Effect of anti-human T-lymphocyte globulin (ATLG) on immune recovery following myeloablative allogeneic stem-cell transplantation with matched unrelated donors: Analysis of immune reconstitution in a double-blind randomized controlled trial

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
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Abstract
INTRODUCTION We recently conducted a randomized double-blind study in which we demonstrated that moderate/severe cGVHD, but not cGVHD free survival, was reduced in patients receiving ATLG (Neovii) versus placebo. In a companion study, we performed immunophenotypic analysis, to determine the impact of ATLG on immune reconstitution (IR) and to correlate IR with clinical outcomes. METHODS The randomized study (n=254) included patients (18-65 years) who underwent myeloablative transplants for AML/MDS/ALL from HLA-matched unrelated donors. 91/254 patients consented for the companion IR study (ATLG=44, placebo=47). Blood samples were collected at days 30, 100, 180 and 360 post-HCT and multi-parameter flow cytometry was performed in a blinded fashion. RESULTS Reconstitution of CD3+ and CD4+ T-cells was delayed up to 6 months post- HCT in the ATLG arm, while absolute Treg (CD4+25+127-) numbers were lower only in the first 100 days. Analysis of the CD4+ Treg and Tconv (CD4+25- 127+) compartments showed a profound absence of naive Tregs and Tconv in the first 100 days post-HCT, with very slow recovery for 1 year. B-cell and NK-cell recovery were similar in each arm. Higher absolute counts of CD3+, CD4+, CD8+ T, Tregs and Tconv were associated with improved OS, PFS and NRM, but not moderate-severe cGVHD CONCLUSION While ATLG delays CD3+ and CD4+ T-cell recovery post-transplant, it has a relative Treg sparing effect after the early post-HCT period, with possible implications for protection from cGVHD. ATLG severely compromises the generation of naive CD4+ cells (Treg and Tconv), potentially affecting the diversity of the TCR repertoire and T cell responses against malignancy and infection.
Study details
Transplant Type : Matched Unrelated Donor
Treatment : GvHD Prophylaxis
Language : eng
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