IFM94.

Methods	Central randomisation at diagnosis Multicentre (N=45) RCT assessing superiority of TASCT 2x2 factorial design: additional randomisation between bone marrow and peripheral blood stem cells
Participants	TASCT N=200, SASCT N=199; (long‐term follow‐up: TASCT N=203; SASCT N=199) age < 60 years Previously untreated patients with MM Salmon‐Durie stage I (with bone lesion), II‐III (Baseline characteristics Table 2)
Interventions	"Dose‐escalating" TASCT regimen compared to SASCT (conditioning melphalan + TBI 8 Gy) ‐ both either with bone marrow or peripheral blood stem cells (Treatment regimen Table 3)
Outcomes	OS, EFS, treatment‐ and transplantation‐related mortality in ITT population (Definition of endpoints Table 4; Table 5)
Period and Location	Oct 94 – Mar 97 in France and Belgium
Sample size calculation	Improvement of CR%
ITT analysis (n of drop‐outs)	Yes (NR)
Notes	Journal publication (peer review) Long‐term follow‐up data for OS and EFS available No clinically relevant interaction of two randomisations Dose‐escalating" TASCT regimen not comparable to current treatment approaches (dose of first ASCT lower than only ASCT in SASCT arm) Low compliance (75%) with second ASCT in TASCT arm Potential confounding subsequent salvage treatment (inferior post‐relapse survival in TASCT group)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Central
Allocation concealment (selection bias)	Low risk	Central
Blinding (performance bias and detection bias) All outcomes	High risk	Unavoidable in view of obvious difference in treatment plan
Other bias	High risk	See Table 6 and Figure 2