Summary.A retrospective study was conducted in 1216 cases to investigate the possible association between tobacco smoking and the risk of haematological malignancies. A small, but not significant, increase in malignancy was observed in smokers. Significant association was demonstrated between tobacco smoking and acute nonlymphoblastic leukaemia, and myelodysplastic syndromes. The duration and amount smoked increased the risk; heavy smokers presented significant positive associations with overall malignancies, acute nonlymphoblastic leukaemia, myelodysplastic syndromes, and monoclonal gammopathy of undetermined significance, whereas light smokers did not present any significant association. These data support a causal relationship between certain haematological malignancies and tobacco smoking. Further research is needed to examine the risk according to dose-response effect, and the variation in risk according to the histological subtype of the malignancy.

A case-control study was conducted in 620 cases of hematological malignancies and in 1,240 age- and sex-matched controls in order to verify the possible association between occupation, toxic substances exposure, and the risk of hematological neoplasias. The results demonstrate that farmers and industrial workers have a significant risk for hematological malignancies. Exposure to asbestos, aromatic hydrocarbons, fertilizers, mineral oils, pesticides, and radiations is associated with a significant increase in the risk for these malignant diseases. These data are in agreement with previously reported data, and require a confirmation in larger, prospective studies.

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a serum monoclonal component (M-component), but no evidence of multiple myeloma, macroglobulinaemia, amyloidosis or other plasma cell proliferative disease. A long-term follow-up study (median 11.5 years) has been carried out in 263 cases of MGUS, 159 males (60.5%) and 104 females (39.5%), aged 40-89 years (median 66.5 years). The actuarial probability for malignant transformation was 6.1, 15.4 and 31.3% at 5, 10 and 20 years, respectively. At the final evaluation, 157 patients (59.7%), 119 (45.3%) of whom with no increase and 38 (14.4%) with an increase in serum M-component, died of causes unrelated to MGUS and without development of any plasma cell proliferative disease; 47 patients (17.9%) were still alive without increase in M-component; 11 patients (4.1 %) were still alive and at follow-up presented values of serum M-component > 30 g/l without any evidence of plasma cell proliferative or lymphoproliferative disease; 48 patients (18.3%) developed multiple myeloma (35 cases, 13.1%), solitary plasmacytoma of the bone (2 cases, 0.8%), macroglobulinaemia (4 cases, 1.6%), malignant lymphoma (3 cases, 1.2%), amyloidosis (2 cases, 0.8%), chronic lymphocytic leukaemia (1 case, 0.4%), and plasma cell leukaemia (1 case, 0.4%). The patients developing multiple myeloma, solitary plasmacytoma, macroglobulinaemia and plasma cell leukaemia had an increase in serum M-component, whereas no increase was found in malignant lymphoma, amyloidosis and chronic lymphocytic leukaemia. These findings and the data in the literature suggest that MGUS could be considered a preneoplastic condition; since no clinical and laboratory features are able to identify in advance the patients at high risk of disease progression, each patient must be followed up indefinitely.

A retrospective study was conducted in 285 cases of monoclonal gammopathy of undetermined significance (MGUS) and in 570 sex- and age-matched hospital controls in order to investigate the possible association between socioeconomic status, residence, alcohol and tobacco habits, occupation, occupational exposure to toxic substances, chronic antigenic stimulation, and risk of MGUS. Significant associations with the risk of MGUS were found for farmers (P < 0.005) and for workers in industry (P < 0.025). Occupational exposure to asbestos, fertilizers, mineral oils and petroleum, paints and related products, pesticides, and radiation was significantly (P < 0.05) associated with an increase in risk of MGUS. Chronic immune-stimulating conditions, when considered as a group, presented a significant (P < 0.025) association with the risk of MGUS, but no specific disease has been found to be significantly associated. These data are in agreement with the previous reports on multiple myeloma, suggesting that these factors may play an important role in the development of monoclonal gammopathies. However, these findings need to be confirmed in prospective larger population-based studies.

The diurnal rhythm in the circulating serum levels of erythropoietin (EPO) were determined in a group of 20 adult clinically-healthy subjects, in a group of 10 patients with myeloma without renal impairment and 10 patients with myeloma and renal failure. Venous blood samples were drawn during the span of a whole day and every 4 hr, starting from midnight, for the measurement of serum EPO levels by radioimmunoassay (RIA). Statistical analysis was carried out by means of the "cosinor" method. Results show that the controls and the myeloma patients without renal insufficiency present significant (P < 0.05) circadian rhythms in serum EPO levels; no rhythm (P < 0.05) was detected in patients with myeloma and renal failure. Patients with myeloma and renal failure have significant (P < 0.05) lower mean daily levels and diurnal fluctuations of EPO than the other groups, whereas the patients with myeloma without renal involvement present higher (P < 0.05) mean daily levels and lower (P < 0.05) diurnal variations of EPO than controls; no differences (P > 0.05) exist between the groups regarding peaks of rhythms. These data confirm the existence of a physiological circadian rhythm in serum EPO concentrations, with maximum in the afternoon, and they suggest that renal failure is an important cause of anemia and loss of EPO circadian rhythm in patients with myeloma.