Stem Cell Transplantation: CD34-Selection Does Not Prolong Survival

Stem Cell Transplantation for Multiple Myeloma: CD34-Selection Does Not Prolong Survival

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. 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. One area in which researchers have been working is in eliminating cancer cells, which may have been present in the blood when it was collected, from the blood (including the stem cells) that is to be infused back into the patient. However, it is not known whether the re-introduction of these cancer cells contributes to relapse; indeed, researchers now report that the effort to eliminate the cancer cells from the blood to be infused does not improve survival.

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.

In addition, the use of high-dose chemotherapy can offer hope for a prolonged survival time for some patients with multiple myeloma. However, high doses of chemotherapy drugs damage the bone marrow, making a stem cell transplantation necessary. The blood collected from the patient before chemotherapy, as part of the autologous stem cell transplantation process, contains approximately 1% stem cells. The rest of the blood collection contains other blood components, and possibly some of the cancer cells that were originally present in the patients bloodstream or bone marrow. To avoid the risk of re-introducing the cancer cells into the patients body, researchers have found a way to identify and select only the stem cells from the collected blood. Stem cells contain a substance, called a CD34 antigen, that cancer cells do not have. Using a scientific technique called the CEPRATE® system, the researchers can detect the CD34 antigen, then remove cells with the CD34 antigen out for infusion, knowing that these are the stem cells. Researchers from several medical institutions recently conducted a study to determine whether the CD34-selection method resulted in improved survival rates for persons with multiple myeloma being treated with high-dose chemotherapy and autologous stem cell transplantation.

One hundred ninety persons who were newly diagnosed with multiple myeloma received high doses of the chemotherapy drugs busulfan and cyclophosphamide, along with an autologous stem cell transplantation. As part of the transplant, patients were assigned to receive either infusion with CD34-selected stem cells or unmodified stem cells after the high-dose chemotherapy regimen. Results showed that there were no differences between the 2 groups in the average time it took for blood cell counts to recover, in the length of hospital stays, or in the number of treatment-related deaths. After an average of 37 months, 36% of persons who received the CD34-selected stem cells had died, compared with 35% of those who received the unselected whole-blood infusion. A recurrence (return of cancer) occurred in 67% of those who received the CD34-selected cells, and 66% of those receiving the unselected whole blood.

These findings show that removal of the cancer cells from the blood to be infused back into the patient may not improve survival time for persons with multiple myeloma who undergo an autologous stem cell transplantation. Other options may be participation in a clinical trial in which other stem-cell selection methods and/or other high-dose chemotherapy regimens are being used. Finally, other types of stem cell transplantation, such as an

allogeneic stem cell transplantation (the stem cells to be infused after high-dose chemotherapy are taken from a related or unrelated donor, not from the patient), may be an option for some persons with multiple myeloma. (Proceedings of the American Society of Hematology, Abstract 3151, p 714a, 1999)

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