Minitransplants: allogeneic stem cell transplantation with reduced toxicity

Allogeneic hematopoietic stem cell transplantation (HSCT) is used for the treatment of selected hematological malignancies. Its curative potential is based on two very different mechanisms, involving the conditioning regimen and the graft-versus-host reactions, respectively. The high-dose chemo-radiotherapy conditioning regimen is aimed at destroying tumor cells, ablating the host immune system (to prevent rejection) and eliminating the host bone marrow (to "make space" for donor stem cells). However, the definitive eradication of tumor cells is also largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger (< 55 years) and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols based on a two step approach: first the use of immunosuppressive (but nonmyeloablative) conditioning regimens providing sufficient immunosuppression to achieve engraftment of allogeneic hematopoietic stem cells and, in a second step, destruction of malignant cells by the GVL effect. These transplants are called nonmyeloablative HSCT or reduced-conditioning HSCT or minitransplants. Preliminary results show that minitransplants are feasible with a relatively low transplant-related mortality (TRM) even in patients up to 70 years. In addition, strong anti-tumor responses are observed in several hematological malignancies as well as in some patients with renal cell carcinoma. As the benefits of minitransplants over alternative forms of treatment remain to be demonstrated, this strategy should be restricted to patients included in clinical trials.