Kinetics of chimerism and outcomes after GvHD prophylaxis with PTCy vs MTX post-HSCT

Evaluation of donor chimerism is commonly used post-transplant to assess graft function. However, there is a lack of studies evaluating the kinetics of chimerism in patients receiving PTCy, which is widely used as standard GvHD prophylaxis.

A retrospective study to compare chimerism kinetics after PTCy and MTX for GvHD prophylaxis included 500 adult patients who underwent allo-HSCT at Mayo Clinic, Rochester, US, between January 2018 and June 2023. The primary outcomes assessed were time to relapse, NRM, and OS. Conditioning regimens were classified as MAC or RIC/NMA, per CIBMTR definitions. Full donor chimerism was defined as ≥95% donor cells; mixed chimerism as <95%. In total, 125 patients received PTCy, and 375 received MTX for GvHD prophylaxis. Results were published in Transplantation and Cellular Therapy by Baranwal et al.

Key learnings

CD33 (myeloid) chimerism reached full donor levels in nearly all patients across groups. Patients treated with PTCy had more consistent full CD3 (T-cell) chimerism than MTX, especially with MAC.

Mixed CD3 chimerism on Day +90 was associated with inferior RFS in the MAC + PTCy group. 1-year RFS was 40% (mixed) vs 89.2% (full chimerism). No such association seen in RIC + PTCy or in MTX recipients.

Overall, no significant difference in 1-year OS (76.6% vs. 80.2%; p = 0.42) or RFS (68.7% vs. 63.2%; p = 0.24) was observed between PTCy and MTX groups. 

In this study, mixed CD3 chimerism was a poor prognostic marker in patients receiving MAC + PTCy. Preemptive interventions, including reducing immunosuppression or DLI, may improve outcomes in high-risk patients with mixed CD3 chimerism.