Multiple myeloma, a type of cancer called a plasma cell neoplasm, is characterized by the presence of cancerous plasma cells in the bone marrow. The bone marrow (and circulating blood) contains early blood-forming cells, called stem cells, which grow and mature into the 3 blood cell types: white blood cells (protect the body from infection), red blood cells (carry oxygen to the tissues), and platelets (help the blood to clot). The plasma cells are then produced by a type of white blood cell, called lymphocytes, and serve to protect the body from infection. The cancerous plasma cells can crowd out other cells, such as red blood cells; can cause a breakdown of bone; and can collect to form tumors (called plasmacytomas) in the bone. Once symptoms of the disease manifest, persons with multiple myeloma are usually treated with chemotherapy.
For persons with multiple myeloma, initial treatment with very high doses of chemotherapy instead of the standard doses of chemotherapy can sometimes result in increased survival time compared to conventional-dose treatment. Because the high doses of chemotherapy also destroy the young blood cells in the bone marrow, called stem cells, a procedure called an autologous stem cell transplantation is also performed to “rescue” the bone marrow and hasten blood cell production. The stem cells are taken from the patient before the high-dose chemotherapy is administered, are frozen, and then infused back into the patient once the chemotherapy is completed.
The usual treatment regimen for patients with multiple myeloma is high-dose melphalan with or without total body irradiation. Doctors have reached the maximum doses of total body irradiation and/or melphalan that can be given to patients with autologous bone marrow or blood stem cell support. Higher doses of either melphalan or total body irradiation increase the number of patients who will die of complications. However, only 30-35% of patients receiving an autologous transplant using current treatment regimens will have a complete remission. Furthermore all patients with multiple myeloma receiving autologous transplants will probably ultimately have disease recurrence. Thus, newer approaches are needed to eradicate cancerous myeloma cells.
Doctors at MD Anderson Medical Center and the Fred Hutchinson Cancer Research Center have been evaluating a new approach to improving the outcomes of patients receiving autologous transplants for multiple myeloma. Since most of the cancerous myeloma cells are in the skeleton, a targeted radio-pharmaceutical with selective uptake in bone could be more effective by specifically targeting the cancerous cells in bone marrow. Such therapy should be less toxic to other organ systems. One agent that is currently being investigated is radioactive Holmium. Initial studies have established the safety and potential efficacy of radioactive Holmium when combined with high doses of melphalan and total body radiation for the treatment of multiple myeloma.
These doctors have treated 17 patients with melphalan, total body irradiation and Holmium. No patient died of treatment related problems. The complete remission rate was approximately 50% and the partial response rate was approximately 15%.
This clinical trial demonstrated the feasibility and safety of adding increased treatment with a bone seeking isotope without increasing the toxicity of the transplant procedure. This is because the isotope stayed mainly in the bone and did not damage vital organs. These doctors now will standardize this treatment and determine the effects of this treatment on survival of patients with multiple myeloma. (Proceedings of the American Society of Hematology, Vol 94, Issue No 10, Suppliment 1, pp709a, Abstract # 3133, 1999)