How antithymocyte globulin,a polyclonal soup of the past century,when carefully dosed,has become crucial for hematopoietic stem cell transplantation with haplo-identical donors in the 21st century

抗胸腺细胞球蛋白如何在21世纪的单倍型供者造血干细胞移植中发挥重要作用

Hematopoeitic stem cell transplantation(HSCT)using a haploidentical family donor(HAPLO)was long thought to be non-feasible,essentially because of HLA incompatibility leading to graft rejection,severe acute(aGVH)and chronic(cGVH)graft versus host disease(GVH),severe infections and unacceptable nonrelapse mortality(NRM).The group in Perugia in the last decade of the past century[1],was the first to be successful by initiating a positive selection of CD34+cells from peripheral blood stem cell(PBSC)collections,providing T cell depleted grafts with very high doses of CD34+cells to be infused.When combined with intensive conditioning regimen and profound immunosuppression,the Perugia group obtained the first demonstration of feasibility and efficacy.They later improved their results in acute myeloid leukemia(AML)by showing that a mismatch for natural killer(NK)cells in the killer-cell immunoglobulin-like receptor(KIR)-human leukocyte-antigen class I(HLA1)donor to recipient direction[2]decreased considerably the relapse incidence(RI).Unfortunately this approach was associated with severe infections,a high NRM and in addition was cumbersome and difficult to reproduce in other non-expert centers.