Comparison of Tacrolimus/Methotrexate and Post-Transplant Cyclophosphamide Graft-Versus Host Disease Prophylaxis for Haploidentical and Matched Allogeneic Stem Cell Transplantation Demonstrates Improved Overall Survival and Reduced Mortality, Shorter Length of Stay, Less Peritransplant Toxicity with Post-Transplant Cyclophosphamide
Authors: Merin Noah , Kim Haein , Linhares Yuliya , Merchant Akil , Darrah Justin M. , Sasine Joshua , Lee Hannah , Vescio Robert Allen , Oveisi David , McGalliard Brittany , Rejali Ali , VanStrien Patricia , Klapper Ellen B. , Hakimian Behrooz , Chute John , Paquette Ronald 
Published: December 2024

Background: Posttransplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis was developed to enable the use of haploidentical donors for patients undergoing allogeneic stem cell transplantation (alloHSCT), then used for matched-donor transplants. In 2016, we transitioned from utilizing calcineurin inhibitor/methotrexate-based GVHD prophylaxis to PTCy, for all patients undergoing alloHSCT (using haploidentical, matched-related, and matched-unrelated donors).
Objective: Statistically evaluate the change in alloHSCT outcomes that occurred after adoption of universal PTCy, to assess the effect of the GVHD prophylaxis strategy, as well as other programmatic changes (graft source, conditioning regimens, donor selection).
Study Design: This is a single-center retrospective cohort study of adult patients who underwent alloHSCT at Cedars Sinai Medical Center between January 2010 and September 2021. We compared outcomes in the pre-PTCy era (2010 - 2016) to outcomes in the era of PTCy (2016 - 2021). 432 patients were included; 180 received PTCy-based GVHD prophylaxis, and 252 patients received non-PTCy GVHD prophylaxis. Kaplan-Meier estimates and Cox regression models were built to compare outcomes based on the type of GVHD prophylaxis received (Tac/MTX pre-2016 versus PTCy-tacrolimus-mycophenolate post-2016).
Results: Hospital stay was 29 ± 15.9 days (Median ± Std) in the pre-PTCy era, and 26 ±9.9 days in the PTCy era (p &lt; 0.001). Post-transplant hospital stay was 23 ± 13 in the pre-PTC and 19 ± 8.5 days with PTCy (p &lt; 0.001). The number of patients requiring opioids after transplant was greater in the pre-PTCy era compared to the post-PTCy era (94.12 % vs 81.01%, p &lt;0.0001).
Overall Survival increased in the PTCy era compared to the pre-PTCy era (at 1 year, 87% versus 62%; p &lt;0.0001), and the difference in OS persisted at 2 years and 3 years. Relapse-free survival was higher in the PTCy era (HR: 0.55, 95% CI (0.42-0.71); p&lt;0.0001). There was no difference in the cumulative incidence of relapse at 1 year between the two groups (17% PTCy versus 26% pre-PTCy, p=0.0661). Non-Relapse Mortality at 1 year was lower in the PTCy group (10% PTCy versus 22% non-PTCy; p=0.0020).
Acute GVHD was lower in the PTCy group: grade II-IV at day 100 was 20% in PTCy, versus 33% in the non-PTCy group (p=0.0016); grade III-IV at day 100 was 5% versus 15% (p=0.0008). The 1-year cumulative incidence of cGVHD with peripheral-blood stem cell transplants was similar between the two groups, 39% in the PTCy era and 42% in the PTCy group (p=0.3321), but there was a difference in the rate of extensive cGVHD favoring use of PTCy (23% with PTCy versus 33% without, which approached significance; p = 0.053).
Patients in the PTCy era achieved higher one-year GVHD and relapse-free survival (GRFS) compared to patients in the pre-PTCy era (37%: PTCy versus 19%: non-PTCy, p &lt;0.0001). In the multivariate Cox regression model, PTCy was associated with better OS [HR: 0.40, 95% CI (0.46-0.96); p=0.0001], better RFS [HR: 0.66, 95% CI (0.46-0.96); p=0.0300], and lower NRM [HR: 0.33, 95% CI (0.16-0.69); p=0.0034]. No difference in Relapse between the two groups was shown [HR:1.12, 95% CI (0.73-1.72); p=0.6053].
Conclusion: Patients who underwent alloHSCT utilizing PTCy displayed significantly improved overall survival at 1 year compared to patients treated with predominantly methotrexate and calcineurin inhibitors, significantly improved relapse-free survival (RFS), lower rate of NRM, lower rates of acute GVHD, with no difference in rates of cGVHD. Hospital stay was 6 days shorter and fewer patients required opiates (less mucositis with PTCy). These data support the utilization of PTCy for GVHD prophylaxis for all HLA donor match grades and graft sources.