The allogeneic dilemma

The place of allogeneic SCT in the management of multiple myeloma remains controversial. Although it may induce long-term clinical and molecular remissions, the very high transplant-related toxicity after a myeloablative preparative regimen has limited its role to younger patients as first-line treatment option. Even with this limited indication, toxic death rate related to infections and GVHD is considered too high and this strategy has been almost abandoned. Reduced intensity conditioning (RIC) regimens look promising, as the transplant-related mortality is low even with matched unrelated donors and can be considered for older patients up to the age of 65 years. However when used in patients with a high tumor burden or with chemo-resistant disease, the immunologic effect of the graft is not sufficient to avoid relapses. Therefore, RIC allotransplantation is currently used after tumor mass reduction with high-dose therapy followed by autologous SCT. A recently published Italian study shows that this strategy induces better event-free survival than double autologous SCT due to a reduced relapse rate. The questions raised by this encouraging result are discussed in this paper.