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Differential Clinical and Immunological Impacts of Anti–T‐Lymphocyte Globulin ( ATLG ) vs. Anti‐Thymocyte Globulin ( ATG ) in Preventing Graft‐Versus‐Host Disease Post‐Allogeneic Hematopoietic Stem Cell Transplantation: A Comparative Study
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International audience. ABSTRACT Both anti‐T‐lymphocyte globulin (ATLG‐Grafalon) and anti‐thymocyte globulin (ATG‐Thymoglobulin) prevent acute and chronic graft‐versus‐host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Despite distinct manufacturing and biological characteristics, the two brands of rabbit anti‐lymphocyte globulins have never been compared in a prospective way. In this monocentric study, 114 adult patients transplanted with a matched related or unrelated donor after receiving either ATG ( n = 50) or ATLG ( n = 64) were included to compare their clinical outcomes and broad immune reconstitution parameters. The use of ATLG, compared with ATG, was associated with a 2‐fold reduction in Grade II–IV acute GvHD incidence (Cox HR = 0.29; 95% CI 0.14–0.62, p = 0.006), similar relapse incidence, and improved severe GvHD and relapse‐free survival (GRFS) (Cox HR = 0.51; 95% CI 0.29–0.91, p = 0.027). Biologically, reduced IL‐15 but increased IL‐21 serum concentrations and a significant reduction of PD1+ T cells, mainly across all differentiated stages of CD8+ T cells, were observed in the ATLG group. Immunosequencing of vβ T cell receptor (TCR) repertoires showed similar quantitative characteristics in terms of clonality and diversity across the two groups but different qualitative features, with reduced hyper‐expanded T cell clones and higher variability in the distribution of complementarity‐determining region 3 (CDR3) lengths in the ATLG group. Altogether, these results suggest that ATLG more effectively regulates alloreactive T cell activation, leading to better prevention of acute GvHD while preserving the graft‐versus‐leukemia response. These findings led us to initiate a multicentric Phase III randomized trial comparing the two anti‐lymphocyte globulins. Trial Registration: The biological REAL GREFFE study was registered in clinicaltrial.gov under the number: NCT03357172.
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