TY  - GEN
TI  - Mathematical modelling of plasma cell dynamics in multiple myeloma
AV  - public
Y1  - 2017///
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/22258/
ID  - heidok22258
N2  - Plasma cell dyscrasias are characterised by accumulation of malignant plasma cells in the bone marrow. Asymptomatic multiple myeloma (AMM) evolves from monoclonal gammopathy of unknown significance (MGUS) and progresses to symptomatic myeloma involving end organ damage. Three main questions are addressed by mathematical modelling. Firstly, how is growth of malignant plasma cells characterised? Secondly, how fast does progression from early asymptomatic stages (MGUS, AMM)
to symptomatic myeloma happen? Thirdly, how many malignant plasma cells initially arrive at the bone marrow?

New mathematical models consisting of piecewise-smooth ordinary differential equations are formulated describing the dynamics of healthy and malignant plasma cells in the bone marrow and its niche. Model analysis refers to existence and uniqueness of solutions, characterisation of solutions within invariant sets, and existence and stability properties of equilibria. Partial equilibria are identified extending the classical notion of equilibria. The models are validated using clinical data consisting of serum and urine samples (n = 8398) of patients with AMM and
MGUS (n = 322 and n = 196, respectively).

Model analysis and parameter estimation imply that accumulation of malignant plasma cells can be quantified by the doubling time. A faster doubling time relates to a higher probability of progression to symptomatic myeloma and correlates with a small initial number of malignant plasma cells. Instead of one single initial malignant
plasma cell, initiation of myeloma can rather be explained by a ?malignant wave? comprised of a population of malignant plasma cells arriving at the bone marrow and perturbing healthy homoeostasis.

This thesis is the result of an interdisciplinary doctorate and the joint work with Prof. Dr. Anna Marciniak-Czochra (Institute of Applied Mathematics, Heidelberg University) as well as with PD Dr. Dr. Dirk Hose and Dr. Anja Seckinger (Multiple Myeloma Research Laboratory, Heidelberg University Hospital).
A1  - Mohr, Marcel
ER  -