Comparison of ATLG and ATG for Immune Reconstitution After Allo-HSCT for Hematologic Malignancy

Overview

Allogeneic hematopoietic stem cell transplantation is the only curative treatment for malignant hematologic diseases. However, immune rejection is a major limitation in its application. In the "Beijing Protocol", the use of granulocyte colony-stimulating factor (G-CSF) in combination with anti-thymocyte globulin (ATG) can achieve "everyone has a donor". The use of ATG, however, can interfere with the recovery of immune function after transplantation, increasing the risk of life-threatening complications such as viral infections or graft-versus-host disease. Rabbit anti-human T-lymphocyte immunoglobulin (ATLG) is currently approved for the prevention of organ transplant rejection, which is produced differently from ATG. Previous studies have shown that transplant preconditioning with ATLG is effective in preventing graft-versus-host disease and even reduces the incidence of cytomegalovirus, etc. after transplantation. In this study, we will prospectively apply containing ATLG in a cohort of allogeneic hematopoietic stem cell transplantation for malignant hematologic diseases and dynamically observe the state of immune reconstitution of patients after transplantation. We will also compare it with a matched cohort of conventional combined ATGs during the same period to explore the impact of ATLG on immune reconstitution after transplantation.

Hematological malignancies (referred to as malignant hematological diseases) are a class of major diseases that pose a significant threat to human health. Currently, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains an effective, if not the sole, treatment option for hematological tumors. Due to the potential for immune rejection, HSCT has historically been constrained to HLA-compatible siblings or non-consanguineous donors, significantly restricting its clinical application. In consideration of the findings from preceding studies, Huang's research team employed the immunomodulatory property of G-CSF in conjunction with anti-thymocyte globulin (ATG) to undertake the non-in vitro eradication of T lymphocytes for haplotype-conjugate HSCT. A series of studies were published in 2004 and 2013 that utilized G-CSF in combination with ATG to facilitate HSCT implantation. These studies demonstrated a correlation between the degree of HLA non-conformity and the degree of graft-versus-host disease (GVHD). This suggests that G-CSF combined with ATG successfully crosses the human leukocyte antigen (HLA) barrier, and that haploidentical transplantation has gradually become the most clinically utilized type of transplantation. However, clinical studies and real-world results have demonstrated that the application of ATG has the potential to enhance the risk of post-transplant cytomegalovirus (CMV), EBV activation or even infection, and post-transplant lymphoproliferative disease (PTLD). A study published in 2023 utilized a retrospective analysis of clinical outcomes to examine patients who received two distinct sources of allogeneic T-cell-depleted (ATG) transplants. The findings indicated that patients who received ATLG during transplantation exhibited a reduced incidence of cytomegalovirus (CMV) infection. In a seminal study, Wang Shunqing and colleagues investigated the role, toxicities, and effects of ATG/ATLG on transplantation complications in non-myeloablative hematopoietic stem cell transplantation. Their findings demonstrated that the administration of ATG/ATLG during non-myeloablative hematopoietic stem cell transplantation was both safe and effective. Notably, it was observed to promote the implantation of hematopoietic stem cells, reduce the incidence of acute graft-versus-host disease (aGVHD), and decrease its severity. Huang Wenrong and colleagues investigated the effectiveness and safety of ATLG/ATLG in unrelated donor allogeneic peripheral hematopoietic stem cell transplantation. The study demonstrated that ATLG significantly reduced the incidence of cGVHD, decreased the occurrence of adverse events, and effectively controlled the occurrence of aGVHD. Lu Daopei et al. investigated the effectiveness and safety of ATG/ATLG in haploidentical hematopoietic stem cell transplantation to prevent graft-versus-host disease (GVHD). Their findings indicated that the dosage of ATG, at 7.5 mg/kg, was equivalent to the dosage of ATLG, at 20 mg/kg, in the context of haploidentical hematopoietic stem cell transplantation. Consequently, ATLG has been extensively utilized for immunosuppressive therapy in patients with hematologic disorders undergoing hematopoietic stem cell transplantation. A paucity of studies currently exists on the effect of ATLG on immune reconstruction after HSCT and on comparison with ATG treatment modalities. The objective of this study is to prospectively apply ATLG pretreatment in a cohort of allogeneic HSCT for malignant hematologic diseases. The study will dynamically observe the status of immune reconstruction in post-transplantation patients and compare it with a cohort of conventional combined ATG during the same period. The primary research question guiding this study is to explore the effect of ATLG on immune reconstitution after transplantation.