Rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease.
ABSTRACT We prospectively evaluated the safety and efficacy of the anti-CD20 chimeric monoclonal antibody rituximab for the treatment of corticosteroid-refractory chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation. Seven patients were treated with 375 mg/m(2) rituximab weekly for 4 consecutive weeks. Rituximab was well tolerated with no severe toxicity observed during treatment. At 1 year, 3 patients showed a partial response to rituximab therapy, 3 had stable disease, and 1 had progressive disease. Rituximab allowed a reduction in the dose of steroids in 4 patients. Responsive manifestations included mild to moderate skin and oral lesions, and immune hemolytic anemia, and thrombocytopenia. Severe manifestations involving the skin, fascia, and eye did not respond to treatment. These observations suggest that rituximab therapy may be effective for select patients with corticosteroid-refractory chronic GVHD that is not advanced.
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ABSTRACT: Despite recent reductions in transplant-related mortality, post-transplant complications such as graft-versus-host disease (GvHD) remain major obstacles to the successful application of allogeneic hematopoietic transplantation. Steroid-refractory GvHD has a poor outcome. Although there are a variety of new approaches to the treatment of refractory GvHD, many have limited evidence of efficacy. Other approaches appear to be unacceptably toxic. It would be preferable to improve GvHD prophylaxis. There is good evidence that rates of GvHD can be reduced without unacceptable reduction of the graft-versus-leukemia effect or compromising overall survival. However, prophylactic measures aimed at reducing T-cell numbers or functions are associated with high rates of reactivation of latent viruses. New technologies that allow rapid generation of virus-specific T-cells show promise to reduce the frequency and severity of such reactivations and have the potential to revolutionize the approach to post-transplant infectious complications.Future Oncology 12/2012; 8(12):1549-65. · 3.20 Impact Factor
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ABSTRACT: Anti-CD20 monoclonal antibodies (MoAbs), employed in treating CD20(+) lymphomas and autoimmune diseases, appear to have broader functions than just eradicating malignant B-cells and decreasing autoantibody production. Rituximab-induced T-cell inactivation, reported both in-vitro and in-vivo, may contribute to the increased risk of T-cell-dependent infections, observed in patients receiving this therapy. T-cell polarization into a suppressive phenotype, often observed in patients receiving rituximab for autoimmune disorders, was reported to be associated with prolonged remissions. Elimination of B-cells serving as antigen-presenting cells, thereby causing impaired T-cell activation, could play a significant role in induction of these changes. Direct binding of rituximab to a CD20(dim) T-cell population, inducing its depletion, may contribute to the decreased T-cell activation following rituximab therapy. Further investigation of the complex network through which rituximab and new anti-CD20 MoAbs act, would advance the employment of these agents in different clinical settings.Blood reviews 08/2013; · 7.19 Impact Factor
- Haematologica 04/2013; 98(4):e40-1. · 5.94 Impact Factor