Professor Finn Wisløff (et.al) at Ullevål Universitetssykehus started in 1984 a comprehensive study on multiple myeloma in a particular health region in Norway ( Myelomatoseprosjektet i helseregion I). All patients with a newly discovered M-component were registered during the period 1984-1986 and the patients with multiple myeloma were followed up until 1990. The aims of this study were to find the incidence of multiple myeloma, risk factors for multiple myeloma and the figures on asymptomatic multiple myeloma.
Another goal related to this study was to carry out a long term follow up of the patients with a monoclonal gammopathy of undetermined significance (MGUS). Today, about 20 years after Wisløff (et.al) started their study, the time has come to accomplish this work.
Thus, the main goals of our study has been to elucidate:
- whether patients with MGUS have greater risk of developing multiple myeloma or another malignant lymphoproliferative disease than the normal population- how many years such a malignant progression of MGUS, if any, has taken - if any of the registered parameters (blood values etc.) when MGUS were diagnosed, could be a predictor of malignant progression.
Applications to The Directorate for Health and Social Affairs and the Data Inspectorate were sent autumn 2004 to get the necessary ethical permissions related to our study.151 patients from Wisløffs (et.al) study were identified with MGUS and 40 of these were alive. Taken account for the patients that did not give a written permission to be included in the study and patient records not obtainable, a total number of 134 patients were included in the study.
During the period from September 2004 to August 2005 a number of hospitals in the South East region of Norway were visited to obtain the necessary patient information.
Among the 134 patients with MGUS, 61 (45,5%) were men and 73 (54,5%) were women. The median age when MGUS was diagnosed was 71,5 years.
17 patients (12,7 %) had developed a malignant lymphoproliferative disease as follows:
11 (64,7 %) – Multiple Myeloma2 ( 11,7 %) – Lymphoma1 (5,8 %) - Malignant Lymphoid Disease, unspecified1 (5,8 %) – Waldenströms Macroglobulinaemia1 (5,8 %) – Plasmacytoma1 (5,8 %)- Hairy Cell Leukaemia
These figures are relatively low in comparision with other related studies carried out in other countries. It is assumed that such discrepancy is due to slightly different definitions of multiple myeloma in different countries, and that the material in our study also has included patients with very small monoclonal components.
Among the patients with a malignant progression, 12 (70,6 %) were women and 5 ( 29,3 %) were men. The median age when the malignant disease was diagnosed was 73,5 years.
Of the 17 patients who developped a malignant lymphoproliferative disease, 44% had such a progression after 5 years, 9,7% after 10 years and 100% after 18 years.The cumulative risk of developing a malignant plasma cell disease for the whole patient group (134) was 5,2% after 5 years, 9,7% after 10 years and 12% after 18 years.
The results of a Cox regression model using four continuous variables (age, concentraion of M-component, creatinine, Ca, ) established at initial diagnoses of MGUS, showed that none of these factors are significant predictors for a malign progression of MGUS.
On the basis of our data and figures on incidence of multiple myeloma and related disorders in the general population, it is demonstrated that patients with MGUS have a greater risk of developing a malignant plasma cell or lymphoproliferative disease than healthy subjects. Other related international studies have a similar conclusion.