Impact of Reduced-Dose of Post-Transplantation Cyclophosphamide (PTCy) in HLA-Identical and Haploidentical Hematopoietic Stem Cell Transplantation: A Retrospective Analysis
Authors: Araujo Thais Fernanda Negrão de , Rocha Luana Pompeu dos Santos , Oliveira Camila Frade de , Ferreira Camila de Fatima de Morais , Souza Breno Aires de , Puls Matheus Lopes , Santos Azevedo Fernanda , Azevedo Roberta Santos , de Moraes Pedro Henrique Arruda , de Molla Vinicius Campos , Rosa Eurides L. , Liz Caina Dabbous , Justino Caio Cesar , Fonseca Ana Marcela , Szor Roberta Shcolnik , Arrais-Rodrigues Celso 
Published: December 2024

Introduction: Post-transplantation cyclophosphamide (PTCy) has become a widely used tool as prophylaxis for graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT). Its effectiveness in controlling GVHD, particularly in haploidentical transplants with reduced-intensity conditioning (RIC), has been well-established. Recent randomized trials have expanded its application to matched sibling donor (MSD) and matched unrelated donor (MUD), even in myeloablative conditioning regimens (MAC). While the standard PTCy total dose is 100mg/kg, studies suggest that a reduced dose of 80 mg/kg might be equally effective in preventing GVHD while maintaining favorable outcomes for non-relapse mortality (NRM).
Objective: To compare the efficacy and safety of a reduced-dose (80mg/kg) PTCy with the standard dose (100mg/kg).
Methods: This retrospective analysis reviewed data from patients who underwent HSCT with PTCy prophylaxis from June 2019 to January 2024 at two transplant centers in São Paulo, Brazil.
Results: A total of 158 patients who underwent HSCT with PTCy prophylaxis were included. Median follow-up was 17 months. Acute leukemia was the underlying disease in most cases (55%). Peripheral blood was the most common stem cell source (85%) and reduced-intensity conditioning was employed in most cases (87%). Donors were haploidentical in most cases (72%), matched sibling donors (MSD) in 18%, and matched unrelated donor (MUD) in 10%. The PTCy dose of 100 mg/kg was administered to 114 patients (72%). The cohort of patients who received the reduced-dose presented a significantly higher median age as compared to the standard-dose cohort (61 vs. 40 years, p &lt; 0.001). Overall survival (OS) at 17 months was significantly higher in the reduced-dose group (82%) as compared to the standard-dose group (59%, p = 0.045). Additionally, the reduced-dose group had a lower non-relapse mortality (NRM) rate (29% vs. 11%, p = 0.037). No significant differences were observed in relapse rates (14% vs. 15%, p = non significant. - NS), acute (33% vs. 38%, p = NS), or chronic GVHD (42% vs. 39%, p = NS). Besides, there were no differences in the incidence of febrile neutropenia or CMV reactivation between the groups. After a multivariate analysis, standard-dose PTCy dose and older age remained significantly associated with higher NRM and lower OS. Patients receiving 100 mg/kg PTCy exhibited a higher risk of NRM (HR 1.12, 95% CI 1.006-1.24, p = 0.039) and lower OS (HR 1.10, 95% CI 1.02-1.20, p = 0.018). Matched-pair analysis further supported these findings with OS (HR 1.2, 95% CI 1.06-1.30, p &lt; 0.001).
Conclusion: Our findings suggest that reduced dose PTCy is feasible and seems to be associated with a lower mortality than standard-dose PTCY in allogeneic HSCT, with no detrimental effect on increase of GVHD or relapse. However, the retrospective nature of this study limits the strength of the evidence. Prospective, randomized controlled trials are needed to definitively confirm these findings.