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According to a recent article published in the journal Blood, sequential stem cell transplants, including an autologous stem cell transplant followed by an allogeneic transplant, appears promising for the treatment of relapsed or refractory multiple myeloma.

Multiple myeloma is a cancer involving important immune (infection-fighting) cells called plasma cells. Plasma cells aid the body in fighting infection by producing specialized proteins called antibodies that have the ability to target and/or kill foreign cells. In multiple myeloma, cancerous plasma cells produce abnormal and excessive antibodies that do not have the ability to properly fight infection. In addition, the cancerous plasma cells accumulate in the bone marrow, suppressing the normal formation and function of other cells that are necessary for normal production of blood cells and immune functions. The excessive accumulation of cancer cells in the bone marrow ultimately leads to the formation of tumors in the bone and to the breakdown of bone. Furthermore, the cancerous plasma cells secrete dysfunctional antibodies, referred to as M proteins, which can be measured in the blood. Once multiple myeloma stops responding to standard therapies, it is referred to as “refractory”. Patients with refractory multiple myeloma are currently left with few effective treatment options and long-term survival is suboptimal.

One type of therapeutic approach for multiple myeloma is a stem cell transplant. A stem cell transplant involves the use of high doses of chemotherapy and/or radiation therapy in an attempt to kill as many of the cancer cells as possible. However, the high doses of therapy also kill healthy cells in a patient, resulting in an increased risk for severe side effects. Common and life-threatening side effects from high doses of therapy are low levels of blood cells. There are 3 major types of blood cells: white blood cells that fight infection, red blood cells that carry oxygen to tissues, and platelets that aid the blood in clotting. Stem cells are immature blood cells that are produced in the bone marrow and can be found in circulating (peripheral) blood. The procedure of an autologous stem cell transplant involves the collection of a patient’s stem cells prior to high dose therapy, which are frozen and re-infused following therapy in order to restore blood cell levels. An allogeneic stem cell transplant refers to the use of a donor’s stem cells. Donor cells tend to recognize the cancer cells as foreign, and mount an attack against them. However, they may also recognize healthy tissue of the patient as foreign and mount an attack against the healthy tissue. This is called “graft versus host disease” (GVHD), and can be acute or chronic. Researchers are now using lower doses of therapy prior to allogeneic stem cell infusion, to reduce side effects from therapy while maintaining the anti-cancer effects of the donor stem cells. This procedure is referred to as a “mini” transplant or a non-myeloablative stem cell transplant.

Over the past decade, autologous stem cell transplantation has emerged as a standard form of therapy for patients with multiple myeloma. Compared to conventional-dose chemotherapy, autologous transplants following high-dose chemotherapy (melphalan) improves response rates and overall survival, especially in patients who respond poorly to initial chemotherapy. However, all patients receiving a single autologous transplant ultimately relapse. Researchers have also shown that two autologous stem cell transplants or a second autologous stem cell transplant at the time of disease progression can further prolong survival but do not cure the disease.

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Recently, a multi-institutional clinical trial was conducted to evaluate the effectiveness of treatment utilizing an autologous stem cell transplant followed by a mini allogeneic stem cell transplant for recurrent multiple myeloma. The reason for this type of therapeutic approach is to reduce the number of cancer cells in the body with an autologous stem cells transplant, so that the donor stem cells have a small number of cancer cells to attack. This type of therapy can be performed on an outpatient setting. This trial involved 54 patients, with ages up to 71 years. The allogeneic stem cell transplant was administered 2 months following the autologous transplant. Complete disappearances of detectable cancer (complete response) occurred in 57% of patients. Approximately 2 years following treatment, 78% of patients were alive, and the estimated progression-free survival is 55%. Acute GVHD occurred in 40% of patients, and chronic GVHD occurred in 46% of patients. Treatment-related mortality was 17%, with the major cause of death being GVHD.

The researchers concluded that an autologous stem cell transplant followed by a non-myeloablative allogeneic transplant is highly active, producing a significant number of complete responses in patients with relapsed or refractory multiple myeloma. Patients with refractory multiple myeloma may wish to discuss with their physician the risks and benefits of stem cell transplantation or the participation in a clinical trial evaluating novel treatment strategies.

Reference: Maloney DG, Molina AJ, Sahebi F, et al. Allografting with Nonmyeloablative Conditioning Following Cytoreductive Autografts for the Treatment of Patients with Multiple Myeloma.

Blood. 2003;102:3447-3454

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