About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
1）Age ≧18 years, gender is not limited;
2）Histologically or cytologically confirmed diagnosis of malignant hematologic diseases;
3) First time undergoing allogeneic hematopoietic stem cell transplantation;
4) ECOG score 0-2;
Disqualifiers
1) Prior treatment with ATG, ALG, or ATLG drugs within the past six months;
2) Allergic to any component of ATLG or ATG;
3) Bacterial, viral, parasitic, or mycobacterial infections not adequately controlled by treatment, i.e., inability to undergo hematopoietic stem cell transplantation due to severe infection.
Trial design
Single group
Treatments tested in this trial
Rabbit Anti-Human T-Lymphocyte Immunoglobulin (ATLG)
DrugPatients in the ATLG arm receive ATLG instead of ATG as part of the routine conditioning regimen before allo-HSCT; ATLG is given intravenously by infusion for 4 consecutive days, after which they undergo routine transplantation.
Treatment groups
Trial outcomes
Primary outcomes
Incidence of viral infections after hematopoietic stem cell transplantation
Incidence of CMV reactivation (CMV DNA ≥10\^3) and CMV disease, incidence of EBV reactivation (incidence of EBV DNA ≥10\^5) and lymphoproliferative disorders (PTLD), incidence of hemorrhagic cystitis, incidence of herpes simplex, adenovirus, or other viruses in both groups.
Secondary outcomes
Incidence and severity of acute GVHD (aGVHD)
Acute GVHD is assessed and graded based on the modified Glucksberg criteria or the Mount Sinai Acute GVHD International Consortium (MAGIC) criteria, which evaluate the degree of involvement of the skin, gastrointestinal tract, and liver. Severity is classified as grade I (mild), II (moderate), III (severe), or IV (life-threatening). The cumulative incidence of overall aGVHD, as well as grade II-IV and grade III-IV aGVHD, will be evaluated at day 100 post-transplantation.
Incidence and Severity of Chronic Graft-Versus-Host Disease (cGVHD)
Chronic GVHD is diagnosed and graded according to the National Institutes of Health (NIH) consensus criteria, which classify cGVHD as mild, moderate, or severe based on the number of organs involved and the degree of functional impairment in each affected organ. The cumulative incidence of cGVHD will be evaluated at 6 months, 12 months, and 24 months post-transplantation
Immune Reconstitution Profiles Post-Transplantation
Immune reconstitution is assessed by measuring the absolute counts of peripheral blood lymphocyte subsets using multi-color flow cytometry. The following cell populations are quantified: CD4+ T helper cells, CD8+ cytotoxic T cells, CD19+ B cells, and CD3-CD56+ natural killer (NK) cells. Measurements are performed at four pre-specified time points post-transplant: day 30, day 60, day 90, and day 180. The absolute counts (cells/µL) and the recovery kinetics of each lymphocyte subset will be analyzed and compared between treatment groups.
Overall Survival (OS)
Overall survival is defined as the time interval from the date of hematopoietic stem cell transplantation to the date of death from any cause. Patients who are alive at the last follow-up will be censored. OS rates will be estimated using the Kaplan-Meier method and reported at 100 days, 1 year, and 2 years post-transplantation.
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