One of the most frequent questions that I get asked by multiple myeloma patients is: What is the current role of stem cell transplantation in myeloma therapy?

As the conversation continues, several pertinent questions arise: Should I get a transplant? Am I too old for a transplant? Is it better to do one now, or can I wait? One or two? Two back to back, or one now and one later? And so on…

Myeloma is the number one use of autologous stem cell transplantation, which involves the use of a patient's own stem cells, in the United States. And with good reason.

Two randomized trials showed a clear improvement in survival with transplantation. All things considered, on average, myeloma patients derived an extra one- to two-year prolongation in survival on top of what they would have achieved without autologous transplantation. As with all studies, these numbers are averages, and some patients benefit a lot more, and some a lot less.

Today, autologous transplantation for myeloma is extremely safe, and in major centers approximately 30 percent to 40 percent of transplants can be done entirely as an outpatient. In fact, some patients feel that the initial therapy may have been harder on them than the transplant.

Who should consider a transplant? In Europe, the role of transplantation is largely restricted to patients less than 65 years of age.  In the U.S., there is no strict age limit, and Medicare covers transplantation up to age 78. We consider physiologic age, the overall physical and medical condition of the patient, when deciding whether or not the procedure can be performed safely.

Should transplantation be done early in the newly diagnosed stage, or can it be delayed until the initial therapy fails? This is controversial. We usually prefer early autologous transplantation following three to four months of initial therapy, for a variety of reasons. However, as long as stem cells can be collected and stored for future use, it may be possible to delay transplantation until the first relapse.

Three randomized trials in the days before new agents arrived studied whether transplantation should be done as part of initial therapy or delayed until relapse. None of these trials showed a survival benefit with early transplantation. Time without therapy was longer with transplantation in one trial, but that may not be a factor if post-transplant maintenance therapy is contemplated.

There is one ongoing trial led by the Dana Farber Cancer Institute and the French IFM group that is currently examining early versus delayed transplant.

At present, for patients who do not have high-risk cytogenetic features, we take patient preference and quality of life into consideration when deciding early versus delayed transplantation. Roughly half of the transplant-eligible patients at Mayo Clinic choose to delay transplantation.

Should patients get one or two transplants? This is also a controversial topic. In randomized trials, two transplants appear to prolong survival compared with one, but the benefit appears to be largely restricted to patients not achieving a very good partial response or better with the first transplant.

Some investigators continue to maintain that two transplants done back to back early in the disease course (tandem transplantation) offers the best chance at long-term survival. Others reserve a second transplant for selected patients.

We usually collect enough stem cells for two transplants, proceed with the first, and decide on the second based on the response to the first. If a second is not deemed necessary, the stored stem cells can be preserved indefinitely for future use.

What does the future hold? With current initial therapy regimens, we are achieving promising results, and trials are ongoing to determine the current role of transplantation.

For now, I feel that autologous transplantation remains a valuable option for eligible patients. Myeloma physicians may have differing opinions on the appropriate timing (early versus delayed) or the number (one or two), but most would agree that it is an important option that cannot be ignored.

Dr. S. Vincent Rajkumar is a professor of medicine at the Mayo Clinic in Rochester, Minnesota. His research focuses on clinical, epidemiological, and laboratory research for myeloma and related disorders.