Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases
Ramón García-Sanz
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorSilvia Montoto
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAgustín Torrequebrada
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAlfonso García De Coca
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJosé Petit
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAnna Sureda
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJosé Antonio Rodríguez-García
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorPilar Massó
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAna Pérez-Aliaga
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorMaría Dolores Monteagudo
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorIsabel Navarro
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorGemma Moreno
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorCarmen Toledo
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAránzazu Alonso
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorCarles Besses
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJoan Besalduch
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorIsidro Jarque
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorPerla Salama
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJosé Angel Hernández Rivas
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorBlanca Navarro
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJoan Bladé
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJesús F. San Miguel
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorRamón García-Sanz
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorSilvia Montoto
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAgustín Torrequebrada
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAlfonso García De Coca
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJosé Petit
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAnna Sureda
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJosé Antonio Rodríguez-García
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorPilar Massó
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAna Pérez-Aliaga
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorMaría Dolores Monteagudo
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorIsabel Navarro
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorGemma Moreno
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorCarmen Toledo
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAránzazu Alonso
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorCarles Besses
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJoan Besalduch
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorIsidro Jarque
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorPerla Salama
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJosé Angel Hernández Rivas
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorBlanca Navarro
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJoan Bladé
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorJesús F. San Miguel
Spanish Group for the Study of Waldenström Macroglobulinaemia and PETHEMA (Programme for the Study and Treatment of Haematological Malignancies)
Search for more papers by this authorAbstract
In this report we analyse the presenting features of a series of patients diagnosed with Waldenström macroglobulinaemia (WM) in Spain over the last 10 years. Criteria for diagnosis required a serum monoclonal IgM protein 30 g/l and > 20% bone marrow lymphocytes. Two hundred and seventeen patients were included in the study, with a median age of 69 years and male/female ratio of 2:1. The most common symptoms at diagnosis were anaemia (38%), hyperviscosity (31%), B symptoms (23%), bleeding (23%) and neurological symptoms (22%). Sixty-one patients (27%) were asymptomatic at diagnosis and, to date, 32 of them have not received chemotherapy. Variables predicting a shorter survival free of therapy were haemoglobin < 12·5 g/dl and high β2microglobulin (β2M). The 83% of patients who did receive treatment were distributed as follows: chlorambucil/prednisone (43%), intermittent chlorambucil (11%), continuous chlorambucil (26%), cyclophosphamide/vincristine/prednisone (COP, 13·5%) and other (6·5%). Response to therapy was complete in 2%, partial in 48% and minor in 10%. Finally, 28% and 13% of patients presented stable and progressive disease, respectively, which was more common among patients treated with COP. Progression-free survival was 43% at 5 years, with three independent predictors for shorter progression-free survival (PFS): COP treatment, age > 65 and B symptoms at diagnosis. The 10-year projected overall survival (OS) was 55%. The two most frequent causes of death were development of second malignancies (31%), or infections (19%). The two main variables predicting a poor OS were hyperviscosity and high β2M. In summary, this study favours the use of chlorambucil-based therapy as the standard treatment for WM, and describes a subset of patients who should be considered as suffering a smouldering form and who therefore do not require treatment for a long period of time.
References
-
Andriko, J.-A.,
Aguilera, N.S.I.,
Chu, W.S.,
Nandedkar, M.A.,
Cotelingam, J.D. (1997) Waldenström's macroglobulinemia. A clinicopathologic study of 22 cases.
Cancer, 80, 1926–1935.DOI: 10.1002/(sici)1097-0142(19971115)80:10<1926::aid-cncr9>3.3.co;2-f
10.1002/(SICI)1097-0142(19971115)80:10<1926::AID-CNCR9>3.0.CO;2-L CAS PubMed Web of Science® Google Scholar
- Bladé, J., San Miguel, J.F., Alcalá, A., Maldonado, J., Sanz, M.A., García-Conde, J., Moro, M.J., Alonso, C., Besalduch, J., Zubizarreta, A., Besses, C., González Brito, G., Hernández-Martín, J., Fernández-Calvo, J., Rubio, D., Ortega, F., Jiménez, R., Colominas, P., Faura, M.V., Font, L., Tortosa, J., Domingo, A., Fontanillas, M., Rozman, C., Estapé, C. (1993) Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients. Journal of Clinical Oncology, 11, 1165–1171.
- Brouet, J.C. & Fermand, J.P. (1986) Macroglobulinémie de Waldenström. Hemopathies Malignes (ed. by R. Zittoun), pp. 539–553. Flammarion, Paris.
- Case, D.R., Ervin, T.J., Boyd, M.A., Redfield, D.L. (1991) Waldenström macroglobulinemia: long term results with the M2 protocol. Cancer Investigation, 9, 1–7.
- Dhodapkar, M.V., Jacobson, J.L., Gertz, M.A., Rivkin, S.E., Roodman, G.D., Tuscano, J.M., Shurafa, M., Kyle, R.A., Crowley, J.J., Barlogie, B. (2001) Prognostic factors and response to fludarabine therapy in patients with Waldenstrom macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003). Blood, 98, 41–48.
- Dimopoulos, M.A. & Alexanian, R. (1994) Waldenström macroglobulinemia. Blood, 83, 1452–1459.
- Dimopoulos, M.A., Kantarjian, H., Estey, E., O'Brien, S., Delasalle, K., Keating, M.J., Freireich, E.J., Alexanian, R. (1993) Treatment of Waldenström macroglobulinemia with 2-chlorodeoxyadenosine. Annals of Internal Medicine, 118, 195–198.
- Dimopoulos, M.A., Kantarjian, H., Weber, D., O'Brien, S., Estey, E., Delasalle, K., Rose, E., Cabanillas, F., Keating, M., Alexanian, R. (1994) Primary therapy of Waldenström macroglobulinemia with 2-chlorodeoxyadenosine. Journal of Clinical Oncology, 12, 2694–2698.
- Dimopoulos, M.A., Panayiotidis, P., Moulopoulos, L.A., Sfikakis, P., Dalakas, M. (2000) Waldenstrom's macroglobulinemia: clinical features, complications, and management. Journal of Clinical Oncology, 18, 214–226.
- Facon, T., Brouillard, M., Duhamel, A., Morel, P., Simon, M., Jouet, J.P., Bauters, F., Fenaux, P. (1993) Prognostic factors in Waldenström macroglobulinemia: a report of 167 cases. Journal of Clinical Oncology, 11, 1553–1558.
- García, R., Hernandez, J.M., Caballero, M.D., Gonzalez, M., San Miguel, J.F. (1993) Immunoblastic lymphoma and associated non-lymphoid malignancies following two cases of Waldenström's macroglobulinemia. A review of the literature. European Journal of Haematology, 50, 299–301.
- Gobbi, P.G., Bettini, R., Montecucco, C., Cavanna, L., Morandi, S., Pieresca, C., Merlini, G., Bertoloni, D., Grignani, G., Pozzetti, U. (1994) Study of prognosis in Waldenström's macroglobulinemia. a proposal for a simple binary classification with clinical and investigational utility. Blood, 83, 2939–2945.
-
Groves, F.D.,
Travis, L.B.,
Devesa, S.S.,
Ries, L.A.G.,
Fraumeni, J.F. (1998) Waldenström's macroglobulinemia. Incidence patterns in the United States, 1988–94.
Cancer, 82, 1078–1081.DOI: 10.1002/(sici)1097-0142(19980315)82:6<1078::aid-cncr10>3.3.co;2-h
10.1002/(SICI)1097-0142(19980315)82:6<1078::AID-CNCR10>3.0.CO;2-3 CAS PubMed Web of Science® Google Scholar
- Herrinton, L.J. & Weiss, N.S. (1993) Incidence of Waldenström's macroglobulinemia. Blood, 10, 3148–3150.
- Kaplan, E. & Meier, P. (1958) Nonparametric estimation from incomplete observations. Journal of the American Statistics Association, 53, 457–464.
- Kyle, R.A. & Garton, J.P. (1987) The spectrum of IgM monoclonal gammopathy in 430 cases. Mayo Clinic Proceedings, 62, 719–731.
- Kyle, R.A., Greipp, P.R., Gertz, M.A., Witzig, T.E., Lust, J.A., Lacy, M.Q., Therneau, T.M. (2000) Waldenström's macroglobulinaemia. a prospective study comparing daily with intermittent oral chlorambucil. British Journal of Haematology, 108, 737–742.
- Kyle, R.A. (1991) Plasma cell proliferative disorders. In: Hematology Basic Principles and Practice (ed. by R. Hoffman, E.J. Benz, S.J. Shattil, B. Farie & H.J. Cohen), pp. 1021–1029. Churchill Livingstone, New York.
- Morel, P., Monconduit, M., Jacomy, D., Lenain, P., Grosbois, B., Bateli, C., Facon, T., Dervite, I., Bauters, F., Najman, A., Gramont, A., Wattel, E. (2000) Prognostic factors in Waldenström macroglobulinemia. a report on 232 patients with the description of a new scoring system and its validation on 253 other patients. Blood, 96, 852–858.
- Norusis, M.J. (1990) SPSS® Base System User's Guide SPSS® 40 for the Macintosh. SPSS Inc, Chicago, IL.
-
Reeves, G.K.,
Cox, D.R.,
Darby, S.C.,
Whitley, E. (1998) Some aspects of measurement error in explanatory variables for continuous and binary regression models.
Statistics in Medicine, 17, 2157–2177.
10.1002/(SICI)1097-0258(19981015)17:19<2157::AID-SIM916>3.0.CO;2-F CAS PubMed Web of Science® Google Scholar
- Spanish Cooperative Group on CLL (1991) Treatment of chronic lymphocytic leukaemia: a preliminary report of Spanish (PETHEMA) trials. Leukemia and Lymphoma, 5, 89–91.
- Waldenström, J. (1944) Incipient Myelomatosis or ‘essential’ hyperglobulinemia with fibrinogenopenia. A New Syndrome? Acta Medica Scandinavica, 117, 216–247.
- Waldenström, J.G. (1986) Macroglobulinemia. A review. Haematologica, 71, 437–440.
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