Progression and Transformation of Clonally Heterogeneous B-cell Lymphoma.

Indolent B- cell non-Hodgkin lymphoma can transform into aggressive lymphoma. We extend our prior mathematical model to analyze and predict transformation. To provide additional confidence in our model, we compare it with SCID mouse data for combination therapy of Diffuse Large B-cell Lymphoma, an aggressive form of the disease. We develop a two cell model that includes indolent and aggressive clones but no immune response and use it to predict transformation. An approximate model for the time to transformation is derived that provides insight regarding scaling effects. We then add an immune response and therapeutic measures, and illustrate the complex interactions among the various processes, with a focus on transformation. The implications for initial diagnosis and treatment of non-Hodgkin lymphoma are discussed.