Page 272 - 2021_02-Haematologica-web

Letters to the Editor
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Figure 1. Immune recovery after allogeneic hematopoietic stem cell transplantation. (A) CD4+ lymphocytes, (B) CD8+ lymphocytes, (C) natural killer cells, (D) B-lymphocytes. Dashed lines represent the upper and lower limits of reference values.
alleles in 92% of patients after dUCBT. These alloreactive CD4+ T cells showed activity towards patient-derived leukemic cells, especially when the mismatch was shared between recipient and the ‘loser’ cord blood unit.3,4 In the present study, we set out to explore HLA-class II-specific CD4+ T-cell alloreactivity after haploidentical HSCT. Here we show the presence of such T cells for 36% of the test- ed alleles, which is much lower than the 92% detected after dUCBT, supporting our hypothesis that CD4+ T-cell alloreactivity may be less predominant after haploidenti- cal HSCT.3
Current standard regimens of GvHD prophylaxis include the combination of a calcineurin inhibitor, cyclosporine, or tacrolimus, and either mycophenolate mofetil, or sirolimus, while prophylaxis in haploidentical HSCT consists of additional high-dose PT-Cy.6 Mycophenolate mofetil inhibits T-cell proliferation and adhesion, which hamper T-lymphocytic responses to allogeneic cells.7 Calcineurin inhibitors specifically inhibit intracellular signals responsible for T-cell activation after antigen binding, while PT-Cy induces apoptosis in allore- active donor T cells after their activation and entry into the proliferative phase.8,9 Thus, it might further reduce the proliferation of early reconstituting alloreactive T cells with antileukemic potential. In addition, NK-cell recovery might also be compromised. Russo et al. recent- ly studied NK-cell recovery and alloreactivity after hap- loidentical HSCT with PT-Cy.10 In that study, NK-cell pro- liferation was completely abrogated by day 8 after PT-Cy, suggesting selective elimination of cycling NK cells.
Importantly, donor NK cells harvested from patients at days 15 and 30 after haploidentical HSCT had a less mature phenotype. In addition these immature NK cells displayed less alloreactivity and an impaired antileukemic potential.
Overall, haploidentical HSCT with PT-Cy is character- ized by a delayed early immune reconstitution, especially of CD4+ T cells, in comparison to the reconstitution fol- lowing transplantation with donor cells from other sources, reaching normal levels after roughly 1 year.11 Antigen-presenting cells play a central role in activating T cells and initiating immune responses. Several studies have shown that recovery of dendritic cells is also delayed after haploidentical HSCT and normal values are gradually achieved 1 year after transplantation.11,12 Delayed recovery of such antigen-presenting cells may lead to less presentation of recipient class II antigens and contribute to the relatively low numbers of alloreactive CD4+ T cells found in this study. A recent study explored dendritic cell recovery after dUCBT and matched sibling donor transplantation.13 Interestingly, umbilical cord blood recipients had better dendritic cell reconstitution in comparison to recipients of grafts from matched related donors, with normal values being reached at day 100 after transplantation. In addition, better dendritic cell recovery in the cord blood setting was associated with fewer relapses. Moreover, circulating class II-expressing cells after infusion of both cord blood units in a dUCBT might contribute to presenting mismatched HLA-class II to CD4+ T cells. Strong expression and/or a high number
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haematologica | 2021; 106(2)