Risk of graft-versus-host disease (GVHD) in lymphoma and leukemia patients undergoing allogeneic stem cell transplantation can be reduced by first treating patients with total lymphoid irradiation and antithymocyte globulin, according to a study published in the New England Journal of Medicine .
A stem cell transplant is a procedure in which stem cells destroyed by high-dose cancer therapy are replaced with healthy stem cells. The procedure allows for more rapid recovery and production of much needed red blood cells, white blood cells, and platelets.
During an autologous stem cell transplant, stem cells are collected directly from the patient prior to the delivery of high-dose chemotherapy. Cells are re-infused following treatment. In contrast, an allogeneic stem cell transplant involves stem cells collected from a donor.
An important benefit of an allogeneic stem cell transplant is that donor cells mount an attack against cancer cells (graft-versus-tumor effect). Unfortunately, donor cells may also attack a patient’s healthy tissue, producing GVHD. Researchers have therefore focused on developing improved approaches to allogeneic stem cell transplants that reduce the risk of GVHD while still maintaining a graft-versus-tumor effect.
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An approach that has reduced risk of GVHD in mice is the combination of total lymphoid irradiation (repeated low-dose radiation therapy to lymphoid tissue) and treatment with anti-T-cell antibodies prior to stem cell transplantation.
Researchers at Stanford University tested this approach in humans in a study of 37 patients with lymphoma or leukemia. Patients received a conditioning program of 10 doses of radiation therapy to lymphoid tissue, along with antithymocyte globulin (Thymoglobulin®), prior to receiving an allogeneic stem cell transplant. (Antithymocyte globulin suppresses some types of immune cells.) In the 100 days after transplantation, only two of the 37 patients developed GVHD. This is a much lower rate of GVHD than is generally observed. Furthermore, 12 of 16 patients with lymphoma in partial remission at the start of the study were in complete remission after stem cell transplantation. This suggests that the stem cell transplant retained its graft-versus-tumor effect.
The researchers conclude that treatment of leukemia and lymphoma patients with total lymphoid irradiation along and antithymocyte globulin prior to allogeneic stem cell transplantation reduces the risk of GVHD while preserving the antitumor effectiveness of the transplant.
Reference: Lowsky R, Takahashi T, Liu YP et al. Protective conditioning for acute graft-versus-host disease. New England
Journal of Medicine . 2005;353:1321-31.
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