Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 cases

Abstract

Summary. In this report we analyse the presenting features of a series of patients diagnosed with Waldenstro Èm 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 b 2 microglobulin (b2M). 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 b2M. 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.

Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines

“…Fifty percent of patients who are asymptomatic at diagnosis and who are observed will not require therapy within almost 3 years. 26 One in 10 patients who are managed with a watch-and-wait approach will not require therapy for 10 years. 26 This highlights the importance of careful determination of the need for treatment, particularly at the onset of the disease, so that only patients who require therapy are treated.…”

Clinical characteristics and factors predicting evolution of asymptomatic IgM monoclonal gammopathies and IgM-related disorders

“…The unequivocal histopathological evidence of bone marrow lymphoplasmacytic (LP) lymphoma (LP-NHL) irrespective of IgM concentration has been suggested to distinguish smouldering WM (sWM) from IgM-MGUS. [2][3][4][5][6][7][8][9]11,17,18 Whether this criterion allows the identification of two different prognostic subgroups has not been formally proved yet.…”

“…2,3,6,9 Although the majority will not develop symptoms, subsets of patients evolve to overt lymphoid malignancy with variable frequency. [2][3][4][5][12][13][14][15][16][17] Studies defining factors predicting malignant transformation in aIgM-MGs are lacking, and no criterion exists reliably distinguishing subpopulations with different evolution probability to active disease. The unequivocal histopathological evidence of bone marrow lymphoplasmacytic (LP) lymphoma (LP-NHL) irrespective of IgM concentration has been suggested to distinguish smouldering WM (sWM) from IgM-MGUS.…”

“…It includes MG of undetermined significance (MGUS) and preclinical WM. [1][2][3][4][5][6][7][8][9][10][11] In the absence of active lymphoproliferative disease, aIgM-MGs ought to be observed without treatment. 2,3,6,9 Although the majority will not develop symptoms, subsets of patients evolve to overt lymphoid malignancy with variable frequency.…”

“…[1][2][3][4][5][6][7][8][9][10][11] In the absence of active lymphoproliferative disease, aIgM-MGs ought to be observed without treatment. 2,3,6,9 Although the majority will not develop symptoms, subsets of patients evolve to overt lymphoid malignancy with variable frequency. [2][3][4][5][12][13][14][15][16][17] Studies defining factors predicting malignant transformation in aIgM-MGs are lacking, and no criterion exists reliably distinguishing subpopulations with different evolution probability to active disease.…”