Serum thymidine kinase in monoclonal gammopathies. A prospective study. The Cooperative Group for Study and Treatment of Multiple Myeloma.
ABSTRACT Between January 1986 and March 1990, the serum levels of thymidine kinase (TK) were evaluated at diagnosis in 97 patients with monoclonal gammopathy of undetermined significance (MGUS) and 149 patients with multiple myeloma (MM) enrolled in a prospective protocol for treatment of MM. At presentation, patients with MGUS had lower TK levels than those with Stage I MM (P less than 0.05) and the overall population of those with MM (P less than 0.0005). TK levels were increased in advanced stages in comparison with earlier ones (P less than 0.01). The TK level was related to survival. With a median follow-up of 29 months, patients with TK levels greater than 7.0 U/microliters had shorter survival times than those with lower levels (medians, 23 and 42 months; P less than 0.0001). In a multivariate analysis, TK explained most of the variability of survival (P less than 0.0001), the remaining being accounted for by serum creatinine and beta-2 microglobulin. No changes in TK levels occurred during follow-up of patients with stable MGUS, whereas TK levels increased in two patients at time of progression to overt MM. In patients with MM, TK levels decreased (P less than 0.01) in those who responded to treatment but increased in those having relapses (P less than 0.03) and those with progressive disease (P less than 0.03). These results indicate that TK has clinical and prognostic relevance in monoclonal gammopathies, and additional investigations are warranted to determine whether it is a useful tool for the clinical evaluation, staging, and follow-up of patients with MM.
- [show abstract] [hide abstract]
ABSTRACT: A recently developed deoxythymidine kinase assay utilizing 125I-iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S-TK), although in some patients values increased by more than forty-fold were found. S-TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, beta 2-micro-globulin, Ca or M-component. The distribution of S-TK values in IgG, IgA and pure Bence-Jones myeloma did not differ significantly. Patients with IgG and IgA myeloma excreting light-chain immunoglobulin in the urine had significantly higher S-TK than non-excreters. There was a significant correlation between S-TK values and tumour cell mass as determined by clinical staging. A high pretreatment S-TK (greater than 5.1 units) also distinguished a group of patients with a significantly shorter survival time. Patients with no response to initial therapy had significantly higher S-TK values than those who did respond. In longitudinal studies of 11 patients, S-TK was found to increase when the disease became more aggressive. The possibility of diagnosing disease progression at an early stage by an elevation of S-TK is discussed.British Journal of Haematology 11/1985; 61(2):215-24. · 4.94 Impact Factor
- Haematologica 73(5):365-9. · 5.94 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Seventy-five patients with previously untreated multiple myeloma were randomly treated with the association of Peptichemio, Vincristine and prednisone (PTC-VCR-P) or of melphalan and P (MPH-P) for first induction therapy. After induction, all responsive patients received MPH and P until relapse, while unresponsive patients received it until unequivocal evidence of disease progression was observed. A second induction therapy with PTC-VCR-P was then administered, except to patients resistant to this association at first induction (who received combination chemotherapy which included cyclophosphamide and adriamycin). The response rate was 58% in the PTC-VCR-P and 41% in the MPH-P group (P greater than 0.05). The PTC-VCR-P responsive patients experienced a median duration of response shorter than MPH-P responsive patients (20.3 vs 39.7, P = 0.041). Median survival from the start of treatment was 26.2 months in the PTC-VCR-P and 54.1 months in the MPH-P group of patients (P = 0.039). Stage I and II myelomas had the same response rate to PTC-VCR-P and to MPH-P, but their survival was shorter on PTC-VCR-P than on MPH-P (P = 0.014). Stage III myelomas responded more frequently to PTC-VCR-P than to MPH-P (P less than 0.02) and there was a trend to survive longer on PTC-VCR-P than on MPH-P (22.0 vs 12.5 months, P greater than 0.05).European Journal of Cancer and Clinical Oncology 08/1986; 22(7):787-91.