Introduction:

Post-transplant cyclophosphamide (PTCy) Initially emerged in haploidentical allogeneic hematopoietic stem cell transplants (allo-HSCT) for graft-versus-host disease (GVHD) prophylaxis. Randomized trials have expanded its application to matched sibling donor (MSD) and matched unrelated donor (MUD).

While the standard PTCy total dose is 100 mg/kg, recent studies suggested that a reduced dose might be similarly effective in preventing GVHD while reducing non-relapse mortality (NRM) and reducing PTCy significant toxicities, including bacterial infections, fungal infections, delayed engraftment, viral reactivations, hemorrhagic cystitis and cardiotoxicity.

Objective:

To evaluate the efficacy and safety of a reduced dose PTCy (70 mg/kg total dose) versus the standard dose (100 mg/kg total dose), both combined with Calcineurin inhibitors in allo-HSCT recipients from HLA-matched sibling donors (MSD).

Methods:

This is a single tertiary center retrospective cohort study conducted at King Fahad Medical City, Riyadh, Saudi Arabia that included data between 2018-2025. Patients who are ≥ 14 years old with acute leukemia and Myelodysplastic syndromes (MDS) who have undergone MSD allo-HSCT were included in our study. The patients were divided into two groups, those who received the standard dose (100 mg/kg) and those who received reduced-dose (70 mg/kg) PTCy-based prophylaxis which was divided in day +3 and day +4, both combined with Calcineurin inhibitors and Mycophenolate mofetil.

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 <0.05 is considered statistically significant.

Results:

A total of 22 patients were included in this study, 11 patients were in the standard-dose group and 11 patients were in the reduced-dose group. The median follow up was 19 months for standard dose group and 17 months for reduced dose group. There was no significant difference in the incidence of grade I-II acute GVHD (27% vs. 45%, p=0.659) and no document grade III-IV acute GVHD in either group. Chronic GVHD was observed in 4 patients in standard dose group while not observed in reduced dose group (36% vs. 0%, p = 0.090). The median time for Neutrophils engraftment was 21 days in standard dose patients and 19 day in reduced dose patients (p=0.849). The median time for platelets engraftment was 16 days in standard dose patients and 21 day in reduced dose patients (p=0.091).

There were no significant statistical differences observed in culture proven bacterial Infection (45% vs. 27%, p =0.42), culture proven fungal Infection (27% vs. 9%, p = 0.59), CMV reactivation (64% vs. 55%, p = 1), EBV Reactivation (18% vs. 9%, p = 1), BK-virus hemorrhagic cystitis (30% vs. 9%, p = 0.311) and cardiac toxicity (27% vs. 9%, p = 0.586) between standard dose group and reduced dose group respectively.

Relapse rates were same in both groups (27% vs. 27%, p = 1). Additionally, the slandered-dose group had a non-statistically significant higher non-relapse mortality (NRM) rate (9% vs. 0%, p = 1). The cumulative incidence of relapse (CIR) at 1 year was 31% for standard dose group and 27% for reduced dose group (p= 0.941). The relapse free survival (RFS) incidence of relapse at 1 year was 60% for standard dose group and 72% for reduced dose group (p= 0.621). The median OS was 19 months in the standard-dose group and 16 months in the reduced-dose group (p =0.470).

Conclusion:

In MSD allo-HSCT, the outcome of reduced- and standard-dose PTCy was comparable with possible clinical reduction hemorrhagic cystitis, fungal infections, bacterial infections and cardiac toxicity while maintaining a similar GVHD prevention, NRM and OS rates. A larger prospective study needed to demonstrate efficacy and safety.

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2025
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