Improved survival rate in T-cell depleted haploidentical hematopoietic cell transplantation over the last 15 years at a single institution

Abstract

T-cell depletion of an HLA-haploidentical (haplo) graft is often used to reduce the risk of graftversus-host disease (GVHD), but the lack of donor T cells in the infused product may lead to graft failure, slow T-cell reconstitution, infections, and relapse. More selective T-cell depletion targeting CD45RA can effectively deplete naïve T cells but preserve large numbers of memory T cells leading to robust engraftment of diverse T-cell populations and reduction of viremia in the early post-transplant period. Herein, we report the outcome of 143 pediatric and young adult hematologic malignancy patients receiving a first allogeneic hematopoietic cell transplantation (HCT) on 6 consecutive ex vivo T-cell depleted haploHCT protocols over the past 15 years at a single institution-including the first 50 patients on an active CD45RA-depleted haploHCT study in which patients also received NK-cells and pharmacological GvHD prophylaxis post transplant. Our data demonstrated an increase in the 3-year overall survival and event-free survival in nonchemorefractory recipients receiving CD45RA-depleted grafts (78.9% and 77.7%, respectively) compared to historic T-cell depleted haploHCT cohorts (46.7% and 42.7%, respectively, p=0.004, Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

The role of early natural killer cell adoptive infusion before engraftment in protecting against human herpesvirus‐6B encephalitis after naïve T‐cell‐depleted allogeneic stem cell transplantation

“…Because we did not routinely screen HHV‐6, we do not know the real incidence of HHV‐6 reactivation. We observed no toxicity related to the high rate of engraftment, with acceptable aGvHD and cGvHD rates and significant OS and EFS improvement, results similar to previous studies 2, 10–14 …”

“…Although the data are preliminary, the EFS, OS, EFS, GFRS, and cumulative incidence of relapse when NK cells were infused at day +7 were improved compared with our group's previous data on a cohort of haplo‐HSCT pediatric patients, 15,16,46 and the data are similar to those published with a larger patient cohort 2 …”

“…In this study, we performed an infusion of adoptive haploidentical NK cells on day +7, as other groups have previously reported. 2,13 Although seven (38%) patients presented HHV-6B reactivation, which is relatively high, none of them developed encephalitis. In fact, five (71.4%) of the six patients with HHV-6B reactivation received NK/ CD4 + T cells at a ratio of <2, whereas only two (20%) of the 10 patients presenting HHV-6B reactivation received a NK/CD4 + T cells at a ratio >2 (p = .013).…”

“…In addition, we previously reported preliminary in vitro data showing that NK cells were able to eliminate HHV‐6B CD4 + T cells at a ratio of 2:1 (NK/HHV6‐B CD4 + T cell). In this study, we performed an infusion of adoptive haploidentical NK cells on day +7, as other groups have previously reported 2,13 . Although seven (38%) patients presented HHV‐6B reactivation, which is relatively high, none of them developed encephalitis.…”

Optimizing the Procedure to Manufacture Clinical-Grade NK Cells for Adoptive Immunotherapy

“…CD45RA - cells can be infused into patients undergoing haploHSCT either as part of the graft, along with the mobilized CD34 + cells, or as donor lymphocyte infusions (DLI). CD45RA + depleted grafts are usually obtained from healthy donors after pharmacologic mobilization of hematopoietic stem cells using G-CSF [ 21 ], although some other protocols use non-mobilized apheresis [ 22 ]. CD45RA + depleted fractions for DLI are obtained after non-mobilized apheresis [ 23 ].…”