Serum Thymidine Kinase as a Marker of Disease Activity in Patients With Multiple Myeloma

Abstract

Serum thymidine kinase (STK) levels have recently been used to detect tumour regression and progression in a number of hematological malignancies. In this study, patients with myeloma were monitored longitudinally for STK and several other potentially useful tumour markers to determine which laboratory parameters are the most useful for differentiating between stable and progressive disease. STK was determined by radioenzyme assay, lymphocyte surface markers were analysed by flowcytometry, plasma cell labelling index (LI) by immunofluorescence with anti BU-1, serum B2-microglobulin (SB2M) by radioimmunoassay and M proteins by radial immunodiffusion. Detailed multiparameter longitudinal investigations of 5 patients and ongoing studies of 70 other patients suggest that STK is a more reliable marker of progressive disease than either SB2M, LI, M-protein or CD10 positive lymphocytes. A rise in STK during the emergence of progressive disease at least paralleled and usually preceded any change in the other parameters which often did not change at all. All samples from patients with progressive disease (n = 29) had a STK above the normal range (0-5U/l) whereas 76% of patients in clear stable disease had a STK within the normal range. All samples (n = 34) from patients with light chain isotype suppression (LCIS) had STK values of less than 12 U/L and 82% of samples (n = 33) from patients without LCIS had a STK above the normal range (0-5U/L). The correlation between STK and LI was r = 0.65; p less than 0.001 (n = 21). The radioenzyme assay for STK is simple, reproducible and a valuable tool for monitoring patients with myeloma and when used in conjunction with other clinical and laboratory investigations, aids in the separation of patients with stable myeloma from patients whose disease is progressive.

Longitudinal analysis of circulating myeloma cells detected by allele specific mRNA in situ hybridization

“…In this longitudinal study, the number of circulating myeloma cells varied from 0.1 to 23% of the mononuclear cells and confirmed other laboratory (serum M-protein and thymidine kinase) and clinical markers of the clinical state of the patient. The data from these studies also confirms our previous observation the serum thymidine kinase is an excellent monitor of the disease status throughout the course of the disease [24].…”

“…Immunoglobulin levels were determined on a Roche (Nutley, NJ) Cobas FARA, and serum thymidine kinase levels were determined by radioenzyme assay [24]. …”

The Labelling Index of Primitive Plasma Cells Determines the Clinical Behaviour of Patients with Myelomatosis

“…Extensive studies have demonstrated that a LI of 0 . The LI is an indicator of disease activity and has been shown to correlate with other markers of proliferation, such as serum thymidine kinase levels (STK) (Brown et al, 1989) and nucleoside transporter levels (Petersen et al, 1994). The combination of LI with serum b 2 -microglobulin level provides the most significant prognostic information of any of the known prognostic factors (Griepp et al, 1988).…”

Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-β1 and interleukin-10

“…Disease status was classified as either stable or progressive after clinical assessment and laboratory investigations that included determination of active lytic lesions, full blood count, serum calcium level, serum creatinine level and creatinine clearance, paraprotein level, Bence-Jones proteinuria, serum ␤2M level, and serum thymidine kinase level. 20 Patients were enrolled in the Australian Leukaemia Study Group myeloma trial. 21 Serum for enzyme-linked immunosorbent assay (ELISA) was separated and frozen until the day of assay.…”