Long-Term Follow-up of Outcomes with Ptcy Gvhd Prophylaxis in PBSC Transplant: Decreased Chronic Gvhd and Improved Non-Relapse Mortality.

Transplantation and Cellular Therapy(2024)

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Abstract
Post-transplant Cytoxan (PTCy) was originally established as a safe and effective GVHD prophylaxis in haploidentical transplants with BM grafts, resulting in low incidence of both acute & chronic GVHD (aGVHD, cGVHD), and its use was extended across donor types. Peripheral blood stem cell (PBSC) grafts are associated with higher rates of cGVHD with traditional CNI/MTX based GVHD ppx. Recent BMT-CTN 1703 study showed improved 1-year GVHD-free, RFS with PTCy compared to MTX/tacro based ppx in RIC PBSCT. Little is known about cGVHD outcomes with PTCy in PBSCT, particularly with MAC. At Fox Chase we adopted routine use of PTCy for all donor/graft types since 2014. Here we compare our institutional outcomes of PBSCT with PTCy vs non-PTCy based ppx.To evaluate survival and GVHD in PBSCT with PTCy vs non-PTCy based GVHD ppx.We retrospectively reviewed pts who received PBSCT at our program between 2007-2021. We analyzed acute/chronic GVHD and survival outcomes using Fisher exact test, logistical regression, Kaplan-Meier curves and competing risks regressions analysis. For the long-term analysis of cGVHD, pts who died within 1 year without signs of cGVHD were excluded.We identified 323 pts who received PBSCT between 2007-2021, 211 with PTCy and 112 without.Baseline pts’ characteristics are shown in Table 1. Higher proportion of pts in the PTCy group had mismatched donors.1-year non-relapse mortality (NRM), defined as mortality in CR, was significantly lower in the PTCy group (7.1 vs 14.3%, p 0.47, Fig. 1). Rate of grade 3/4 aGVHD, as well as severe and moderate cGVHD, were also significantly lower with PTCy ppx (Gr3/4 aGVHD, 9.1% vs 33.7%, P<0.001; severe cGVHD, 10.3% vs 24%, p 0.025), even though there was higher proportion of mismatched donors in the PTCy group (Fig. 2). Statistical significance was confirmed on multivariate analysis accounting for age, HCT-CI, conditioning intensity and donor/ recipient sex match.Cumulative incidence of relapse was similar between the groups, with a trend towards longer OS with PTCy (p 0.11) (Fig. 3).Our long-term follow up analysis demonstrates that in addition to significant decrease in high grade aGVHD and non-relapse (treatment related) mortality across MAC and RIC transplants, PTCy GVHD ppx results in significant decrease in moderate to severe cGVHD. Thus in the era of PTCy GVHD prophylaxis, PBSC graft is no longer a risk factor for cGHVD.
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