The role of stem cell transplantation in multiple myeloma

High-dose therapy with autologous stem cell transplantation (ASCT) has been extensively used in the past 15 years in multiple myeloma. The IFM 90 trial has shown that autologous bone marrow transplantation (BMT) is superior to conventional chemotherapy in terms of response rate, event free survival, overall survival. Several other randomized studies confirm that ASCT yields superior complete remission and event free survival rates. However, the benefit for overall survival is not always significant because some patients may receive high-dose therapy at the time of relapse. While ASCT appears to be the treatment of choice for younger patients, a number of questions have been addressed in the past few years (optimal conditioning regimen, best source of stem cells, impact of tandem autotransplants, role of maintenance therapy, results of transplantation in patients over 65 years of age or with renal failure). These issues are addressed in this review. Analysis of large cohorts of patients indicate that a low beta2 microglobulin level and the absence of chromosome 13 abnormalities are associated with a better outcome. However patients with a high-beta2 microglobulin level and chromosome 13 abnormalities, the prognosis is poor even after tandem transplantations. Allogeneic BMT is offered to a minority of younger patients with an HLA identical sibling. Initial series have shown a high-toxic death rate and no survival advantage compared to ASCT. However, allogeneic BMT is possibly the only curative therapy. Reports of CR achieved after infusion of donor lymphoid cells in patients relapsing after allogeneic BMT support the concept of graft versus myeloma effect. Therefore, the objectives of current studies is to reduce transplant related mortality by using earlier BMT, better selection of patients, better graft-versus host prophylaxis or non myeloablative conditioning regimens.