Conditioning intensity and peritransplant flow cytometric MRD dynamics in adult AML
Gabrielle Paras1, Linde M Morsink2,3, Megan Othus4
1Department of Medicine, Residency Program, University of Washington, Seattle, WA.
Abstract:
In acute myeloid leukemia (AML), measurable residual disease (MRD) before or after allogeneic hematopoietic cell transplantation (HCT) is an established independent indicator of poor outcome. To address how peri-HCT MRD dynamics could refine risk assessment across different conditioning intensities, we analyzed 810 adults transplanted in first or second remission after myeloablative conditioning (MAC; n = 515) or non-MAC (n = 295) who underwent multiparameter flow cytometry-based MRD testing before as well as 20 to 40 days after allografting. Patients without pre- and post-HCT MRD (MRDneg/MRDneg) had the lowest risks of relapse and highest relapse-free survival (RFS) and overall survival (OS). Relative to those patients, outcomes for MRDpos/MRDpos and MRDneg/MRDpos patients were poor regardless of conditioning intensity. Outcomes for MRDpos/MRDneg patients were intermediate. Among 161 patients with MRD before HCT, MRD was cleared more commonly with a MAC (85 of 104; 81.7%) than non-MAC (33 of 57; 57.9%) regimen (P = .002). Although non-MAC regimens were less likely to clear MRD, if they did, the impact on outcome was greater. Thus, there was a significant interaction between conditioning intensity and "MRD conversion" for relapse (P = .020), RFS (P = .002), and OS (P = .001). Similar findings were obtained in the subset of 590 patients receiving HLA-matched allografts. C-statistic values were higher (indicating higher predictive accuracy) for peri-HCT MRD dynamics compared with the isolated use of pre-HCT MRD status or post-HCT MRD status for prediction of relapse, RFS, and OS. Across conditioning intensities, peri-HCT MRD dynamics improve risk assessment over isolated pre- or post-HCT MRD assessments in patients with AML.
Insights
Measurable residual disease (MRD) dynamics around hematopoietic cell transplantation (HCT) in acute myeloid leukemia (AML) refine risk assessment. Tracking MRD before and after HCT improves prediction of relapse and survival outcomes.
Area of Science:
- Hematology
- Oncology
- Transplantation Medicine
Background:
- Measurable residual disease (MRD) post-allogeneic hematopoietic cell transplantation (HCT) is a key predictor of poor outcomes in acute myeloid leukemia (AML).
- Risk stratification in AML patients undergoing HCT needs refinement, particularly concerning the impact of conditioning intensity on MRD dynamics.
Purpose of the Study:
- To evaluate how peri-transplant MRD dynamics, considering both pre- and post-HCT status, refine risk assessment in AML patients undergoing HCT.
- To investigate the interplay between conditioning intensity (myeloablative vs. non-myeloablative) and MRD conversion on transplant outcomes.
Main Methods:
- Analysis of 810 adult AML patients who underwent HCT in first or second remission.
- Multiparameter flow cytometry-based MRD testing performed before and 20-40 days after HCT.
- Comparison of outcomes based on MRD status (MRDneg/MRDneg, MRDpos/MRDpos, MRDneg/MRDpos, MRDpos/MRDneg) and conditioning intensity.
Main Results:
- Patients with no MRD before or after HCT (MRDneg/MRDneg) had the best outcomes.
- MRDpos/MRDpos and MRDneg/MRDpos patients showed poor outcomes irrespective of conditioning.
- Myeloablative conditioning (MAC) achieved higher MRD clearance rates than non-MAC regimens.
- A significant interaction was observed between conditioning intensity and MRD conversion for relapse, relapse-free survival (RFS), and overall survival (OS).
- Peri-HCT MRD dynamics demonstrated higher predictive accuracy for relapse, RFS, and OS compared to isolated pre- or post-HCT MRD assessments.
Conclusions:
- Peri-transplant MRD dynamics provide superior risk stratification for AML patients undergoing HCT compared to isolated pre- or post-HCT MRD assessments.
- Understanding MRD conversion patterns in relation to conditioning intensity is crucial for optimizing transplant strategies and improving patient outcomes in AML.
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