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Biol Blood Marrow Transplant. 2018 Nov;24(11):2216-2223. doi: 10.1016/j.bbmt.2018.07.002. Epub 2018 Jul 10.

Effect of Antihuman T Lymphocyte Globulin on Immune Recovery after Myeloablative Allogeneic Stem Cell Transplantation with Matched Unrelated Donors: Analysis of Immune Reconstitution in a Double-Blind Randomized Controlled Trial.

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Dana-Farber Cancer Institute, Department of Hematologic Malignancies, Boston, Massachusetts USA.
Dana-Farber Cancer Institute, Department of Biostatistics and Computation Biology, Boston, Massachusetts USA.
Massachussetts General Hospital Department of Hematology/Oncology, Boston, Massachussetts, USA.
Milton Hershey Medical Center, Department of Hematology/Oncology, Hershey, Pennsylvania, USA.
University of Chicago, Comprehensive Cancer Center, Chicago, Illinois, USA. University of Utah, Pediatric Hematology/Oncology.
Primary Children's Hospital, Salt Lake City, UT, USA.
Stanford Hospitals and Clinics, CA, USA.
University of Kansas Medical Center, Department of Hematology/Oncology, Kansas City, Missouri, USA.
University of North Carolina, Chapel Hill, Division of Hematology/Oncology, North Carolina, USA.
Vanderbilt University Medical Center, Department of Hematology/Oncology, Nashville, TN, USA.
Texas Transplant Unit, San Antonio, Texas, USA.
Fresenius Biotech, Lexington, MA, USA.
BMT and Leukemia Program, Washington University School of Medicine, St. Louis, Missouri, USA.


We recently conducted a randomized double-blind study in which we demonstrated that moderate/severe chronic graft-versus-host disease (cGVHD) but not cGVHD-free survival was reduced in patients receiving anti-T lymphocyte globulin (ATLG) 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. The randomized study (n = 254) included patients (aged 18 to 65 years) who underwent myeloablative transplants for acute myeloid leukemia, myelodysplastic syndrome, or acute lymphoblastic leukemia from HLA-matched unrelated donors. Ninety-one patients consented for the companion IR study (ATLG = 44, placebo = 47). Blood samples were collected on days 30, 100, 180, and 360 after hematopoietic cell transplantation (HCT), and multiparameter flow cytometry was performed in a blinded fashion. Reconstitution of CD3+ and CD4+ T cells was delayed up to 6 months post-HCT in the ATLG arm, whereas absolute regulatory T cell (Treg) (CD4+25+127-) numbers were lower only in the first 100 days. Analysis of the CD4+ Treg and conventional T cells (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 natural killer cell recovery were similar in each arm. Higher absolute counts of CD3+, CD4+, CD8+ T, Tregs, and Tconv were associated with improved overall survival, progression-free survival, and nonrelapse mortality but not moderate/severe cGVHD. Although 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.


ATLG; Immune reconstitution; Naive regulatory T cells


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