Next generation HLA-haploidentical HSCT

作者：Martelli M F^*; Ianni M D; Ruggeri L; Falzetti F; Carotti A; Reisner Y; Velardi A

来源：Bone Marrow Transplantation, 2015, 50(S2): S63-S66.

DOI：10.1038/bmt.2015.98

Relapse is still the major cause of failure of allogeneic stem cell transplantation in high-risk acute leukemia patients. Indeed, whoever the donor and whatever the transplantation strategy, post-transplant relapse rates are similar to 30%, which is hardly satisfactory. The present phase 2 study analyzed the impact of adoptive immunotherapy with naturally occurring FoxP3+ T-regulatory cells (2 x 10(6) per kg) and conventional T lymphocytes (1 x 10(6) per kg) on prevention of GvHD and leukemia relapse in 43 high-risk adults undergoing full-haplotype mismatched transplantation without any post-transplant immunosuppression. Ninety-five percent of patients achieved full-donor type engraftment. Only 6/41 patients (15%) developed >= grade II acute GvHD. Specific CD4(+) and CD8(+) for opportunistic pathogens emerged significantly earlier than after standard T-cell-depleted haplo-transplantation. The probability of disease-free survival was 0.56. At a median follow-up of 46 months (range 18-65 months), only 2/41 evaluable patients have relapsed. The cumulative incidence of relapse was significantly lower than in historical controls (0.05 vs 0.21; P = 0.03). These results demonstrate that the immunosuppressive potential of Tregs can be used to suppress GvHD without loss of the benefits of GvL activity. Humanized murine models provided insights into the mechanisms underlying separation of GvL from GvHD.

• 出版日期2015-6