan-T-cell-depleting agents. Finally, the clinical investigation of antibodies to adhesion molecules (such as LFA-1), or distal effector mechanisms (such as FasL) may offer another level of specificity. Many of these monoclonal antibodies have already undergone clinical testing. Campath-1H has been used for the prevention of acute GvHD with success. Daclizumab, infliximab, visilizumab, and ABX-CBL have shown promising activity in steroid-resistant acute GvHD in early clinical testing. This review summarizes current experience with monoclonal antibodies in the management of acute and chronic GvHD. Over the next decade, however, the challenge will be to define the relative place of these antibodies in the therapeutic armamentarium for GvHD and their impact on long-term survival.
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PMID:Monoclonal antibodies for the prevention and treatment of graft-versus-host disease. 1293 20

The standard initial therapy for acute graft-versus-host disease (GVHD) is corticosteroids. Daclizumab is a humanized monoclonal antibody against the interleukin 2 (IL-2) receptor expressed on activated T lymphocytes. Because of daclizumab's favorable toxicity profile and response rate in steroid-resistant GVHD, a multicenter, double-blinded, randomized study of corticosteroids with or without daclizumab for initial treatment of acute GVHD was conducted. A total of 102 evaluable subjects of the targeted 166 were enrolled at 5 participating sites. Methylprednisolone at a dose of 2 mg/kg or daily equivalent was given in conjunction with daclizumab 1 mg/kg or placebo on study days 1, 4, 8, and weekly as long as clinically indicated. The groups were balanced for clinical characteristics. GVHD response rates by study day 42 were similar (53% vs 51%; P =.85). The study was halted after a planned interim analysis showed a significantly worse 100-day survival in the group receiving corticosteroids plus daclizumab (77% vs 94%; P =.02). Overall survival at 1 year was also inferior in the combination arm (29% vs 60%; P =.002). Both relapse- and GVHD-related mortality contributed to the increased mortality in the combination group. The combination of corticosteroids and daclizumab should not be used as initial therapy of acute GVHD.
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PMID:Effect of up-front daclizumab when combined with steroids for the treatment of acute graft-versus-host disease: results of a randomized trial. 1513 63

Daclizumab, a humanized IL-2 receptor antagonist, has been found to be safe and effective in adults with refractory graft-versus-host disease (GVHD); however, data describing its efficacy for refractory GVHD in children are limited. We report a series of 14 children who were treated with daclizumab for severe acute and/or chronic corticosteroid refractory GVHD. Patients were treated with 2 mg/kg weekly for 8 weeks followed by 1 mg/kg weekly for 4 weeks. Nine of 14 patients responded to daclizumab as measured by improvement of GVHD symptoms, and the ability to substantially wean corticosteroid dose. Five of 11 patients with acute GVHD had complete symptom resolution, and 2/11 had a partial response. Two of four patients with chronic GVHD had complete symptom resolution. In these patients, daclizumab was only effective in treating skin GVHD. Seven of the nine patients who had a complete or partial response eventually had recurrence of GVHD; however, the GVHD was less severe and no longer corticosteroid refractory. There was no infusional toxicity, and no infections that could be attributable to the drug. Daclizumab is a relatively safe and effective medication for corticosteroid refractory GVHD in children and larger studies are needed to evaluate its role in treatment.
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PMID:Daclizumab for children with corticosteroid refractory graft-versus-host disease. 1624 17

The case report of a 2 year old boy with steroid refractory DBA, treated with allogeneic PBSCT from an HLA matched sibling is presented. Anti-IL2 receptor antibody Daclizumab was used as a prophylaxis for graft versus host disease (GvHD). Complete recovery without any evidence of GvHD ensued.
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PMID:Allogeneic peripheral blood stem cell transplant (PBSCT) using anti-IL2 receptor antibody Daclizumab for the prevention of acute graft versus host disease in steroid refractory Diamond Blackfan anaemia: a case report. 1630 57

In a phase II study, daclizumab was given as single second-line agent to 62 patients with steroid-refractory acute graft-versus-host disease (aGVHD). Complete resolution of aGVHD was achieved in 68.8% of patients. This response rate was significantly associated with a lower number of involved organs and smaller extent of skin involvement. The 4-year event-free survival (EFS) was 54.6%. Grade > or =III aGVHD, > or =2 involved organs at baseline and patient age >18 years were independently associated with lower EFS. Daclizumab could be a suitable alternative treatment for aGVHD, particularly when limited to the skin or gastrointestinal tract.
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PMID:Daclizumab, an efficient treatment for steroid-refractory acute graft-versus-host disease. 1698 86


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