High-dose chemotherapy (HDC) and/or irradiation followed by an allogeneic stem cell transplantation (SCT) is a standard treatment option for patients with multiple myeloma. Some patients, however, still experience cancer recurrence (return) following this treatment. Recently, a multi-institutional study published in the Journal of Clinical Oncology reported high response rates to donor lymphocyte infusions in patients with recurrent 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 which 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.
Chemotherapy targets and kills rapidly dividing cells such as cancer cells. Although chemotherapy is effective at killing cancer cells, treatment does not differentiate between cancer cells and healthy cells. High-dose chemotherapy kills more cancer cells than lower dose conventional chemotherapy. Unfortunately, HDC also kills more normal cells, especially the blood producing stem cells in the bone marrow. When these cells reach critically low levels, complications such as anemia, infection and bleeding can occur. The treatment strategy utilizing SCT is an attempt to restore the blood producing stem cells after HDC has reduced them to dangerously low levels. The process of an allogeneic SCT includes the collection of stem cells from a donor that are later infused into the patients after HDC treatment. An important additional benefit of an allogeneic SCT is that the donor’s infused cells may actually attack and kill the patient’s cancer cells. This immune reaction is called the graft-versus myeloma effect.
Even after HDC and allogeneic SCT, some persons will have a recurrence of myeloma. For these persons, additional infusions of healthy immune cells, called lymphocytes, collected from the original stem cell donor may be used to stimulate another attack against the remaining myeloma cells. Researchers from several transplant centers in Europe evaluated 27 patients with multiple myeloma who had a recurrence following treatment with HDC and an allogeneic SCT. All of these patients received infusions of donor lymphocytes after recurrence of the cancer. Over half of the patients experienced a partial or complete disappearance of myeloma following the infusion and the majority of these patients are still alive today. Unfortunately, graft-versus-host disease, a side effect caused by donor cells attacking healthy tissue of the patient, affected over 75% of these patients.
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The results of this study confirm that donor lymphocyte infusions may be beneficial to patients with multiple myeloma who have a recurrence after HDC and allogeneic SCT. Current clinical studies are aimed at increasing response rates and reducing the severity of graft-versus-host disease after a donor lymphocytic infusion. For example, removal of certain lymphocytes prior to infusion may preserve the anti-myeloma effect but decrease the risk of graft-versus-host disease. Persons with recurrent multiple myeloma may wish to talk to their doctor about the risks and benefits of participating in ongoing clinical trials in which donor lymphocyte infusions or other promising new treatments are being studied. (Journal of Clinical Oncology, Vol 18, No 16, pp 3031-3037, 2000)
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