Long-term survival after HLA-haploidentical SCT from noninherited maternal antigen-mismatched family donors: impact of chronic GVHD.

摘要

Allo-SCT from an HLA-haploidentical family donor has been the treatment of choice in patients with high-risk hematologic malignancies, who are expected to have a better prognosis with SCT but lack immediate access to a conventional stem cell source.1-2 With intent to minimize the risk of severe GVHD, most haploidentical SCT protocols employ ex vivo or in vivo T-cell depletion, albeit at the expense of an increased risk of infection or relapse as a result of poor post-transplant immune reconstitution. To develop an alternative strategy to perform haploidentical SCT that confers improved immune recovery and acceptable risk of GVHD, we have explored the feasibility of T-cell-replete SCT from family donors mismatched for noninherited maternal HLA antigens (NIMA); NIMA-mismatched donor selection is based on the hypothesis that the detection of long-term maternal or fetal microchimer-ism in the donor's peripheral circulation is associated with immunological hyporesponsiveness against NIMA (in the case of NIMA mismatch in the graft-vs-host direction) or against inherited paternal HLA antigens (IPA) (in the case of NIMA mismatch in the host-vs-graft direction). According to this scenario, we and other groups showed that T-cell-replete HLA-haploidentical SCT from a NIMA-mismatched family donor is feasible in selected patients with poor-risk hematologic malignancies.3-4 However, late complications and long-term outcomes in patients undergoing such transplantations have been so far largely unknown. Therefore, we retrospectively studied the severity of chronic GVHD, requirement for immunosupressive treatment, and status of primary disease in long-term survivors who received T-cell-replete NIMA-mismatched haploidentical SCT.