Long-term follow-up results from a clinical trial show that multiple myeloma patients who underwent two stem cell transplants remained in remission longer and also survived longer than patients who underwent one transplant. These findings are updated results from a previously published study comparing single versus double transplantation.

Multiple myeloma patients are commonly treated with stem cell transplantation. Several studies have shown a survival benefit to having a second transplant a couple of months after the first. However long-term follow-up results are necessary to confirm this.

Patients were recruited for the study between 1992 and 1997, and the initial findings were published in 2001. The current report includes updated results of the trial after following the patients for a median of 13.6 years.

The clinical trial evaluated the outcome of 90 patients (46 newly diagnosed and 44 pre-treated) who were planning on undergoing double (also known as tandem) stem cell transplantation using their own stem cells.

Of the 90 patients, 49 patients actually underwent the second transplantation.

Stem cells for the first transplant were collected prior to a preparative conditioning regimen of high-dose melphalan ^[1] (Alkeran) and then transplanted back after the melphalan treatment.

Stem cells for a second transplant are often collected at the same time as the stem cells for the first transplant, but some myeloma cells remain in the bone marrow and can be collected along with the stem cells. In an attempt to increase the efficacy of the regimen, this study collected stem cells for the second transplant several months after the first transplant.

Patients who were eligible for the second transplant received conditioning therapy with a combination of busulfan ^[2] and cyclophosphamide ^[3] (Cytoxan) and then received transplanted cells that were collected after their first transplant.

At the time of the trial, novel agents, such as thalidomide ^[4] (Thalomid), Revlimid ^[5] (lenalidomide), and Velcade ^[6] (bortezomib), had not yet been introduced for the treatment of myeloma.

In both the original and updated reports, patients undergoing tandem transplantation experienced a median overall survival of 84 months. However, long-term follow-up showed that overall survival of patients who underwent single transplantation decreased from 49 months in the initial analysis to 44 months in the updated report.

Initially, the data showed that patients receiving tandem transplants were likely to have better survival than patients receiving a single transplant. However, only in the follow-up results was the difference between the two groups significant, demonstrating the importance of long-term follow-up of clinical trial participants.

Patients who received tandem transplants also achieved significantly better 10-year overall and event-free survival than patients who received a single transplant (34 percent versus 18 percent for overall survival, and 18 percent versus 0 percent for event-free survival). This data was similar to previous studies comparing single and double transplants.

The researchers noted that at the time of the follow-up analysis, 12 percent of patients who underwent tandem transplantation were still in remission. They also noted a “plateau” in remission rates after 130 months (almost 11 years), meaning that patients who were still in remission at that time were much less likely to relapse later. They attributed this long-term remission to the high-intensity of the regimen, not the use of stem cells collected after the first transplant.

The researchers concluded that the new long-term follow-up data confirm the promising results published in the original report. Additionally, the long-term results show that tandem transplantation is superior to single transplantation.

In their evaluation of the updated follow-up data, the researchers cautioned that it is important to consider a possible selection bias in the trial. Patients with a good prognosis may have been more likely to undergo a second transplant. The primary reasons for not undergoing the second transplant were insufficient stem cell harvest (23 percent, likely due to harvesting after high-dose melphalan), toxicity of previous treatment (9 percent), and progressive disease (8 percent).

For more information, please read the follow-up report in the Journal of Clinical Oncology ^[7] (pdf) or the initial results published in Bone Marrow Transplantation ^[8].