Hematopoietic stem cell transplantation with autologous cells (ASCT) is the therapy of choice in most patients with multiple myeloma up to the age of about 65-70 years of age.Transplantation with allogeneic cells (AlloSCT) is controversial, but may have curative potential.Our aim has been to compare AlloSCT with ASCT in a prospective trial after long term follow-up.In an EBMT (European Group for Blood and Marrow Transplantation) study 357 patients were included, and median follow-up was 61 months.Based on the availability of an HLA identical sibling donor 108 patients were allocated to AlloSCT (91 actually received the allotransplant according to protocol) and 249 to ASCT with the options to perform either single or tandem ASCT.After induction with the VAD combination (vincristine + doxorubicine (Adriamycin) +dexamethasone) AlloSCT patients received reduced intensity conditioning with irradiation-2GY + fludarabine (RIC) followed by the allotransplant and ASCT patients received melphalan 200 mg2/m followed by the autotransplant.On an intention to treat analysis PFS and OS were significantly superior at 60 months in the RICAlloSCT group, 35% versus 18% and 65% versus 58% respectively.Patients that received the RICAlloSCT according to protocol still had superior outcome as compared to tandem ASCT.The outcome pattern was similar in patients with or without the chromosome 13q deletion.Five other similar prospective studies comparing RICAlloSCT and ASCT based on the availability of an identical sibling donor have recently been published.The IFM (Garban 2006) included only "high risk" patients (serum beta-2 microglobulin > 3 mg/l and deletion of chromosome 13)-65 were allocated to tandem ASCT-RICAlloSCT and 219 to tandem ASCT.RIC consisted of busulfan + fludarabine and high dose ATG.No significant difference in outcome between the groups was found.The Italian group (Bruno 2007) showed superior PFS and OS for patients who received ASCT-RICAlloSCT, 245 patients were included at diagnosis.HLA typing was performed in 162 patients and 80 of these had an HLA-identical sibling donor and 82 had none.Whether analyzed as an intention to treat or on the actual treatment, there was a significant advantage for ASCT-RICAlloSCT after a follow-up of 84 month.The PETHEMA group (Rosinol 2008) included only patients who did not enter CR or near CR at the first auto.110 patients had a second transplant, 25 of them RICAlloSCT.There was no significant difference in outcome, but a trend for better PFS with ASCT-RICAlloSCT The HOVON group (Lokhorst 2008) used TBI 2 GY for RICAlloSCT conditioning.Out of 126 patients that had a donor 101 received RICAlloSCT and out of 141 without 115 received ASCT.At an interim analysis there was no significant difference in outcome.The collaborative BMT CTN 0102 (USA) study (Krishnan 2010) included 710 patients (484 tandems ASCT and 226 tandem ASCT-RICAlloSCT).RIC conditioning was TBI 2 GY.At 3 years there was no significant difference in PFS or OS.Longer follow up was considered necessary for conclusions.ASCT is still the preferred treatment modality for multiple myeloma in patients younger than 65-70 years.Combinations with new drugs have improved results.ASCT combination with RIC AlloSCT is still controversial.Differences in results in the six studies may be due to differences in immunosuppression (ATG in the study by Garban), conditioning, inclusion criteria and follow-up time.Prospective RIC AlloSCT studies only rarely use new drugs for induction, in the conditioning or as maintenance.Further studies should include these drugs in AlloSCT.Hopefully such approaches will lead to the cure of at least a fraction of treated patients.