Double versus Single Autologous Stem-Cell Transplantation for Multiple Myeloma: a Region Based Study in 485 Patients from the Nordic Area

Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 23, 2007

Presenter: Björkstrand, Bo
Presenter's Affiliation: Huddinge University Hospital, Sweden
Type of Session: Scientific


Multiple myeloma (MM) is one of the most common indications for high-dose chemotherapy and transplantation in Sweden. Autologous stem cell transplantation (AuSCT) is currently considered the standard of care in young patients with multiple myeloma (MM). Attal et al. (NEJM 1996;335(2):91-7) were the only group to report an overall survival (OS) benefit in a prospective, randomized study comparing double to single transplants in a 399 younger MM patients, demonstrating a doubling of the OS from 42% vs. 21%. Several other randomized studies are in favor of double ("tandem") autologous transplantation, but the long-term benefit remains unclear. This study was initiated in order to assess the long-term effect of double vs. single transplantation in this population.

Materials and Methods

  • Sequential registration trials conducted in Nordic area from 1994-2000, including a regional phase II registration study of double AuSCT
  • Study of 485 previously untreated patients under 60 years of age at diagnosis
  • Patients were all "registration- treated" with either:
    • single AuSCT (Trial NMSG #5/94 and #7/98), N=384
    • double AuSCT (Trial HKTH), N=101
  • All patients received high-dose melphalan (200 mg/m2)
  • Endpoints were event-free survival (EFS) and overall survival (OS)


  • Complete or very good partial response was achieved by 40% of pts in single-transplant group vs. 60% of pts in double-transplant group (p=0.0006)
  • 5-year EFS was 25% in single-transplant group and 44% in double-transplant group (P=0.0014)
  • Estimated 5-year OS rate was 50% in single-transplant group and 50% in double-transplant group (P=0.9).
  • In a multivariate analysis of variables including single vs. double transplantation, beta-2 microglobulin level, age, sex, and disease stage, ONLY beta-2 microglobulin came out significantly for both OS and EFS, respectively (p<0.0001 and p=0.001, respectively).
  • Based on above results, a 1:1 case-control matched comparison was performed between double and single transplantation and did not identify significant differences in OS and EFS.

Author's Conclusions

As compared with single autologous stem-cell transplantation, up front double transplantation did not seem to improve the final outcome among patients with multiple myeloma in the Nordic area.

Clinical/Scientific Implications

In a country like Sweden where socialized medicine prevails, performing routine tandem transplants for the initial treatment of all favorable myeloma patients without clear evidence of its long-term efficacy is not an affordable luxury. In this very important phase II registration study, it does not appear that double transplant offers any statistically significant overall survival advantage over single transplant. Although the five-year event-free survival was better with the double transplant arm, it is not considered to be a compelling enough endpoint to justify this approach universally, and thus single AuSCT remains the standard of care for this geographical region. In the future, a phase III trial in this population may be warranted, as randomization of patients would provide more confident data, and it is not clear in this phase II study how patients were selected to be in either the single or double transplant groups.

See the patient-oriented summary of this study