Randomized controlled trials of autologous hematopoietic stem cell transplantation for autoimmune diseases: The evolution from myeloablative to lymphoablative transplant regimens

While autologous HSCT appears to induce remissions and improve quality of life in the majority of patients, it remains unclear whether either myeloablative or lymphoablative autologous HSCT can cure autoimmune disorders, and randomized controlled trials are needed to confirm the benefit and cost-effectiveness of this therapy. There are currently 2 disparate philosophical approaches to the design of these trials. One approach is to apply aggressive malignancy-specific myeloablative regimens. Although more intensive lymphoablative regimens could be designed, since cancer-specific myeloablative regimens are more intensive than currently utilized lymphoablative regimens, myeloablative regimens may result in longer duration of disease remission. The other philosophical approach is to use lymphoablative regimens that are disease specific and nonmyeloablative (i.e., do not irreversibly damage the hematopoietic stem cell compartment), maximize drugs already used to treat each disease, and avoid agents in the regimen that could cause further damage to already disease-injured organs. It appears that lymphoablative regimens are safer than myeloablative regimens, and it appears that even if relapse occurs, durable long-term remission may be achieved with conventional treatment to which the patient's disease was previously refractory. If considered on a disease-specific basis, the high disease-related mortality of SSc could justify the higher treatment-related mortality associated with a myeloablative regimen. However, since radiation is already considered a relative contraindication for SSc and radiation-induced and SSc-related microvascular compartment injuries are similar, and because TBI is associated with late myelodysplasia, leukemia, and lymphomas, some investigators have voiced concern over use of a TBI-based myeloablative regimen to treat SSc (19,59). The controversy that surrounds the competing visions of lymphoablative versus myeloablative autologous HSCT regimens for autoimmune disease has yet to be resolved. Further experience will likely indicate the superiority of one of these approaches when both safety and efficacy are considered. Since both lymphoablative and myeloablative protocols are being offered for a select group of severely ill patients with autoimmune disorders refractory to conventional therapy, subspecialists who refer patients for such therapy should be aware of the emerging body of literature that at the very least suggests that lymphoablative regimens will be associated with less morbidity and mortality. Sharing of such information is crucial if patients are to provide consent that is truly informed.