Background: Disease relapse and graft-versus-host disease (GVHD) represent significant clinical challenges for high-risk hematological malignancies(HM) patients undergoing HLA-matched sibling donor transplantation (MDST). The inclusion of lymphocyte depleting antibodies significantly reduce the incidence of GVHD in MDST. However, the resulting T-cell depletion weakens the graft-versus-leukaemia (GVL) effect, potentially increasing the rate of disease relapse.How to balance the effect of GVHD and GVL remain unclear for high-risk HM patients receiving MDST. Here, we conducted a retrospective study to compare the efficacy of two lymphocyte depleting antibodies(r-ATG and p-ALG) as the GVHD prevention strategy.

Methods:A retrospective analysis was conducted on 48 patients with high-risk HM patients who underwent MSDT at our center from January 2019 to January 2024. Among them, 22 patients were in the p-ALG group (45mg/kg), and 26 patients were in the r-ATG group (3.5-4.5mg/kg). Data of GVHD, immune reconstitution, survival and recurrence after transplantation were analysed and compared between these two groups.

Results: Our results showed that p-ALG was more likely than r-ATG to induce chronic GVHD of moderate and prolonged duration, the p-ALG group had a higher 3-year cumulative incidence of chronic GVHD than the r-ATG group (64.4±12. 6% vs. 35.7±10.7%, p=0.063). However, there was no significant difference in total acute GVHD (aGVHD) (40.9±10.5% vs. 25.3±9%, p=0.209) and 3-year extensive cGVHD (25.5±11.4% vs. 9.3±6.4%, p=0.188) between the two groups. In terms of patient prognosis, the p-ALG group showed a higher 3-year overall survival rate compared to the r-ATG group (100% vs. 75.5%±8.8%, p=0.039). Although there was no statistically significant difference in the 3-year cumulative relapse rate (CIR) between the two groups, the p-ALG group showed a longer duration of disease remission after transplantation, with a lower 3-year cumulative incidence of post-MRD+ compared to the r-ATG group (4.5%±4.4% vs. 40.5%±11%, p=0.022).High-risk cytogenetic alterations were a significant factor associated with relapse, as 66.7% of patients who experienced a relapse had these high-risk alterations. Further stratified analysis showed that the risk of relapse was significantly increased in the high-risk genetic subgroup compared with the standard-risk group (OR=15.21, 95% CI [1.14-164.057], p=0.025). However, compared with r-ATG, the use of p-ALG has a protective effect in these high-risk patients (OR=0.33, 95% CI [0.002-0.563], p=0.019).

Conclusions: In comparison to r-ATG, the administration of p-ALG in high-risk HM patients receiving MDST is associated with an increased incidence of GVHD but results in a more favorable survival prognosis. We also found the potential superior benefits of p-ALG in MSDT particularly for HM patients with high-risk cytogenetic characteristics.

Disclosures

No relevant conflicts of interest to declare.

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2024
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