In myeloma patients younger than age 60, two courses of intensive chemotherapy and blood-forming stem cell transplantation can be better than one. According to a French study, twice as many patients who got double transplants were alive after 7 years, compared to single-transplant patients.

The study, reported in the New England Journal of Medicine (Vol. 349, No. 26: 2495-2502), may help define the role of double stem cell transplants in the treatment of multiple myeloma, a cancer of cells of the bone marrow that is diagnosed in about 15,000 Americans yearly. Because this is a disease of older people – two-thirds of patients are older than 65 – the number of people affected is slowly increasing as the population ages. According to the National Cancer Institute, only about 30% of patients survive 5 years.

Unfortunately, modern chemotherapy drugs have had little impact on this disease. The most widely used and effective drug, melphalan, has been available since the 1960s. With no better drugs available, doctors began using extremely high doses of melphalan to treat myeloma patients.

But melphalan destroys blood-forming cells in the bone marrow and is fatal at high doses. To overcome this, patients are "rescued" by the infusion of their own blood-forming stem cells, which are harvested from the bone marrow or blood before the treatment. This process is known as autologous stem cell transplantation.

Stem cell transplant is used more commonly against myeloma than any other disease, according to Edward Stadtmauer, MD, a specialist in transplantation from the University of Pennsylvania who wrote an editorial accompanying the study. Myeloma patients who get this treatment tend to respond better and relapse later than patients who receive only chemotherapy.

Preliminary studies from several cancer centers suggested that patients might do even better if they received a second stem cell transplant after recovering from the first. To prove this, the French researchers undertook a head-to-head comparison of single and double transplants. Their results establish that the double transplant is better for some patients.

The researchers treated 399 patients who had multiple myeloma. All were younger than age 60 and had advanced disease, but had never received chemotherapy. Except for the myeloma, they were in good health.

Half the patients received a single course of intensive treatment with high-dose melphalan, low doses of radiation, and a transplant of blood-forming stem cells that were taken from them before the treatment.

The second group had the same treatment twice, although they received radiation only with the second transplant.

Patients who received the two courses of treatment had a 42% survival after 7 years, compared with 21% for the group receiving one course of treatment.

Not everyone needs the double procedure, however, researchers found. For many patients, the myeloma mostly disappeared after the first transplant. That group of patients lived just as long whether or not they had a second transplant.

The patients who seemed to benefit the most were those who had a poor response after the first transplant. Such patients may be the best candidates for this treatment, Stadtmauer suggests.

In spite of these good results, the French researchers caution that many questions about this treatment remain. Most of their patients relapsed eventually, and it isn't clear that any will be cured. Also, it isn't clear that people over age 60 – thus, the majority of myeloma patients -- would benefit from double stem cell transplants.

Nevertheless, they and Stadtmauer are optimistic that this treatment and others could improve the outlook for people with multiple myeloma.

Eliminating radiation from the stem cell transplant process might help patients avoid some side effects, the French researchers say. Giving higher doses of melphalan, or waiting to give the second transplant until the myeloma has progressed may also be options.

New treatments also are on the horizon. Drugs such as thalidomide and bortezomib have been effective in treating myeloma, and studies are under way to determine how they can best be used.

"The year 2004 will be an encouraging time for patients with myeloma, but the best is yet to come," Stadtmauer wrote.