Mixed T cell CHIMERISM in bone marrow at day+30 after allogeneic stem cell transplantation: Correlation with acute GVHD grades III–IV and no impact on relapse and overall survival

Abstract

Objectives Early chimerism analysis is important to assess engraftment in allogeneic hematopoietic stem cell transplantations. Methods We retrospectively investigated the impact of T‐cell chimerism at day 30 in bone marrow on acute graft‐versus‐host disease (aGVHD), relapse, and overall survival in 142 adult allo‐transplanted patients. Results The majority of patients (89%) received myeloablative conditioning and 90% have undergone T‐cell replete donor graft. At day 30, 103 patients showed T‐complete chimerism with prevalence in haploidentical transplants, whereas 39 cases had CD3+ mixed chimerism, including 30 patients transplanted with HLA identical donors, and 21 with T‐cell donors<90%. T‐cell chimerism at day 30 was weakly inversely related to aGVHD grades II–IV (p = .078) with no cases of grades III–IV aGVHD in patients with CD3+ <95%. Mixed T‐cell chimerism did not impact on relapse (p = .448) and five of the seven patients who relapsed had T‐cell chimerism ≤90%. Older age and active disease at transplant had a statistically significant negative effect on overall survival (p = .01 and p = .0001, respectively), whereas mixed CD3+ chimerism did not. Conclusions T lymphocyte chimerism analysis at day +30 in bone marrow could identify allo‐transplanted patients at major risk of aGVHD grades III–IV (CD3+ donors >95%) mainly post‐myeloablative conditioning regimen.

After Bone Marrow Transplantation, the Cell-Intrinsic Th2 Pathway Promotes Recipient T Lymphocyte Survival and Regulates Graft-versus-Host Disease

“…For example, a recipient’s professional APCs such as dendritic cells ( 6 , 7 ) or epithelial cells ( 8 ) activate donor T lymphocytes by presenting pleomorphic transplantation Ags, present in the recipient but absent in the donor. Surviving recipient T cells can also play a role in initiation or maintenance of tissue inflammation, although recipient T cell subsets can as well regulate transplant immunity ( 9–13 ). In this context, recipient T cell–generated modulatory cytokines have been shown to dampen donor T cell activation and the subsequent cascade of events that results in GVHD ( 14 , 15 ).…”