Impact of Day 11 Methotrexate Dose Adjustments due to Mucositis on the Outcomes Following Allogeneic Stem Cell Transplant in the Setting of Anti Thymocyte Globulin (ATG) Based GVHD Prophylaxis.

Abstract

Background: Dose adjustments of Day 11 Methotrexate (MTx) for GVHD prophylaxis after allogeneic hematopoietic stem cell transplantation (HCT) are common due to mucositis, renal injury, or other reasons. The impact of omitting or adjusting doses of MTx in the era of ATG-based GVHD prophylaxis remains unexplored.

Methods: We retrospectively analyzed the outcomes of all adult patients undergoing allogeneic HCT who received ATG-based GVHD prophylaxis at The Ottawa Hospital from January 2019 to December 2022. We compared outcomes of patients having only Day 11 MTx dose reductions due to mucositis(MTxRD group) with patients receiving full dose MTx on all 4 days (MTxFD group). The impact of Day 11 MTx dose reduction on outcomes were assessed using Kaplan-Meier analyses and log rank test.

Results: Three hundred and four patients (median age 58 [17-74] years; 64% male) underwent allogeneic HCT during the study period. Baseline characteristics were similar between the MTxRD group (n = 69) and MTxFD group (n = 199) except for an increased proportion of MAC regimens in MTxRD group. The incidence of severe aGVHD (7.2% vs. 7.5%; p = 0.96) and chronic GVHD (15.9% vs. 15.6%; p = 0.89) were not different between the two groups. The 2-year OS (59% vs. 69.8%; p = 0.11), GRFS (42.4% vs. 47.6%; p = 0.32), NRM (17.7% vs. 12.2%; p = 0.45) or relapse/progression (CIR 27.4 vs. 26.6%; p = 0.55) were also similar between the two groups.

Conclusions: In patients receiving ATG-based GVHD prophylaxis regimens, there were similar GVHD and survival outcomes in patients who received no or reduced D11 MTx when compared to full dose MTx. Dose adjustments of D11 MTx due to mucositis appear to be safe in the era of ATG-based GVHD prophylaxis regimens.