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Protective regimen for acute Graft-versus-host disease

Allogeneic hematopoietic-cell transplantation with the use of conditioning regimens of non-myeloablative radiotherapy, chemotherapy, or both to decrease early toxic effects extends the possibility of hematopoietic-cell// transplantation to patients older than 50 years and those with coexisting conditions.

However, acute graft-versus-host disease (GVHD) remains a major problem after non-myeloablative transplantation. Death due to this complication accounts for approximately 50% of the deaths that are not due to a relapse of the neoplasm.

Conditioning with total lymphoid irradiation plus anti-thymocyte serum has been previously shown to protect mice against acute GVHD after hematopoietic-cell transplantation.

Recently, a research team from the Stanford University School of Medicine, Stanford, California, tested this strategy in humans.

In a study published in the September issue of New England Journal of Medicine, 37 patients with lymphoid malignant diseases or acute leukemia underwent an experimental conditioning regimen with 10 doses of total lymphoid irradiation (80 cGy each) plus antithymocyte globulin, followed by an infusion of HLA-matched peripheral-blood mononuclear cells from related or unrelated donors who received granulocyte colony-stimulating factor.

Of the 37 transplant recipients, only 2 had acute GVHD after hematopoietic-cell transplantation. Potent antitumor effects in patients with lymphoid malignant diseases were shown by the change from partial to complete remission. In the transplant recipients who underwent conditioning with total lymphoid irradiation and antithymocyte globulin, the fraction of donor CD4+ T cells that produced interleukin-4 after in vitro stimulation increased by a factor of five, and the proliferative response to alloantigens in vitro was reduced, as compared with normal control subjects and control subjects who underwent conditioning with a single dose of total-body irradiation (200 cGy).

The study concludes that a regimen of nonmyeloablative conditioning of total lymphoid irradiation plus antithymocyte globulin given before hematopoietic-cell transplantation for lymphoid malignant diseases or acute leukemia can markedly decrease the incidence of acute GVHD while retaining the antitumor effect of the graft, and allows graft antitumor activity in patients with lymphoid malignant diseases or acute leukemia treated with hematopoietic-cell transplantation.
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