Kinetics of tumor growth and regression in IgG multiple myeloma

Abstract

A B S T R A C T Studies of immunoglobulin synthesis, total body tumor cell number, and tumor kinetics were carried out in a series of patients with IgG multiple myeloma. The changes in tumor size associated with tumor growth or with regression were underestimated when the concentration of serum M-component was used as the sole index of tumor mass. Calculation of the total body M-component synthetic rate (corrected for concentration-dependent changes in IgG metabolism) and tumor cell number gave a more accurate and predictable estimate of changes in tumor size. Tumor growth and drug-induced tumor regression were found to follow Gompertzian kinetics, with progressive retardation of the rate of change of tumor size in both of these circumstances. This retardation effect, describable with a constant a, may be caused by a shift in the proportion of tumor cells in the proliferative cycle. Drug sensitivity of the tumor could be described quantitatively with a calculation of Bo, the tumor's initial sensitivity to a given drug regimen. Of particular clinical significance, the magnitude of a given patient's tumor regression could be predicted from the ratio of This work was presented in part at

Modelling chemotherapy resistance in palliation and failed cure

“…This variation is primarily one of model interpretation; the core difference is that Hahnfeldt et al's model considers exponential cell growth. In contrast, we consider Gompertzian tumour growth; this is a constant, exponential, retardation of the growth rate which has been found to provide a good empirical description of the decelerating growth curves exhibited by more advanced tumours (Simpson-Herren and Lloyd, 1970;Sullivan and Salmon, 1972). The Gompertz (1825) model was first applied in actuarial statistics, and subsequently in the study of growth by Winsor (1932), with Laird (1964) further illustrating that the growth for a variety of primary and transplanted tumours in the mouse, rat and rabbit satisfied the Gompertzian relation.…”

“…Gompertzian growth is critical in this paper as it provides the theoretical basis of protocol escalation (Norton, 1997) in addition to being highly relevant for advanced tumours (Simpson-Herren and Lloyd, 1970;Sullivan and Salmon, 1972). For example, reducing a protocol's rest phase entails that a Gompertzian tumour is growing at faster and faster rates at each drug application since each application yields a smaller tumour.…”

Primary Bioassay of Human Myeloma Stem Cells

“…Growth was induced with either 0.02 ml of human type 0 erythrocytes or 0.25 ml of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. 5-500 colonies appeared after [2][3] wk in culture yielding a plating efficiency of 0.001-0.1%. The number of myeloma colonies was proportional to the number of cells plated between concentrations of 105-106 and back-extrapolated through zero, suggesting that colonies were clones derived from single myeloma stem cells.…”

“…Studies of myeloma immunoglobulin (M-component) synthesis and metabolism have been applied to quantitate the total body number of myeloma cells and to follow changes in tumor mass with treatment. Such serial tumor kinetic studies, and those of the tritiated thymidine labeling index of the tumor, have provided important insights on the kinetics of growth and regression of myeloma and on approaches to treatment (1,2). However, such studies do not directly assess the key compartment of the tumor, the tumor stem cells.…”

Multiple myeloma: some recent developments

“…Growth of virtually all animal tumours can best be described by the Gompertzian curve ( The initial substantial cell kill which occurs following chemotherapy in MM is often followed by a 'plateau phase' of the disease (Sullivan & Salmon 1972). Paraprotein stabilization during the 'plateau phase' persists whether treatment is continued or not.…”