Background: Post-transplant cyclophosphamide (PTCy) with reduced-intensity conditioning for allogeneic hematopoietic cell transplant (allo-HCT) has become a standard approach for graft-versus-host disease (GVHD) prophylaxis, especially in older adults and those with comorbidities. Previous research has shown that PTCy is associated with reduced transplant related toxicity compared to traditional calcineurin inhibitor-based regimens like tacrolimus and methotrexate (Bolaños-Meade et al., 2023). This established 100mg/kg dosing (50mg/kg on days +3 and +4) as standard. Reduced total PTCy dosing (80 mg/kg) has shown efficacy in haploidentical transplantation, with comparable GVHD rates and survival outcomes (Sugita et al., 2021, Fuji et al, 2024), supporting its use in older patients to minimize toxicities. However, direct comparisons of 100 vs. 80 mg/kg PTCy in FluMel100-conditioned patients remain limited.

Methods: In this single-center retrospective chart review at Oregon Health & Science University, we examined disease response, toxicity, and GVHD outcomes among patients conditioned with FluMel100 who received either PTCy 100 mg/kg (PTCy100) or 80 mg/kg (PTCy80). Patients were stratified by PTCy dose, and we evaluated outcomes including: 1-year overall survival (OS), 1-year relapse-free survival (RFS), 100-day RFS, relapse incidence, transplant-related mortality, acute GVHD (aGVHD) incidence and severity (per MAGIC criteria), aGVHD onset timing and organ involvement, engraftment timing, length of initial immunosuppression, and hospital length of stay. Continuous variables were compared using the Mann-Whitney U test, categorical variables using Fisher's Exact Test, survival outcomes were analyzed with Kaplan Meier estimates compared with log-rank test.

Results: 54 patients were included (27 per group) with a minimum follow-up of 54 days. Median age was higher in the PTCy100 group (72 vs. 66 years, p<0.001). Most patients had AML (PTCy80: 17/27; PTCy100: 15/27), and nearly all received unrelated donor grafts (26/27 per group); 1 patient in each group had an HLA-matched sibling donor. All grafts were peripheral blood stem cells collected via apheresis. Engraftment occurred in 26/27 patients in both groups. Median hospital stay was similar (23 days PTCy100 vs. 22 days PTCy80).

Median follow-up was 213 days (PTCy80) and 630 days (PTCy100). Overall survival (OS) was 92.6% in PTCy80 vs. 85.2% in PTCy100, with 1-year OS of 92.6% and 88.9%, respectively (p=0.851). The 1-year relapse rate was 18.5% in both groups (5/27; p=0.247), and relapse-free survival (p=0.769) and 100-day survival (p=0.619) were not significantly different. These outcomes will be updated as more early-cohort patients reach the 1-year mark.

Acute GVHD (any grade) occurred more frequently in PTCy80 (63.0%) than PTCy100 (33.3%), with significant differences in grade distribution (p=0.0208). Grade 1 aGVHD was more common in PTCy80 (13/27 vs. 5/27), while severe aGVHD (grades 3–4) occurred in 2 patients (PTCy80) vs. 4 (PTCy100). The skin was the most commonly involved organ, with no difference in organ distribution. Median onset of aGVHD was earlier in PTCy80 (39 vs. 44 days, p=0.0346). Cause-of-death analysis showed no significant difference between relapse- and non-relapse-related mortality (p=0.333).

Summary: PTCy80 was associated with similar 1-year OS, RFS, compared to PTCy100 in patients receiving FluMel100, though relapse data are still maturing. Interestingly, the 80 mg/kg group had a higher incidence of low-grade aGVHD, earlier onset of aGVHD but comparable rates of severe aGVHD, relapse, and non-relapse mortality. Findings suggest 80mg/kg PTCy may effectively provide GVHD prophylaxis without increasing severe aGVHD or transplant-related mortality. 80mg/kg may be feasible for patients at higher risk for toxicity. However, no clear advantage to 80mg/kg dosing has been uncovered in our data analysis to date.

Moving forward, we are analyzing engraftment data, minimal residual disease, and pre-HCT disease status, time from diagnosis to transplant, GRFS (GVHD-free, RFS), and cyclophosphamide-specific toxicities to better understand any potential benefit with reduced PT-Cy dosing. We will also reassess chronic GVHD and long-term outcomes, including post-HCT maintenance.

This content is only available as a PDF.
2025
Sign in via your Institution