Improved Treatment of AL Amyloidosis

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The summary below is from the full report titled "High-Dose Melphalan and Autologous Stem-Cell Transplantation in Patients with AL Amyloidosis: An 8-Year Study." It is in the 20 January 2004 issue of Annals of Internal Medicine (volume 140, pages 85-93). The authors are M. Skinner, V. Sanchorawala, D.C. Seldin, L.M. Dember, R.H. Falk, J.L. Berk, J.J. Anderson, C. O'Hara, K.T. Finn, C.A. Libbey, J. Wiesman, K. Quillen, N. Swan, and D.G. Wright.

What is the problem and what is known about it so far?

Bone marrow consists of several kinds of cells. These cells manufacture many chemicals known as proteins. One kind of bone marrow cell (plasma cell) makes a protein called amyloid that is produced in different forms. One form is lighter in weight than others. Abnormal plasma cells may produce too much light amyloid, which results in a disease called AL amyloidosis. This protein is then deposited in different organs, causing progressive disability and death. Without treatment, patients usually die within about a year. If amyloid deposits affect the heart, death occurs more rapidly (in about 5 months). Treatment with a drug called melphalan destroys abnormal plasma cells and, when given by mouth, can lengthen survival. A promising new approach to treatment involves giving high-dose melphalan intravenously. However, this approach also kills normal bone marrow cells, which must then be replaced. This is done by collecting a special type of cell (known as stem cells) from the patient's bone marrow or blood before melphalan is administered and then giving them back to the patient (a process known as autologous stem-cell transplantation) after melphalan administration. Stem cells can regenerate normal bone marrow cells that have been lost during melphalan treatment.

Why did the researchers do this particular study?

To determine whether high-dose melphalan treatment and autologous stem-cell transplantation could improve survival in AL amyloidosis.

Who was studied?

701 consecutive patients with AL amyloidosis who took part in 6 different studies over 8 years.

How was the study done?

The researchers reviewed the results of 312 patients with AL amyloidosis who were treated with high-dose melphalan and stem-cell transplantation and compared them with results from other patients who were not eligible for this treatment. They looked for evidence of persistent AL amyloidosis after treatment and at how long each patient survived. They also determined how well different organs were working.

What did the researchers find?

Half of all patients who received treatment survived for more than 4.5 years. Of 137 patients with heart involvement, half were alive after 1.5 years. Of those without heart involvement, half were alive after 6.5 years. Forty percent of treated patients had no evidence of AL amyloidosis after treatment (complete remission). Of those who remained in complete remission 1 year after treatment, 8% had relapses within 2 years but none had relapses after 2 years. Half of the patients who were not eligible for the treatment died within 4 months.

What were the limitations of the study?

Patients were collected from 6 different studies conducted over 6 years. Each study had somewhat different methods and chose different types of patients. Patients who were excluded from treatment (the comparison group) were older and sicker than those in the treatment group.

What are the implications of the study?

Treatment with high-dose melphalan and stem-cell transplantation can improve survival, even in patients with heart involvement.