A Mathematical Model for Reconstitution of Granulopoiesis After High Dose Chemotherapy with Autologous Stem Cell Transplantation

Overview

Journal J Math Biol

Date 2003 Jul 29

PMID 12883857

Citations 17

Authors

Ivar Ostby

Leiv S Rusten

Gunnar Kvalheim

Per Grottum

Affiliations

Soon will be listed here.

Abstract

High dose chemotherapy supported with hematopoietic progenitor cells gives a characteristic neutropenic period (blood neutrophils < 0.5 x 10(9) c/l) ranging from 10 to 16 days. The question of a correlation between the CFU-GM content of the transplanted CD34+ cells and time to neutrophil recovery by patients having been given high-dose chemotherapy (HD-CT) with stem cell support was addressed by means of a mathematical model of granulopoiesis. The model utilizes a convection-reaction partial differential equation (PDE) with feedback from a cytokine compartment on proliferation, maturation, and mobilization of granulocytes from bone marrow to blood. The observed number of CFU-GM cells in the transplanted CD34+ cell autograft was used as input to the model. Using this approach, the observed gross relationship between CFU-GM content in the reinfused blood product and engraftment time could be reproduced. At the same time, the effects of assumed physiological mechanisms, especially some of the effects of G-CSF on proliferation rate, maturation rate, mobilization, and cell death, could be investigated and discussed relative to observed engraftment. The model makes it possible to explain how cytokines interfere with progenitor cell mobilization from bone marrow to blood, and it points out the implications of a regulating mechanism for the granulocyte maturation rate.

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References

Aurlien E, Holte H, Pharo A, Kvaloy S, Jakobsen E, Smeland E . Combination chemotherapy with mitoguazon, ifosfamide, MTX, etoposide (MIME) and G-CSF can efficiently mobilize PBPC in patients with Hodgkin's and non-Hodgkin's lymphoma. Bone Marrow Transplant. 1998; 21(9):873-8. DOI: 10.1038/sj.bmt.1701192. View

To L, Dyson P, Juttner C . Cell-dose effect in circulating stem-cell autografting. Lancet. 1986; 2(8503):404-5. DOI: 10.1016/s0140-6736(86)90096-6. View

Schmitz S, Franke H, Loeffler M, Wichmann H, Diehl V . Model analysis of the contrasting effects of GM-CSF and G-CSF treatment on peripheral blood neutrophils observed in three patients with childhood-onset cyclic neutropenia. Br J Haematol. 1996; 95(4):616-25. DOI: 10.1046/j.1365-2141.1996.d01-1948.x. View

Wang X, Fjerdingstad H, Benestad H . Maturation rate of mouse neutrophilic granulocytes: acceleration by retardation of proliferation, but no detectable influence from G-CSF or stromal cells. Stem Cells. 1999; 17(5):253-64. DOI: 10.1002/stem.170253. View

Schmitz S, Franke H, Wichmann H, Diehl V . The effect of continuous G-CSF application in human cyclic neutropenia: a model analysis. Br J Haematol. 1995; 90(1):41-7. DOI: 10.1111/j.1365-2141.1995.tb03378.x. View

Stute N, Santana V, Rodman J, Schell M, Ihle J, Evans W . Pharmacokinetics of subcutaneous recombinant human granulocyte colony-stimulating factor in children. Blood. 1992; 79(11):2849-54. View

Baiocchi G, Scambia G, Benedetti P, Menichella G, Testa U, Pierelli L . Autologous stem cell transplantation: sequential production of hematopoietic cytokines underlying granulocyte recovery. Cancer Res. 1993; 53(6):1297-303. View

Khwaja A, Carver J, Jones H, Paterson D, Linch D . Expression and dynamic modulation of the human granulocyte colony-stimulating factor receptor in immature and differentiated myeloid cells. Br J Haematol. 1993; 85(2):254-9. DOI: 10.1111/j.1365-2141.1993.tb03164.x. View

Bhatia M, Wang J, Kapp U, Bonnet D, Dick J . Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci U S A. 1997; 94(10):5320-5. PMC: 24676. DOI: 10.1073/pnas.94.10.5320. View

10.

Saito S, Kawano Y, Watanabe T, Okamoto Y, Abe T, Kurada Y . Serum granulocyte colony-stimulating factor kinetics in children receiving intense chemotherapy with or without stem cell support. J Hematother. 1999; 8(3):291-7. DOI: 10.1089/106161299320325. View

11.

Haas R, Gericke G, Witt B, Cayeux S, Hunstein W . Increased serum levels of granulocyte colony-stimulating factor after autologous bone marrow or blood stem cell transplantation. Exp Hematol. 1993; 21(1):109-13. View

12.

Nielsen L, Bender J, Miller W, Papoutsakis E . Population balance model of in vivo neutrophil formation following bone marrow rescue therapy. Cytotechnology. 2008; 28(1-3):157-62. PMC: 3449838. DOI: 10.1023/A:1008098118491. View

13.

Ramsfjell V, Bryder D, Bjorgvinsdottir H, Kornfalt S, Nilsson L, Borge O . Distinct requirements for optimal growth and In vitro expansion of human CD34(+)CD38(-) bone marrow long-term culture-initiating cells (LTC-IC), extended LTC-IC, and murine in vivo long-term reconstituting stem cells. Blood. 1999; 94(12):4093-102. View

14.

Kuwabara T, Kato Y, Kobayashi S, Suzuki H, Sugiyama Y . Nonlinear pharmacokinetics of a recombinant human granulocyte colony-stimulating factor derivative (nartograstim): species differences among rats, monkeys and humans. J Pharmacol Exp Ther. 1994; 271(3):1535-43. View

15.

Kojima S, Matsuyama T, Kodera Y, Nishihira H, Ueda K, Shimbo T . Measurement of endogenous plasma granulocyte colony-stimulating factor in patients with acquired aplastic anemia by a sensitive chemiluminescent immunoassay. Blood. 1996; 87(4):1303-8. View

16.

Jones R, Wagner J, Celano P, Zicha M, Sharkis S . Separation of pluripotent haematopoietic stem cells from spleen colony-forming cells. Nature. 1990; 347(6289):188-9. DOI: 10.1038/347188a0. View

17.

Morrison S, Weissman I . The long-term repopulating subset of hematopoietic stem cells is deterministic and isolatable by phenotype. Immunity. 1994; 1(8):661-73. DOI: 10.1016/1074-7613(94)90037-x. View

18.

Bogdan C, Paik J, Vodovotz Y, Nathan C . Contrasting mechanisms for suppression of macrophage cytokine release by transforming growth factor-beta and interleukin-10. J Biol Chem. 1992; 267(32):23301-8. View

19.

Dercksen M, Rodenhuis S, Dirkson M, Schaasberg W, Baars J, van der Wall E . Subsets of CD34+ cells and rapid hematopoietic recovery after peripheral-blood stem-cell transplantation. J Clin Oncol. 1995; 13(8):1922-32. DOI: 10.1200/JCO.1995.13.8.1922. View

20.

Madero L, Diaz M, Villa M, Balas A, Lillo R, Garcia-Sanchez F . Progenitor cell subsets and engraftment kinetics in children undergoing autologous peripheral blood stem cell transplantation. Br J Haematol. 1998; 101(1):104-10. DOI: 10.1046/j.1365-2141.1998.00662.x. View