The Cytogenetic Abnormality, 13q14, is Present in Half of All Patients with Multiple Myeloma and Predicts for a Poor Outcome with Conventional Chemotherapy Treatment
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 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.
Persons with multiple myeloma are treated with combination chemotherapy or combination chemotherapy followed by high-dose chemotherapy. For persons with multiple myeloma, initial treatment with very high doses of chemotherapy instead of the standard doses of chemotherapy results in increased survival time. Because the high doses of chemotherapy also destroy the young blood cells in the bone marrow 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. Stem cells are collected from the peripheral blood after chemotherapy and growth factor administration or following a growth factor alone by a technique call apheresis. If collection is performed early in the treatment course enough stem cells can be harvested to support several courses of high-dose chemotherapy. If delayed until a lot of chemotherapy has been given it may not be possible to collect enough stem cells.
The outcomes for patients with multiple myeloma treated with conventional chemotherapy are variable and it is important for doctors to recognize at diagnosis patients who will do poorly with different types of treatments. Some of the factors that predict for poor outcome include high blood levels of beta-2 microglobulin, low hemoglobin blood levels and low albumen levels. More recently cytogenetic abnormalities have been associated with a poor outcome following conventional-dose chemotherapy or high-dose chemotherapy with autologous peripheral blood stem cell support.
Doctors in Austria have tested for a specific chromosomal abnormality, 13q14, which occurs in myeloma cells. Using a test called interphase fluorescence in situ hybridization (FISH) they were able to detect the 13q14 chromosame in approximately half of persons with multiple myeloma. The presence of the 13q14 abnormality was associated with higher levels of beta-2 microglobulin and a higher percentage of myeloma cells in the bone marrow compared to persons without this abnormality. In addition patients with the 13q14 abnormality had faster growing cancer cells. Following conventional dose treatment 41 % of patients with the 13q14 abnormality had a response compared to 79% of patients without the abnormality. The average survival of patients with the 13q14 abnormality was 24 months compared to over 60 months for persons without this abnormality. (
Blood, Vol 95, Issue No 6, pp 1925-1930 2000)
Other doctors in the US have found that the outcomes for patients with 13q14 following high-dose chemotherapy with autologous peripheral blood stem cell support were also worse than for patients without this abnormality. However, they found that patients with the 13q14 abnormality survived better if they received a second course of high-dose chemotherapy within 6 months of the first course. These doctors advise collection of blood stem cells early in the treatment course for support of two courses of high-dose chemotherapy given within 6 months of diagnosis. (Blood, Vol 93, No 1, pp 55-65, 1999)
Persons in good clinical condition with multiple myeloma with the 13q14 abnormality should receive aggressive treatment. Patients with this abnormality should consider enrolling in a clinical trial aimed at improving the outcome of poor risk patients. One option would be to receive two or more courses of high-dose chemotherapy supported by autologous blood stem cells. Another option is to receive an allogeneic bone marrow or peripheral blood stem cell transplant (the stem cells to be infused after high-dose chemotherapy are taken from a related or unrelated donor, not from the patient). Allogeneic bone marrow or blood stem cell transplant will produce complete remissions in over half of all patients and many will become long-term survivors but 40-50% will die of treatment related complications. More recently the doses of chemotherapy and radiation therapy given before an allogeneic bone marrow or blood stem cell transplant have been reduced resulting in less treatment related deaths. In this form of “mini-transplant” the immunological effect of the graft against the cancer is relied on for cure making this a promising treatment for patients with multiple myeloma.