The impact of graft composition on clinical outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic SCT

Abstract

This study examines the absolute numbers and relative proportions of CD4 þ , CD8 þ , CD14 þ and CD34 þ cells contained in allografts and their impact on early engraftment and later clinical outcomes in 141 patients with hematological malignancies who underwent unmanipulated HLA-mismatched/haploidentical hematopoietic SCT without in vitro T-cell depletion. These patients received G-CSF-primed BM grafts (G-BM) and peripheral blood grafts (G-PB) following a modified regimen of BU/CY 2 plus antithymocyte globulin. Multivariate analysis showed that high CD34 þ cell numbers were associated with accelerated plt engraftment (P ¼ 0.001). Meanwhile, patients with a higher CD4/CD8 ratio in G-BM (X1.16) had a survival disadvantage (Po0.01) and a trend towards relapse (P ¼ 0.086) after controlling for disease status. A higher CD4/CD8 was also associated with a significantly increased risk of acute GVHD grades II-IV (P ¼ 0.013), even after adjusting for an ABO major mismatch. No aspect of graft composition affected neutrophil engraftment or chronic GVHD. In conclusion, the differences in CD34 þ cell dose and the CD4/CD8 ratio in grafts seem to affect engraftment and clinical outcomes; in particular, a lower CD4/CD8 ratio in primed BM graft is associated with a survival benefit.

Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors

“…However, in our transplant settings, T-cell dose in the allograft failed to associate with the development of GVHD analyzed by Huang et al 5,32 and in this study. Several possible factors may be responsible for this.…”

Haploidentical Bone Marrow Transplantation Without T-Cell Depletion

“…21,44 Other factors, including a lower CD56 dim /CD56 bright NK cell ratio (Ͻ8.0) and a higher CD4/CD8 ratio (Ͼ1.16) in the allografts, may contribute not only to higher risk of acute GVHD but also to increased TRM and decreased OS. 21,42 Recently, Huo et al 45 reported that HLA-B mismatch was an independent risk factor for acute GVHD and TRM after HLA-haploidentical transplantation without ex vivo TCD. Researchers from Japan also showed that among patients with standard-risk diseases who received transplantation from a related donor with an HLA-1 antigen mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host direction, the presence of an HLA-B antigen mismatch was significantly associated with a lower OS rate.…”

High frequencies of CD62L+ naive regulatory T cells in allografts are associated with a low risk of acute graft-versus-host disease following unmanipulated allogeneic haematopoietic stem cell transplantation

“…No correlation between FoxP3 + Tregs and aGVHD risk was observed in our centreperformed unmanipulated allogeneic HSCT (without T cell depletion in vitro) [30,31]. Therefore, we sought to clarify whether the different reports of FoxP3 + Tregs in aGVHD were derived from different HSCT methodologies or from differences in Treg subpopulations.…”