Bone marrow transplantation

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Fosamax), risedronate (trade name: Actonel), and etidronate (trade name: Didronel).

blood tests See Appendix II.

bone marrow transplantation An aggressive therapy undergoing evaluation for a range of autoimmune disorders. Bone marrow transplantation (BMT) involves high-dose immunosuppressive treatment followed by bone marrow replacement. BMT was developed as a treatment for several types of cancer. Virtually all types of chemotherapy for cancer suppress the bone marrow, which makes red and white blood cells and platelets. The theory behind BMT was that much higher doses of anticancer drugs could be used to eradicate cancer throughout the body, including the bone marrow, if physicians did not have to avoid suppressing the bone marrow. Isolated reports that autoimmune disease improved in patients who received a bone marrow transplant for cancer and studies in animal models showing benefits from BMT, have led to widespread interest in it as a potential treatment for autoimmune disease.

Autologous and allogeneic transplants There are two major types of BMT—autologous and allo-geneic. In autologous transplantation, patients receive their own marrow or stem cells. In allo-geneic transplantation, they receive the bone marrow from a donor closely matched for tissue type (see hla). The complications and mortality are much lower with autologous transplantation because rejection is not a problem. Virtually all the transplants performed for autoimmune disease have been autologous stem cell transplants.

Autologous stem cell transplants A stem cell transplant involves three phases.

1. The patient receives cyclophosphamide and granulocyte colony stimulating factor (G-CSF) to mobilize stem cells from the bone marrow. The cells are harvested by drawing the patient's blood out of a vein, separating the stem cells, and returning the blood to the patient. The stem cells are stored for later use.

2. High doses of chemotherapy that are toxic to the bone marrow are administered. This is sometimes called the conditioning regimen. There are several different conditioning regimens, but most are based on high-dose cyclophosphamide. The treatment causes severe bone marrow suppression, and white blood cell and platelet counts decrease dramatically. 3. The stem cells are injected back into the patient through a vein and repopulate the bone marrow. The stem cells take about two weeks to establish themselves and differentiate into cells that produce white blood cells and platelets. During these two weeks, the patient has almost no white blood cell and platelets, and the risk of infection and bleeding is high. Patients who receive their own stem cells do not need immunosuppression because they will not reject their own cells.

As a Treatment for Autoimmune Disease More than 500 patients have received high-dose chemotherapy with stem cell rescue for a range of autoimmune diseases. There are no controlled clinical trials, so knowing how this treatment compares with more standard ones is difficult. The effectiveness of BMT may have been underestimated because patients who received a bone marrow transplant were usually selected because they had not responded to standard treatments.

BMT has been tried in patients with rheumatoid

ARTHRITIS (RA), SYSTEMIC LUPUS ERYTHEMATOSUS (SLE), SCLERODERMA, and JUVENILE ARTHRITIS. Responses to treatment have been variable, and physicians are not yet certain what the exact response rate will be for each disease. Approximately a third of patients have an impressive clinical response, another third a moderate response, and the final third no response. The treatment does not cure autoimmune disease. Even patients who respond very well initially often relapse after months or sometimes a few years. Many centers are performing research to define which patients are likely to respond to BMT. There have also been reports of patients with SLE responding to high doses of cyclophosphamide without stem cell transplantation.

BMT is expensive and can have severe side effects. The risk of death varies from center to center. However, it is approximately 1-2 percent for patients with RA but much higher, approximately 10 percent, for those SLE and scleroderma. The long-term complications of the treatment may

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