RISK OF MALIGNANT TRANSFORMATION IN PATIENTS WITH MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE

The acturial probability of malignant transformation was analyzed in a series of 263 patients with monoclonal gammopathy of undetermined sig nificance (MGUS) over a 15-year period and followed from 5 to 20 years . At a median follow-up of 11.5 years, 157 patients (59.7%) had died o f causes unrelated to MGUS, 47 (17.9%) were still alive and presented no increase in monoclonal component, 11 (4.1%) presented an increase i n monoclonal component without evidence of malignant immunoproliferati ve disease, and 48 (18.3%) had developed a malignant transformation of MGUS. In particular, MGUS evolved into 35 cases of multiple myeloma, two of solitary plasmacytoma of the bone, four of macroglobulinemia, t hree of malignant lymphoma, two of amyloidosis, one of chronic lymphoc ytic leukemia, and one of plasma cell leukemia. The cumulative inciden ce of malignant transformation was 18.3%; and the actuarial risk of ma lignant transformation was 6.1, 15.4, and 31.3% at 5, IO and 20 years, respectively. The multivariate regression analysis according to Cox's proportional hazard model selected among 22 different variables estab lished at initial diagnosis of MGUS only age as the factor significant ly (P < 0.011) and negatively (b = -1.104) related to the risk of deve loping a malignant immunoproliferative disease. Therefore, patients wi th MGUS present an increased risk of developing a malignant lymphoprol iferative or plasma cell proliferative disease, and MGUS could be cons idered a pre-neoplastic condition. Since no clinical or laboratory fea tures are able to identify in advance the patients at high risk of dis ease progression, each patient must be followed up periodically and ov er an undefinite period.