title: Stem cell transplantation as a dynamical system: are clinical outcomes deterministic?
abstract: Outcomes in stem cell transplantation (SCT) are modeled using probability theory. However, the clinical course following SCT appears to demonstrate many characteristics of dynamical systems, especially when outcomes are considered in the context of immune reconstitution. Dynamical systems tend to evolve over time according to mathematically determined rules. Characteristically, the future states of the system are predicated on the states preceding them, and there is sensitivity to initial conditions. In SCT, the interaction between donor T cells and the recipient may be considered as such a system in which, graft source, conditioning, and early immunosuppression profoundly influence immune reconstitution over time. This eventually determines clinical outcomes, either the emergence of tolerance or the development of graft versus host disease. In this paper, parallels between SCT and dynamical systems are explored and a conceptual framework for developing mathematical models to understand disparate transplant outcomes is proposed.
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Amir A
authors.initials: AA
authors.lastname: Toor
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Jared D
authors.initials: JD
authors.lastname: Kobulnicky
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Salman
authors.initials: S
authors.lastname: Salman
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Roberts
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Max
authors.initials: M
authors.lastname: Jameson-Lee
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Meier
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Scalora
authors.affiliation: Center for the Study of Biological Complexity, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Nihar
authors.initials: N
authors.lastname: Sheth
authors.affiliation: Center for the Study of Biological Complexity, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Koparde
authors.affiliation: Center for the Study of Biological Complexity, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Myrna
authors.initials: M
authors.lastname: Serrano
authors.affiliation: Center for the Study of Biological Complexity, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Buck
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Clark
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: John M
authors.initials: JM
authors.lastname: McCarty
authors.affiliation: Stem Cell Transplant Program, Department of Internal Medicine, Massey Cancer Center, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Harold M
authors.initials: HM
authors.lastname: Chung
authors.affiliation: Department of Microbiology and Immunology, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Masoud H
authors.initials: MH
authors.lastname: Manjili
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Roy T
authors.initials: RT
authors.lastname: Sabo
authors.affiliation: Department of Psychiatry and Statistical Genomics, Virginia Commonwealth University , Richmond, VA , USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
keywords: T cell repertoire; dynamical system; graft versus host disease; logistic function; stem cell transplantation