Recent clinical findings in chronic myeloid leukemia (CML) patients suggest that the risk of molecular recurrence after stopping tyrosine kinase inhibitor (TKI) treatment substantially depends on an individual’s leukemia-specific immune response. However, it is still not possible to prospectively identify patients that will remain in treatment-free remission (TFR). Here, we used an ordinary differential equation (ODE) model for CML, which explicitly includes an anti-leukemic immunological effect and applied it to 21 CML patients for whom BCR-ABL1/ABL1 time courses had been quantified before and after TKI cessation. Immunological control was conceptually necessary to explain TFR as observed in about half of the patients. Fitting the model simulations to data, we identified patient-specific parameters and classified patients into three different groups
according to their predicted immune system configuration ('immunological landscapes”). While one class of patients required complete CML eradication to achieve TFR, other patients were able to control residual leukemia levels after treatment cessation. Among them were a third class of patients, that maintained TFR only if an optimal balance between leukemia abundance and immunological activation was achieved before treatment cessation. Model simulations further suggested that changes in the BCR-ABL1 dynamics resulting from TKI dose reduction convey information about the patient-specific immune system and allow prediction of outcome after treatment cessation. This inference of individual immunological configurations based on treatment alterations can also be applied to other cancer types in which the endogenous immune system supports maintenance therapy, long-term disease control or even cure.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:74320 |
| Date | 01 April 2021 |
| Creators | Hähnel, Tom, Baldow, Christoph, Guilhot, Joëlle, Guilhot, François, Saussele, Susanne, Mustjoki, Satu, Jilg, Stefanie, Jost, Philipp J., Dulucq, Stephanie, Mahon, François-Xavier, Roeder, Ingo, Fassoni, Artur C., Glauche, Ingmar |
| Publisher | American Association for Cancer Research (AACR) |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1538-7445, 10.1158/0008-5472.CAN-19-2175, info:eu-repo/grantAgreement/CAPES/Post-doctoral research abroad Grant/88881.119037/2016-01/ |
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