Modeling combined chemo- and immunotherapy of high-grade non-Hodgkin lymphoma.


Moderate, but not massive intensification of CHOP-21 improves outcome in aggressive non-Hodgkin lymphoma. Adding immunotherapy with Rituximab was a break-through, but levels differences in chemotherapy. Ongoing trials attempt to optimize R-CHOP type regimens. We present a mathematical model of chemo-immunotherapy to explain published and aiming at predicting future trials comparing R-CHOP variants. We hypothesize that, for cure, the immune system must dominate residual tumor cells at the end of treatment. Chemotherapy reduces both tumor and immune cells. Rituximab immunotherapy boosts the immune response. We translate this reasoning into a differential equations model. Model parameters are estimated using data of randomized clinical trials in elderly patients. The model explains observed hazard ratios between treatments. It explains why too intense chemotherapy could be detrimental. The model is validated predicting six published independent studies. As an application, we varied treatment schedules and predict that current R-CHOP variants have only limited optimization potential.

PubMed ID: 26666299

Projects: Genetical Statistics and Systems Biology, LIFE - Leipzig Research Center for Civilization Diseases

Publication type: Not specified

Journal: Leuk Lymphoma

Human Diseases: Lymphoma

Citation: Leuk Lymphoma. 2016 Jul;57(7):1697-708. doi: 10.3109/10428194.2015.1110746. Epub 2015 Dec 15.

Date Published: 16th Dec 2015

Registered Mode: by PubMed ID

Authors: K. Rosch, M. Scholz, D. Hasenclever

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Views: 2912

Created: 9th May 2019 at 10:53

Last updated: 7th Dec 2021 at 17:58

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