{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:59:03Z","timestamp":1784368743332,"version":"3.55.0"},"reference-count":36,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2002,3,15]]},"abstract":"<jats:p> PURPOSE: To evaluate the natural history of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), identify early predictors of evolution, and assess whether associated conditions correlate with disease progression. <\/jats:p><jats:p> PATIENTS AND METHODS: A total of 1,231 consecutive patients with either MGUS (n = 1,104) or SMM (n = 127) diagnosed from July 1975 to March 1998 were included in the study. Cumulative survival probability and cumulative probability of transformation into lymphoproliferative disease were calculated by means of the Kaplan-Meier estimator. Univariate and multivariate Cox models were used to identify possible predictors of malignant evolution. <\/jats:p><jats:p> RESULTS: Cumulative transformation probability at 10 and 15 years was 14% and 30%, respectively. At a median follow-up of 65 months (range, 12 to 239 months), 64 MGUS cases (5.8%) evolved to multiple myeloma (MM) (n = 43), extramedullary plasmacytoma (n = 1), primary amyloidosis (n = 1), Waldenstr\u00f6m\u2019s macroglobulinemia (n = 12), non-Hodgkin\u2019s lymphoma (n = 6), and B-chronic lymphocytic leukemia (n = 1). At a median follow-up of 72 months (range, 12 to 247 months), 25 SMMs (19.7%) evolved to overt MM. A lower evolution risk was observed in MGUS than in SMM (P &lt; .0001). Greater than 5% marrow plasmacytosis, detectable Bence Jones proteinuria, polyclonal serum immunoglobulin reduction, and high erythrocyte sedimentation rate (ESR) were independent factors influencing MGUS transformation. SMM progression correlated with greater than 10% marrow plasma cells, detectable Bence Jones proteinuria, and immunoglobulin (Ig) A isotype. Neither concomitant diseases nor immunosuppression correlated with progression. <\/jats:p><jats:p> CONCLUSION: Careful evaluation of marrow plasmacytosis, urinary paraprotein, background immunoglobulins, ESR, and paraprotein isotype might help identify at presentation patients with benign monoclonal gammopathies requiring stricter monitoring. <\/jats:p>","DOI":"10.1200\/jco.2002.20.6.1625","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T08:46:10Z","timestamp":1487925970000},"page":"1625-1634","source":"Crossref","is-referenced-by-count":290,"title":["Prognostic Factors for Malignant Transformation in Monoclonal Gammopathy of Undetermined Significance and Smoldering Multiple Myeloma"],"prefix":"10.1200","volume":"20","author":[{"given":"Clara","family":"Cesana","sequence":"first","affiliation":[{"name":"From the Department of Hematology, Bone Marrow Transplantation Centre, and Laboratory of Clinical Biochemistry and Hematology, Niguarda C\u00e0 Granda Hospital, Milan; Department of Biometry and Clinical Epidemiology, Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo General Hospital, Pavia; and Department of Hematology, University of Parma, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Klersy","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Bone Marrow Transplantation Centre, and Laboratory of Clinical Biochemistry and Hematology, Niguarda C\u00e0 Granda Hospital, Milan; Department of Biometry and Clinical Epidemiology, Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo General Hospital, Pavia; and Department of Hematology, University of Parma, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciana","family":"Barbarano","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Bone Marrow Transplantation Centre, and Laboratory of Clinical Biochemistry and Hematology, Niguarda C\u00e0 Granda Hospital, Milan; Department of Biometry and Clinical Epidemiology, Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo General Hospital, Pavia; and Department of Hematology, University of Parma, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Nosari","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Bone Marrow Transplantation Centre, and Laboratory of Clinical Biochemistry and Hematology, Niguarda C\u00e0 Granda Hospital, Milan; Department of Biometry and Clinical Epidemiology, Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo General Hospital, Pavia; and Department of Hematology, University of Parma, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Crugnola","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Bone Marrow Transplantation Centre, and Laboratory of Clinical Biochemistry and Hematology, Niguarda C\u00e0 Granda Hospital, Milan; Department of Biometry and Clinical Epidemiology, Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo General Hospital, Pavia; and Department of Hematology, University of Parma, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Pungolino","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Bone Marrow Transplantation Centre, and Laboratory of Clinical Biochemistry and Hematology, Niguarda C\u00e0 Granda Hospital, Milan; Department of Biometry and Clinical Epidemiology, Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo General Hospital, Pavia; and Department of Hematology, University of Parma, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livio","family":"Gargantini","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Bone Marrow Transplantation Centre, and Laboratory of Clinical Biochemistry and Hematology, Niguarda C\u00e0 Granda Hospital, Milan; Department of Biometry and Clinical Epidemiology, Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo General Hospital, Pavia; and Department of Hematology, University of Parma, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simonetta","family":"Granata","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Bone Marrow Transplantation Centre, and Laboratory of Clinical Biochemistry and Hematology, Niguarda C\u00e0 Granda Hospital, Milan; Department of Biometry and Clinical Epidemiology, Scientific Direction, Istituto di Ricovero e Cura a Carattere Scientifico San Matteo General Hospital, Pavia; and Department of Hematology, University of Parma, Parma, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Valentini","sequence":"additional","affiliation":[{"name":"From the Department of Hematology, Bone Marrow Transplantation Centre, and Laboratory of Clinical Biochemistry and Hematology, Niguarda C\u00e0 Granda Hospital, Milan; 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