Objective: The pathogenesis of AA (aplastic anemia) involves multiple factors, including hematopoietic stem cell dysfunction, immune dysfunction and hematopoietic microenvironment abnormalities. Notably, the abnormal activation and hyperfunction of T lymphocytes are considered primary contributors to the development of AA. Anti-thymocyte globulin (ATG) has long been used for immunosuppressive therapy of AA. Among the various types of ATG, horse-derived ATG (h-ATG) is superior to rabbit-derived ATG (rATG), which in turn outperforms anti-T-lymphocyte globulin (ATLG). In AA patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), pre-conditioning with rATG has been used for graft versus host disease (GVHD) prophylaxis. However, there are limited reports on whether ATLG pre-conditioning offers comparable efficacy to rATG. Therefore, the study was conducted to investigate whether ATLG pre-conditioning yields comparable GVHD prophylaxis efficacy to rATG pre-conditioning in pediatric AA patients undergoing transplantation.

Methods: We conducted a retrospective study on pediatric patients with hematopoietic failure who underwent allo-HSCT between December 01, 2012 and December 31, 2023. The enrollment criteria were as follows: 1. Patients underwent their first allo-HSCT; 2. Patients received rATG or ATLG for GVHD prophylaxis; 3. Patients had non-hereditary hematopoietic failure. The primary endpoint was GVHD-free and failure-free survival (GFFS). The secondary endpoints were overall survival (OS), acute GVHD (aGVHD), chronic GVHD (cGVHD) and cytomegalovirus (CMV)/Epstein-Barr virus (EBV) infection or reactivation rate. R and Free Statistic software were used for statistical analysis.

Data: A total of 406 patients were enrolled, including 221 males and 185 females. 299 were assigned to the rATG group and 107 to the ATLG group. The median age of rATG group is 6years, the same as in ATLG group. For the distribution of pre-conditioning regimens, 356 (87.7%) had received BU(2)/CY/FLU/ATG (BU), 42 (10.3%) had received TBI/CY/FLU/ATG (TBI)and 8 (2.0%) had received CY/FLU/ATG (No-BU/TBI). Specifically, 260 (87%) had received BU regimen, 33 (11%) had received TBI regimen and 6 (2.0%) had received No-BU/TBI regimen in the rATG group; 96 (89.7%) had received BU regimen, 9 (8.4%) had received TBI regimen and 2 (1.9%) had received No-BU/TBI regimen in the ATLG group. There was no difference in the distribution of pre-conditioning regimens between rATG and ATLG groups. For the distribution of transplantation types, 27 (6.7%) had undergone matched sibling donor (MSD) transplantation, 141 (34.7%) had undergone unrelated donor (URD) transplantation, 183 (45.1%) had undergone haploidentical donor (HID) transplantation and 55 (13.5%) had undergone unrelated cord blood (URCB) transplantation. Specifically, 20 (6.7%) MSD , 100 (33.4%) URD , 128 (42.8%) HID and 51 (17.1%) URCB t in the rATG group; 7 (6.5%) MSD, 41 (38.3%) URD, 55 (51.4%) HID and 4 (3.7%) URCB in the ATLG group. There was more URCB transplantation types in rATG group.

Results: At a median follow-up of 41 months (20-69.75), the 5-year OS was 82.7% (0.78-0.88) in the rATG group and 87.2% (0.81-0.94) in the ATLG group, p = 0.27. The 5-year GFFS was 75.4% (0.71-0.81) in the rATG group and 73.5% (0.65-0.83) in the ATLG group, p = 0.93. The 100-day cumulative incidence of grade II-IV aGVHD was 21.4% (16.9%-26.22%) in the rATG group and 19.62% (12.7%-27.66%) in the ATLG group, p = 0.73. The 100-day cumulative incidence of grade III-IV aGVHD was 12.71% (9.23%-16.77%) in the rATG group and 11.22% (6.11%-18.04%) in the ATLG group, p = 0.714. The 1000-day cumulative incidence of cGVHD was 6% (3%-9%) in the rATG group and 12.74% (0.7%-20.44%) in the ATLG group, p = 0.037. The 180-day cumulative incidence of CMV infection was 58.53% (52.71%-63.89%) in the rATG group and 23.36% (15.83%-31.76%) in the ATLG group, p = 0.00. The 360-day cumulative incidence of EBV infection was 14.38% (10.67%-18.62%) in the rATG group and 8.4% (4.1%-14.65%) in the ATLG group, p = 0.11.

Conclusion: In pediatric patients with acquired AA undergoing allo-HSCT, comparable GFFS, OS, 100-day grade II-IV aGVHD incidence were observed between ATLG and rATG for GVHD prophylaxis. there were higher cGVHD incidence in the ATLG group; lower incidence of CMV/EBV infection in the ATLG group.

Disclosures

No relevant conflicts of interest to declare.

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2024
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