Chronic Lymphocytic Leukemia (CLL) is the
most common peripheral blood and bone marrow cancer
in the developed world. This manuscript proposes
mathematical model equations representing the disease
dynamics of B-cell CLL. We interconnect delay differential
cell cycle models in each of the tumor-involved disease
centers using physiologically-relevant cell migration. We
further introduce 5 hypothetical case studies representing
CLL heterogeneity commonly seen in clinical practice
and demonstrate how the proposed CLL model framework
may capture disease pathophysiology across patient
types. We conclude by exploring the capacity of the
proposed temporally- and spatially-distributed model to
capture the heterogeneity of CLL disease progression. By
using Global Sensitivity Analysis, the critical parameters
influencing disease trajectory over space and time are:
(i) the initial number of CLL cells in peripheral blood,
the number of involved lymph nodes, the presence and
degree of splenomegaly; (ii) the migratory fraction of nonproliferating
as well as proliferating CLL cells from bone
marrow into blood and of proliferating CLL cells from
blood into lymph nodes; (iii) the parameters inducing nonproliferative
cells to proliferate. The proposed model offers
a practical platform which may be explored in future
personalized patient protocols once validated.