The Impact of Anti-T-Lymphocyte-Globulin Dosing on Gvhd in Matched Sibling Allogeneic Stemcell Transplantation

Introduction:

Due to the graft versus tumor effect allogeneic stem cell transplantation (allo-SCT) is a curative strategy for hematological malignancies. However, its benefits are offset by non-related mortality (NRM) primarily from graft-versus-host-disease (GVHD). In vivo T-cell depletion (TCD) with Anti-T-Lymphocyte globulin (ATLG) can reduce GVHD. Although lower ATLG doses may compromise the immunosuppression effects, higher ATLG doses may offset its benefit by decreasing antiviral and graft-versus-malignancy effect by depletion of donor effector T cells. Even though the use of ATLG in allo-SCT is well established, however, data on optimal ATLG dosing in the setting of matched sibling donor (MSD) -allo-SCT is scarce.

Methods:

In this retrospective study conducted at the Department of stem cell transplantation, University Medical Center Hamburg Eppendorf (UKE) we aim to compare the transplant outcomes between recipients of 15 mg/Kg vs 30 mg/Kg ATLG as T-cell depletion in Patients undergoing allo-SCT from MRD.

Results:

In the study, 109 sequential patients (ATLG 15, n=72; ATLG 30, n=37) underwent allo-SCT between the years 2018 and 2022 from MSD for hematological conditions. PBSC was the primary stem cell source in both cohorts (ATLG-15, 99%; ATLG-30, 92%; p=0.08). In the ATLG-15 group, 13% received TBI versus none in the ATLG-30 group (p=0.025). The MAC regimen was utilized in 65% of ATLG-15 patients, compared to 27% in ATLG-30 (p<0.001). The most prevalent disease was AML in ATLG-15 (54%) and PMF in ATLG-30 (54%, p<0.001). More ATLG-15 patients were transplanted in CR (43%) than in ATLG-30 (16%, p=0.02). All ATLG-15 patients had ECOG0-1 status, against 90% in ATLG-30 (p=0.007). The median age at transplant was similar, 58 and 56 years in ATLG-15 and ATLG-30, respectively (p=0.99). All other Patients donor and transplant characteristics were comparable between the two groups.

One patient died prior to engraftment and three patients had primary graft failure in the ATLG-15 group, all remaining patients successfully engrafted. The ATLG-15 cohort showed an earlier leukocyte engraftment (median 11 days, range 9-19, p=0.001) and a tendency towards quicker platelet engraftment (median 12 days, range 8-107, p=0.06) compared to the other group's medians of 13 days (range 8-16) and 17 days (range 3-130), respectively.

Grade II-IV aGVHD at day 100 was 36% in the ATLG-15 group compared to 23% in the ATLG-30 group (p=0.45). A trend towards lower 2-year moderate/severe cGVHD was observed in the ATLG-15 group (48% vs 36%, p=0.08).

The ATLG-15 group showed a trend towards higher 2-year OS (84% vs 72%, p=0.06), however this trend disappeared on multivariate analysis (MVA) (HR 0.853 [95%CI 0.319, 2.283]; p=0.75) no other factor affected OS on MVA. The 2-year PFS was similar across both groups (ATLG-15, 63%; ATLG-30, 60%; p=0.5). On MVA only TBI had a significant effect on PFS (HR 0.310 [95%CI, 0.101, 0.957], p=0.04), none of the other factors significantly affected PFS.

There was a trend for Lower NRM in the ATLG-30 group (at 1 Yr, 0% vs 11%, p=0.09), while the two-year relapse incidences were comparable (ATLG-15, 7%; ATLG-30, 14%; p=0.2).

Conclusion:

Acknowledging the retrospective nature of our study, however our results show that a higher ATLG dose may reduce incidence of chronic GVHD in Patients undergoing allo-SCT from MSD, however our findings should be confirmed in larger prospective studies.