Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation

Abstract

Data on whether the T cell dose of allogeneic peripheral blood stem cell (PBSC) products influences transplantation outcomes are conflicting. Using the Center for International Blood and Marrow Transplant Research database, we identified 2736 adult patients who underwent first allogeneic PBSC transplantation for acute leukemia or myelodysplastic syndrome between 2008 and 2014 using an HLA-matched sibling donor (MSD) or an 8/8-matched unrelated donor (MUD). We excluded ex vivo and in vivo T cell-depleted transplantations. Correlative analysis was performed between CD3 + T cell dose and the risk of graft-versus-host-disease (GVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS). Using maximum likelihood estimation, we identified CD3 + T cell dose cutoff that separated the risk of acute GVHD (aGVHD) grade II-IV in both the MSD and MUD groups. A CD3 + T cell dose cutoff of 14 £ 10 7 cells/kg identified MSD/low CD3 + (n = 223) and MSD/high CD3 + (n = 1214), and a dose of 15 £ 10 7 cells/kg identified MUD/low CD3 + (n = 197) and MUD/high CD3 + (n = 1102). On univariate analysis, the MSD/high CD3 + group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MSD/low CD3 + group (33% versus 25%; P = .009). There were no differences between the 2 groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. The MUD/high CD3 + group had a higher cumulative incidence of day +100 aGVHD grade II-IV compared with the MUD/low CD3 + group (49% versus 41%; P = .04). There were no differences between the 2 groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of the MSD and MUD groups failed to show an association between CD3 + T cell dose and the risk of either aGVHD grade II-IV (P = .10 and .07, respectively) or cGVHD (P = .80 and .30, respectively). Subanalysis of CD4 + T cells, CD8 + T cells, and CD4+/CD8+ ratio failed to identify cutoff values predictive of transplantation outcomes; however, using the log-rank test, the sample size was suboptimal for identifying a difference at this cutoff cell dose. In this registry study, the CD3 + T cell dose of PBSC products did not influence the risk of aGVHD or cGVHD or other transplantation outcomes when using an MSD or an 8/8-matched MUD. Subset analyses of CD4 + and CD8 + T cell doses were not possible given our small sample size.

A Prospective Study of an HLA-Haploidentical Peripheral Blood Stem Cell Transplantation Regimen Based on Modification of the Dose of Posttransplant Cyclophosphamide for Poor Prognosis or Refractory Hematological Malignancies

“…Our results regarding the effects according to the number of infused CD34 + and CD3 + cells were not consistent with some previous reports 25 – 28 . The contradictory results might, in part, be associated with a heterogeneous group of patients with different disease statuses and transplantation characteristics.…”

Use of the NIH consensus criteria in cellular and soluble biomarker research in chronic graft-versus-host disease: A systematic review

“…The study from Saad et al. that included 2,736 participants, did not specify the absolute number of patients with and without cGvHD ( 15 ). The remaining 2,090 subjects had diseases other than cGvHD (e.g., aGvHD).…”

“…*Saad et al. ( 15 ) did not specify how many control subjects they had and Hirayama et al. ( 16 ) did an analysis of a subgroup of patients from their previous study.…”

“…They included a total of 15,089 subjects, among whom 5,828 patients had cGvHD and 4,435 were controls (416 healthy individuals, 4,019 were post-transplant patients without cGvHD, out of which 3,023 were time-matched for the time since alloHCT). The study from Saad et al that included 2,736 participants, did not specify the absolute number of patients with and without cGvHD (15). The remaining 2,090 subjects had diseases other than cGvHD (e.g., aGvHD).…”

Recipe for a Graft: T Cell Dose Remains Elusive

“…In this issue of BBMT, Saad et al [1] set out to determine whether one can extract from the Center for International Blood & Marrow Transplant Research database evidence that T cell graft composition can impact graft-versus-host disease (GVHD) outcomes of patients with acute leukemia or myelodysplastic syndrome undergoing peripheral blood stem cell (PBSC) allogeneic transplantation using HLA-matched sibling donors or 8/8-matched unrelated donors. A large number of patients (n = 2376) were analyzed, allowing for predictive statistical analysis.…”