Immune reconstitution after T-cell replete HLA-haploidentical transplantation

Impaired immune reconstitution has been one of the perceived limitations of alternative donor transplantation. However, modern transplantation platforms such as HLA-haploidentical transplantation with either post-transplantation cyclophosphamide or with anti-thymocyte globulin combined with intense immunosuppression may be associated with robust immune recovery as inferred by low rate of infectious mortality and post-transplantation lymphoproliferative disease. Here, we review the data on immune reconstitution including individual cell subsets, the effect of reconstitution on outcomes, and comparative studies using these commonly utilized T-cell replete HLA-haploidentical platforms. We find robust recovery of neutrophils, natural killer cells, CD8⁺ T-cells, and B-cells, with delayed CD4⁺ T-cell recovery comparable to that after HLA-matched transplantation. In addition, while viral reactivations and infections appear more common after HLA-haploidentical when compared with HLA-matched transplantation, infectious mortality remains low likely due to modern cytomegalovirus monitoring, preemptive treatment, as well as relative frequency of nonlethal viral infections like polyomavirus hominis 1 (BK virus). Higher graft cell doses also appear to be associated with faster recovery without concomitant increases in lethal graft-vs-host disease. Finally, despite rapid numerical return of natural killer cells post-transplant, phenotypically they retain immaturity markers till day 180 or more after transplantation, which suggests an avenue for future research to improve outcomes further.