Outcomes of split-dose lymphocyte-adjusted rabbit ATG in allogeneic stem cell transplant recipients.

Abstract

e18560 Background: Despite advances in graft versus host disease (GVHD) prevention, rabbit antithymocyte globulin (rATG) remains a guideline-based option (EBMT 2024), however dosing strategies are variable. Prior studies investigated absolute lymphocyte (ALC)-adjusted optimal exposure (Admiraal et al) or split-dose rATG, the latter which resulted in no grade 3/4 acute GVHD (aGVHD) while not significantly compromising relapse-free survival (Al-Kadhimi et al). We investigated an adaptation of these methodologies. Methods: This retrospective, single-center review evaluated patients who received an allogeneic stem cell transplant from any donor type with rATG/tacrolimus/methotrexate prophylaxis between 1/2020 - 12/2022. Split-dose rATG was administered the first three days of conditioning (0.5 mg/kg x 1 day then 2 mg/kg x 2 days) and day -1 (patients 1-8: 1.5 mg/kg; 9-30: 1.75 mg/kg). A 20% rATG dose increase or decrease was applied if baseline ALC >1.5 K/mcL or <0.5 K/mcL, respectively. Primarily, patients were evaluated for aGVHD by day +100. Secondary objectives included overall survival (OS), relapse, ALC recovery, and viral infections at 1 year. Kaplan-Meier methods, Cox proportional hazard, and cumulative incidence were calculated. Results: Thirty patients were evaluated with the following characteristics: median age 60 years (28.2-73.5), 63% male, 90% white, and HCT-CI ≥3 (50%). Most received myeloablative conditioning (97%) and a peripheral blood graft (97%) for AML (63%) The median baseline ALC was 0.6 K/mcL (0-1.6) and median cumulative rATG received was 6.0 mg/kg (range 5-7.5). Median follow up was 24.3 months. Overall, aGVHD incidence was 63.3% (0% G3/4). OS was 80% (2-yr estimated 70%) and cumulative incidence of relapse was 26.7%. Median ALC recovery was highest at 1 year (0.75 K/mcL) despite 91.7% of patients remaining on immunosuppression. Cytomegalovirus and Epstein-Barr virus cumulative incidence at day +365 was 33.3% and 20.3%, respectively. Cumulative ATG dose (25 mg increments) did not increase risk of anytime relapse (HR 1.15, p =0.17). Patients received a median 74% of suggested optimal ATG dosing (range: 52-106%). Conclusions: ALC-adjusted rATG did not result in severe aGVHD and relapse outcomes were comparable to referenced literature. ALC recovery remained impaired for at least one year. Further standardization of ATG-dosing, including dose individualization, is needed, ideally in a prospective setting. Primary outcome by D+100 Incidence Acute GVHD, % (95% CI)GI-II, NGIII-IV, NUnknown, N 63.3 (41.3-77.1)1603 Secondary outcomes by D+365 Overall survival, % (95% CI) a 80 (66.9-95.7) Relapse, % (95% CI) b 26.7 (9-40.9) Chronic GVHD, % (95% CI) b 64.8 (38-80) CMV, % (95% CI) b 33.3 (14.1-48.2) EBV, % (95% CI) b 20.3 (4.4-33.6) a Two-year estimated 70% (95% CI 55.4-88.5). b Censored for death prior to one year.