TY - JOUR
T1 - Immune reconstitution after T-cell replete HLA-haploidentical transplantation
AU - McCurdy, Shannon R.
AU - Luznik, Leo
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - Haploidentical
KW - Immune reconstitution
KW - Myeloablative
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U2 - 10.1053/j.seminhematol.2019.03.005
DO - 10.1053/j.seminhematol.2019.03.005
M3 - Review article
C2 - 31202434
AN - SCOPUS:85065123691
SN - 0037-1963
VL - 56
SP - 221
EP - 226
JO - Seminars in Hematology
JF - Seminars in Hematology
IS - 3
ER -