Recommended Citation
Williams M, Franzen E, Arshad S, et al. Toxicity and Outcomes Associated With Reduced-Dose Post-Transplant Cyclophosphamide. Presented at Scientific Day; May 21, 2025; Park Ridge, IL.
Abstract
Background/Significance:
Post-transplant cyclophosphamide (PTCy) is an effective prophylaxis (ppx) for graft-versus-host disease (GVHD) as shown in the BMT CTN 1703 trial. However, there is limited reporting of significant adverse events such as cardiotoxicity (CT) and hemorrhagic cystitis (HC). One study noted a day +100 CT incidence of 19% and > 2 times higher risk with PTCy versus not. Another identified a lower incidence of 7.4%, but non-PTCy patients had similar rates. Furthermore, they determined risk factors for CT based on pre-existing comorbidities (age, hypertension, cardiac history, diabetes) and discovered risk stratification scores 2-4 increased CT risk (HR 2.2 - 5.6).
Purpose:
The primary objective was to describe PTCy-related adverse events and outcomes when utilizing reduced PTCy doses.
Methods:
This retrospective, single-center review evaluated patients who received an allogeneic stem cell transplant from any donor type with PTCy-based GVHD ppx between December 6, 2022, and June 1, 2024. Patients were evaluated at day +100 for CT, HC, and select viral infections. Day +180 assessments reported the incidence of acute and chronic GVHD, relapse, and survival. Descriptive statistics, Kaplan-Meier methods, and cumulative incidence were calculated using R (V.2023.12.1).
Results:
Eleven patients were evaluated following exclusion of three who received full dose PTCy (100 mg/kg). Baseline characteristics included a median age of 65.3 years (40.4-76), 91% male, 81% AML/MDS, and 81% received a reduced intensity conditioning. Cardiac risk scores were 0-1 (64%), 2 (36%), and 3-4 (0%). All received PTCy 80 mg/kg total. Overall, 63.6% developed CT, nearly all of which were grade 2 pericardial effusions, and 36.4% experienced HC. Grades 1-2 acute GVHD and relapse were 45.5% (0% 3/4) and 33.3%, respectively, with an estimated day +180 overall survival of 90%. Cytomegalovirus and Epstein-Barr virus reactivation cumulative incidence was 18.2% and 0%, respectively.
Conclusion:
Despite utilizing lower dose PTCy, CT, and HC incidence was high compared to references despite no high cardiac risk scores, but efficacy remained comparable. While most CT may be trivial incidental findings during routine post-transplant surveillance, two severe events occurred in patients with low cardiac risk scores. Further studies are needed to uphold proposed CT risk stratification and determine optimal PTCy doses.
Presentation Notes
Presented at Scientific Day; May 21, 2025; Park Ridge, IL.
Full Text of Presentation
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Document Type
Oral/Podium Presentation
Toxicity and Outcomes Associated With Reduced-Dose Post-Transplant Cyclophosphamide
Background/Significance:
Post-transplant cyclophosphamide (PTCy) is an effective prophylaxis (ppx) for graft-versus-host disease (GVHD) as shown in the BMT CTN 1703 trial. However, there is limited reporting of significant adverse events such as cardiotoxicity (CT) and hemorrhagic cystitis (HC). One study noted a day +100 CT incidence of 19% and > 2 times higher risk with PTCy versus not. Another identified a lower incidence of 7.4%, but non-PTCy patients had similar rates. Furthermore, they determined risk factors for CT based on pre-existing comorbidities (age, hypertension, cardiac history, diabetes) and discovered risk stratification scores 2-4 increased CT risk (HR 2.2 - 5.6).
Purpose:
The primary objective was to describe PTCy-related adverse events and outcomes when utilizing reduced PTCy doses.
Methods:
This retrospective, single-center review evaluated patients who received an allogeneic stem cell transplant from any donor type with PTCy-based GVHD ppx between December 6, 2022, and June 1, 2024. Patients were evaluated at day +100 for CT, HC, and select viral infections. Day +180 assessments reported the incidence of acute and chronic GVHD, relapse, and survival. Descriptive statistics, Kaplan-Meier methods, and cumulative incidence were calculated using R (V.2023.12.1).
Results:
Eleven patients were evaluated following exclusion of three who received full dose PTCy (100 mg/kg). Baseline characteristics included a median age of 65.3 years (40.4-76), 91% male, 81% AML/MDS, and 81% received a reduced intensity conditioning. Cardiac risk scores were 0-1 (64%), 2 (36%), and 3-4 (0%). All received PTCy 80 mg/kg total. Overall, 63.6% developed CT, nearly all of which were grade 2 pericardial effusions, and 36.4% experienced HC. Grades 1-2 acute GVHD and relapse were 45.5% (0% 3/4) and 33.3%, respectively, with an estimated day +180 overall survival of 90%. Cytomegalovirus and Epstein-Barr virus reactivation cumulative incidence was 18.2% and 0%, respectively.
Conclusion:
Despite utilizing lower dose PTCy, CT, and HC incidence was high compared to references despite no high cardiac risk scores, but efficacy remained comparable. While most CT may be trivial incidental findings during routine post-transplant surveillance, two severe events occurred in patients with low cardiac risk scores. Further studies are needed to uphold proposed CT risk stratification and determine optimal PTCy doses.
Affiliations
Aurora St. Luke's Medical Center, Advocate Lutheran General Hospital