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Purging of peripheral blood stem cell transplants in AML: a predictive model based on minimal residual disease burden
Nicole Feller1, Martine C Jansen-van der Weide, Marjolein A van der Pol
1Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands.
Objective:
Minimal residual disease (MRD) present in peripheral blood stem cell (PBSC) products of AML patients may contribute to relapse. Our goal was to 1) predict leukemia recurrence based on the frequency of MRD present in PBSC products, 2) establish the efficacy of different purging procedures, and 3) integrate this into a model that enables to predict whether or not to purge.
Methods:
Minimal residual disease was measured with flow cytometry using leukemia-associated phenotypes as established at diagnosis. Toxicity of purging procedures was established using clonogenic assays. Purging procedures used were cryopreservation, hyperthermia, ether lipid ET-18-OCH3, and combinations.
Results:
Minimal residual disease in PBSC products correlated significantly with relapse-free survival (n=24, p=0.003). At a cut-off value of 0.05% MRD the relative risk of relapse was 4.6 times lower in the group with less than 0.05% MRD. As measured in 54 PBSC products, the MRD level was less than 0.05% in 17 of 54 cases, between 0.05% and 0.5% in 19 of 54 cases, and higher than 0.5% in 18 of 54 cases. Based on the MRD cut-off of 0.05%, the log tumor reduction needed to achieve this threshold is zero for the 17 of 54 cases in which MRD was below 0.05%, less than or equal to 1 log in 19 of 54 cases, and greater than 1-2 log in 18 of 54 cases. When applying purging with 25 mug/mL ET-18-OCH3 combined with cryopreservation at 10% DMSO and hyperthermia at 42 degrees C combined with cryopreservation at 10% or 4% DMSO, there was greater than or equal to 1 log depletion of AML blasts.
Conclusion:
This study establishes (1) a threshold level for MRD above which prognosis is worse, (2) that stem cell products from 69% of patients have higher than this "safe" MRD level, and (3) that ET-18-OCH3 and hyperthermia may be used to purge products in part of these patients.
Insights
Minimal residual disease (MRD) in stem cell products predicts AML relapse. Purging with ET-18-OCH3 and hyperthermia can reduce MRD levels, improving patient prognosis.
Area of Science:
- Hematology
- Oncology
- Stem Cell Transplantation
Background:
- Minimal residual disease (MRD) in peripheral blood stem cell (PBSC) products is a significant factor in acute myeloid leukemia (AML) relapse.
- Accurate quantification of MRD is crucial for predicting patient outcomes and guiding treatment decisions.
Purpose of the Study:
- To predict leukemia recurrence based on MRD frequency in PBSC products.
- To evaluate the efficacy of various purging procedures for eliminating MRD.
- To develop a model for determining the necessity of purging PBSC products.
Main Methods:
- MRD was quantified using flow cytometry and leukemia-associated phenotypes.
- The toxicity of purging methods was assessed via clonogenic assays.
- Purging techniques included cryopreservation, hyperthermia, and ether lipid ET-18-OCH3, individually and in combination.
Main Results:
- A significant correlation was observed between MRD levels in PBSC products and relapse-free survival (p=0.003).
- A threshold of 0.05% MRD was identified, below which the relative risk of relapse was 4.6 times lower.
- Purging with ET-18-OCH3 and hyperthermia achieved at least a 1-log depletion of AML blasts.
Conclusions:
- A prognostic threshold for MRD in PBSC products was established, identifying levels associated with worse outcomes.
- Approximately 69% of patients exhibited MRD levels exceeding this "safe" threshold.
- ET-18-OCH3 and hyperthermia demonstrate potential as effective purging strategies for select patient groups.
