In a recent article published in the journal Bone Marrow Transplantation, researchers reported that a unique approach to improve bone marrow transplants for multiple myeloma patients may improve disease-free survival.
Multiple myeloma is a cancer of the blood that affects the plasma cells-an important part of the immune system that produces antibodies to fight infection and disease. Multiple myeloma is characterized by an excess production of abnormal plasma cells. Symptoms include an increased risk for bacterial infections or impaired immune responses. Myeloma may also damage the kidneys and cause osteoporosis, anemia and an elevated blood calcium level.
Although multiple myeloma is not usually curable, except by allogeneic stem cell transplantation, it can be treated effectively to allow patients to live longer, healthier lives. Treatment options for multiple myeloma include watchful waiting, chemotherapy, radiation therapy and, autologous stem cell transplantation, and in some younger individuals, allogeneic stem cell transplantation.
Stem cells are immature blood cells taken from the bone marrow or blood and frozen and stored until the patient has completed high doses of chemotherapy or radiation. Stem cells may be collected from the patient (autologous transplant) or from a family member or a non-family member whose cells match the patient’s (allogeneic transplant). When these treatments are completed, the stem cells are given back to the patient through an infusion. The cells grow and mature to restore the patient’s blood cells. Following allogeneic stem cell transplantation patients may experience what is known as a graft (the transplanted blood cells) versus tumor effect. This is an immune response in which the immune cells present in the donor’s transplanted blood produce an immune system attack on the transplant recipient’s cancerous cells. A graft-versus-tumor response is usually associated with a generalized graft-versus-host disease where donor lymphocytes damage the skin, gastrointestinal tract and liver of the graft recipient. In the absence of a graft-versus-host disease reaction, there is likely little (if any) graft-versus-tumor effect. Thus, there have been attempts to augment the immune response of donor cells against recipient myeloma cells by vaccinating the donor.
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In this recent study, researchers extracted a protein found on recipient myeloma tumor cells to be used as a target for the immune system. A vaccine was created from the protein, which would produce an immune response among bone marrow transplant (BMT) donors. Researchers anticipated that this immune response would be transferred by donor lymphocytes and enhance the anti-tumor effect of the graft against myeloma cells of the transplant recipient after transplantation.
Five sibling donors were vaccinated prior to the stem cell collection, and transplant recipients also received booster immunizations after they received the transplant. Unfortunately, two of the five patients died within 30 days after BMT due to transplant-related complications. However, immune responses were detected in all three of the remaining BMT recipients. The response lasted for 18 months. Additionally, all three surviving patients were considered to have had a complete response to treatment after receiving BMT. Two of the three patients remained disease free at 7 and 8 years; however, the third died of renal failure 5.5 years after transplantation while in complete remission from the multiple myeloma.
Researchers concluded that vaccinating BMT donors with myeloma proteins produced an immune response that was transferred to allogeneic stem cell recipients by donor lymphocytes. This augmented immune response may improve disease-free survival and may represent a general strategy to enhance the graft-versus-tumor effect in patients with multiple myeloma-especially in transplant recipients who do not have graft-versus-host disease.
Reference: Neelapu S, Munshi N, Jagannath S, et al. Tumor Antigen Immunization of Sibling Stem Cell Transplant Donors in Multiple Myeloma. Bone Marrow Transplantation. 2005; doi: 10.1038/sj.bmt.1705057
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