Comparison of Rabbit ATLG and ATG in Allogeneic Hematopoietic Stem Cell Transplantation for Children with Acquired Severe Aplastic Anemia

Background: Rabbit anti-human T lymphocyte globulin (ATLG) and anti-thymocyte globulin (ATG) are commonly used for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of these two ATG preparations in adult hematological malignancies and severe aplastic anemia (SAA) with allo-HSCT has been reported in previous studies. However, the efficacy of rabbit ATLG versus ATG has not yet been compared in children with SAA undergoing allo-HSCT. Accordingly, this study compared the clinical outcomes of pediatric SAA patients who received allo-HSCT with different ATG preparations.

Methods: We retrospectively reviewed patients who underwent allo-HSCT with ATLG or ATG for GVHD prophylaxis from January 2019 to March 2024. Overall survival (OS) was calculated and compared by Kaplan-Meier analysis and log-rank tests. The incidences of neutrophil engraftment, platelet engraftment, aGVHD, cGVHD, hemorrhagic cystitis (HC), Epstein-Barr virus (EBV) viremia, and cytomegalovirus (CMV) viremia in the two groups were evaluated by the Gray's test. The primary objective of this study was to compare the effect of two different ATGs on allo-HSCT outcomes of pediatric SAA patients.

Results: A total of 124 children undergoing allo-HSCT were enrolled, including 69 SAA and 55 VSAA. Thirty-five received ATLG for GVHD prophylaxis and 89 received ATG. The median age at HSCT was 8.2 years (range, 2-16 years). Seventy-two underwent haploidentical donor transplants (Haplo-HSCT), 28 underwent human leukocyte antigen (HLA)-matched unrelated donor transplants (MUD-HSCT), 20 underwent HLA-matched related transplants (MRD-HSCT), and 4 underwent umbilical cord blood transplants (UCBT). There were no significant differences observed in the baseline characteristics between two groups (include sex, age, conditioning regimen, donor type, graft source, the number of mononuclear cells (MNC) and CD34+ cell, HLA matched, donor-patient sex matched, ABO matched, all P＞0.05). We found that different ATG preparations did not influence neutrophil and platelet engraftment (11days (10-16 days) vs 11 days (10-40 days), P=0.792, and 12 days (8-16 days) vs 11 days (6-63 days), P=0.624, respectively). During a median follow-up of 33 months, there were no significant differences found between ATLG and ATG groups in terms of the 3-year OS (95.2% vs 92.9%, P=0.617), cGVHD (48.4% vs 39.6%, P=0.223), HC (38.6% vs 33.2%, P=0.421), 100-day incidences of grade I-IV aGVHD (52.6% vs 44.5%, P=0.416) and grade II-IV aGVHD (24.2% vs 17.6%, P=0.236). However, the 180-day incidences of EBV viremia and CMV viremia were significantly lower in ATLG group than in ATG group (30.5% vs 54.6%, P=0.0069 and 40.6% vs 78.2%, P=0.0022, respectively).

Conclusions: This is the first study to compare the efficacy of two different ATGs on allo-HSCT outcomes of pediatric SAA patients. In children with SAA undergoing allo-HSCT, ATLG demonstrated similar effects on GVHD and OS compared with ATG, while showing superior safety with reduced risks of EBV and CMV infection after transplantation. Prospective randomized studies are warranted to further evaluate these findings.