[Non-myeloablative stem cell transplant].

Myeloablation and immunosuppression were considered to be the two major roles of the conditioning regimens for allogeneic stem cell transplantation to facilitate engraftment. It has turned out, however, that immunosuppression is more important and myeloablation is not necessary for engraftment. At the same time, it is considered that the major anti-tumor effect of allogeneic stem cell transplantation depends on the graft-versus-leukemia effect, not on the conditioning regimen itself. In patients with CML who relapsed after allogeneic transplantation, for example, infusion of donor lymphocytes can induce a second complete remission. Non-myeloablative stem cell transplantation (NST) was developed in the late 90s based on these theories. Low-dose, less toxic, so-called "non-myeloablative" preparative regimens have been designed not to eradicate the malignancies, but to provide sufficient immunosuppression to allow donor cells to engraft, while the graft-versus-malignancy effects eradicate the tumor. This strategy permits allogeneic transplantation to be used in patients who are not eligible for conventional, often myeloablative, transplantation because of advanced age or organ dysfunction. Non-myeloablative preparative regimens contain purine analogs, such as fludarabine or cladribine. The NST regimen being used at the National Cancer Center Hospital, Tokyo, Japan, consists of cladribine (0.11 mg/kg x 6 days), busulfan (4 mg/kg x 2 days) and rabbit anti-thymocyte globulin (2.5 mg/kg x 4 days). We enrolled 6 patients in this NST protocol so far: 1 with severe aplastic anemia (sibling-PBSCT), 2 with MDS-RA (1 for sibling-PBSCT and 1 for matched uBMT), 1 with AML-CR2 (matched uBMT), 1 with AML-CR3 (sibling-PBSCT), and 1 with relapsed AML (mismatched related PBSCT). All patients achieved engraftment within 14 days with complete donor chimerism. In addition to leukemias, a graft-versus-malignancy effect was also reported in allogeneic NST of solid tumors, such as renal cell carcinoma and malignant melanoma. The long-term efficacy of NST remains to be determined, and further clinical trials are warranted.