The purpose of this study is to determine whether autologous transplantation (using the patient's own stem cells from the blood), followed by non-myeloablative (i.e. less intense) allogeneic transplantation (where the blood stem cells from a sibling donor are used for the transplantation) improves the outcome in patients with newly diagnosed multiple myeloma.

This trial includes a natural (no available HLA-identical sibling donor) control arm. Patients with newly diagnosed multiple myeloma without a sibling are initially treated with conventional chemotherapy followed by conventional single or double autologous transplant (PBSCT). Data from this group is used as part of the control group.

Eligible patients with one or more sibling are offered to participate in the main trial arm. Those who decline are asked to consider taking part in the control group (autograft only).

Patients consenting to participate in the main study first receive the PBSCT, followed by the HLA-matched non-myeloablative allograft (matched for HLA -A, -B, -C, -DRB1).

All study patients receive four to six cycles of VAD (or alternative regimens specified in protocol) before PBSCT as first line treatment. Study entry starts at the time of starting conditioning for autologous transplantation. The search for an identical sibling donor begins as soon as the patient has consented to participate in the study.

The allograft is performed when the patient has restored their marrow function but no earlier than 3 months following PBSCT.

The aim is to demonstrate a difference in outcome (progression free survival, transplant related mortality, relapse rate, and survival).

Inclusion Criteria:

• Newly diagnosed Stage-II and III multiple myeloma (According to Durie and Salmon classification)
• Age under 70 years
• Life expectancy over 3 months
• Patients must be able to give informed consent

Exclusion Criteria:

• Serious concomitant medical disease which would limit life span or the ability to tolerate chemotherapy
• Severe cardiac failure (ejection fraction <40%)
• Impairment of renal function at diagnosis is not per se reason for exclusion but patients with severe impaired renal function (GFR <50 ml/min) after initial VAD (or VAD like) induction treatment are excluded
• Severe impairment of liver function (bilirubin >2 times upper limit of normal)
• Pregnant or lactating women
• Other major organ system dysfunction (GI, neurological, psychiatric dysfunction) that impairs tolerance of therapy or prolong hematological recovery