Outcomes of Post-Transplant Cyclophosphamide Prophylaxis in Matched Sibling Donor Allogeneic Hematopoietic Cell Transplant: A Retrospective Study at a Single Tertiary Center in Saudi Arabia
Authors: Yahia Alaa Eldein , Alsakkaf Abdullah , Alshehri Faisal Abdullah , Issa Zahra AlHaj , Alsuhaibani Aws A. , Howaidi Jude , Alrajhi Abdullah M. , Albtoosh Bilal , Mohamed Gamal , Alsughayir Ammar Hasan , Alnoamani Mohammed S , Alzahrani Kamal , Alshehry Nawal F , Tailor Imran K , Marei Mohammed , Motabi Ibraheem H , Alhumaid Muhned , Alshehri Hassan 
Published: December 2024

Introduction
Graft-versus-host disease (GVHD) is a major complication post allogeneic stem cell transplantation (allo-HSCT). Initially, post-transplant cyclophosphamide (PTCy) emerged in haploidentical transplantation to mitigate barriers including GVHD. The utilization of PTCy-based prophylaxis is being steadily embraced in allo-HSCT from HLA-matched related donors (MRDs) (Williams, et al, 2020). Different studies have shown a favorable response whereas other studies noted poor overall survival and delayed neutrophil engraftment compared with standard cyclosporine-based prophylaxis. Despite the conflicting evidence, the role of PTCy in this setting requires further investigation. We plan to evaluate the outcome of PTCy in MRD allo-HSCT recipients.
Methods
This is a single tertiary center retrospective cohort study conducted in King Fahad Medical City, Riyadh, Saudi Arabia that included data between 2018-2023. Patients who are ≥ 14 years old with acute leukemia who have undergone MRD allo-HSCT were included in our study. The patients were divided into two groups those who received PTCy-based prophylaxis and those who received non-PTCy-based prophylaxis. The study endpoints include cumulative incidence of relapse (CIR), non-relapse mortality (NRM), relapse-free survival (RFS), and overall survival (OS). RFS is defined as the time from transplant until relapse or death from any cause. OS is defined as the time from diagnosis to death or last follow-up. Patient demographics and treatment-related outcomes will be reported using descriptive statistics. OS and RFS probabilities will be calculated using the Kaplan-Meier analysis. A P-value of &lt;0.05 is considered statistically significant.
Results
42 patients were included in our study with 25 and 17 patients receiving non-PTCy-based and PTCY-based prophylaxis, respectively. In terms of primary diagnosis, 11 (64.7%) patients had AML in the PTCy group and 16 (64%) had AML in the non-PTCy group. The mean time to ANC engraftment was 20.31 (±5.50) for PTCy and 16.79 (±5.01) for the non-PTCy group (P=0.057).
11out of 17 patients (64%) who received PTCy achieved complete remission on day 100 post-transplant assessment compared to 16 out of 25 patients (64%) in non-PTCy group. Relapse occurred in 4 patients (23.5%) of those who received PTCy compared to 13 (52%) in the non-PTCy group. The incidence of acute and chronic GVHD was similar between the two groups. Hemorrhagic cystitis occurred in 31% of the patients in the PTCy group. The CIR in the PTCy group was 24% compared to 47% in the non-PTCy group (P = 0.079). The 2-year NRM was 16.5% and 7.5% with PTCy and non-PTCy-based prophylaxis, respectively (P = 0.173). The RFS rate at 2 years was 60% with PTCy and 45% in the non-PTCy group [95%CI, 34%-77.9% vs 25.8%-62% (P = 0.338)]. With PTCy, the 2-year OS rate was 66% compared to 74% with non-PTCy-based prophylaxis [95% CI, 45%-80.8% vs 48.5%-88.8%; (P = 0.558). Compared to ALL, patients with AML who received PTCy had a 2-year OS rate of 80% compared to 72% in those who did not receive PTCy, whereas, the 2-year OS rate for ALL patients who received PTCy was 53% and 29% in the non-PTCy group.
Conclusion
In our study population, the use of PTCy with conditioning regimen in patients with acute leukemias receiving HSCT from MSD was associated with significant lower CIR but was associated with a non-significant increased NRM. The RFS and OS showed non-significant difference between the PTCy and non-PTCy-based prophylaxis groups. Further studies needed to determine the role of PTCy in MSD-HSCT.