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Impact of Post-Transplant Cyclophosphamide on the Prognostic Value of HCT-CI
Ansh Mehta1, Haesook T Kim2, Arcita Pramudita1
1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Insights
The Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) predicts outcomes in allogeneic HCT. Specific HCT-CI factors, particularly cardiac issues, impact non-relapse mortality (NRM) in patients receiving post-transplant cyclophosphamide (PTCY) prophylaxis.
Area of Science:
- Hematology
- Transplantation Immunology
- Oncology
Background:
- The Hematopoietic Cell Transplant Comorbidity Index (HCT-CI) is a standard prognostic tool for allogeneic hematopoietic cell transplantation (HCT).
- The specific impact of individual HCT-CI components on prognosis, especially with newer prophylactic strategies like post-transplant cyclophosphamide (PTCY), is not fully understood.
- Understanding these factors is crucial for refining risk stratification and improving patient outcomes.
Purpose of the Study:
- To evaluate the prognostic significance of the HCT-CI and its individual components in patients undergoing HCT for myelodysplastic syndrome or acute myeloid leukemia.
- To determine if the HCT-CI requires modification for patients receiving PTCY-based graft-versus-host disease (GVHD) prophylaxis.
- To identify specific comorbidities that influence non-relapse mortality (NRM) in the context of PTCY.
Main Methods:
- Retrospective analysis of 586 patients undergoing HCT for myelodysplastic syndrome or acute myeloid leukemia between 2018 and 2022.
- Multivariable regression analysis was employed to identify an optimized subset of HCT-CI comorbidities.
- Model fit was assessed using the Akaike information index (AIC), and predictive ability was evaluated using the C-index.
Main Results:
- A higher HCT-CI score was significantly associated with increased cumulative incidence of NRM in both univariable and multivariable analyses.
- Specific comorbidities including diabetes, infection, peptic ulcer disease, renal, rheumatologic, and severe pulmonary conditions showed a similar impact on NRM as the total HCT-CI score.
- Diabetes and cardiac comorbidities demonstrated a strong association with NRM, with cardiac comorbidity addition improving predictive accuracy specifically in the PTCY subgroup.
Conclusions:
- The HCT-CI retains its prognostic significance in the era of PTCY-based GVHD prophylaxis.
- Refinement of the HCT-CI may be necessary to optimize its predictive power in the PTCY setting.
- Further research is warranted to elucidate the relationship between cardiac comorbidities and NRM when PTCY is used for GVHD prophylaxis.
Abstract:
The hematopoietic cell transplant comorbidity index (HCT-CI) is a validated prognostic tool for baseline assessment in allogeneic hematopoietic cell transplantation (HCT). The impact of the individual components of the HCT-CI on prognosis remains unknown for patients undergoing post-transplant cyclophosphamide (PTCY) based graft versus host disease (GVHD) prophylaxis. Data were collected and validated from patients undergoing HCT for myelodysplastic syndrome or acute myeloid leukemia at our center between 2018 and 2022. Multivariable regression analysis was used to identify an optimized subset of HCT-CI; Akaike information index (AIC) was used to assess model fit; C-index was used to evaluate the predictive ability of models. From 586, 184 (31%) received PTCY; HCT-CI comorbidities were balanced between non-PTCY and PTCY- subgroups except for renal, which was only present in 8 patients. Higher HCT-CI was associated with an increased cumulative incidence of NRM in univariable (3-year NRM: 22% [≥5] versus 12% [2 to 4] versus 4.8% [0 to 1], P = .0002) and multivariable analysis (subdistribution HR 4.28 for HCT-CI ≥5, P = .0003, 2.61 for 2 to 4, P = .013). Subset of HCT-CI comorbidities-diabetes, infection, peptic ulcer disease, renal, rheumatologic, and severe pulmonary comorbidities- had a similar impact on NRM as the total score. Diabetes and cardiac comorbidities had a strong association with NRM, and the addition of cardiac comorbidities improved the C-index only in the PTCY subgroup. The HCT-CI retains prognostic significance in the PTCY era, although refinement may be required. Future studies can identify links between cardiac comorbidities and NRM when using PTCY.
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