Waldenström macroglobulinemia, also known as lymphoplasmacytic lymphoma, is a type of cancer characterised by a monoclonal proliferation of B lymphocytes that infiltrate the bone marrow and lymphoid organs with the ability to synthesise and segregate large quantities of monoclonal immunoglobulin M (IgM).

Immunoglobulins (Ig), or antibodies, are substances that circulate in the blood to defend the body by attacking any foreign substances that enter the organism. Each Ig has two heavy chains: gamma (IgG), alfa (IgA), mu (IgM), delta (IgD), or epsilon (IgE), and two light chains (kappa or delta).

Various diseases are characterised by the clonal proliferation of plasma cells. This means that they produce a single type of light chain and/or heavy chain (monoclonal component). These diseases are called monoclonal gammopathies. That is why Waldenström macroglobulinemia is classically catalogued as a monoclonal gammopathy, but from the clinical point of view it bears a greater resemblance to an indolent B-cell non-Hodgkin lymphoma (lymphoplasmacytic lymphoma).

Waldenström macroglobulinemia is a very infrequent type of neoplasia. Its incidence in Spain is 3 new cases per million, per year. It mainly affects men (70% of patients) of advanced age, the average age being 71.

Waldenström macroglobulinemia tends to have a chronic course with a very slow evolution and may remain asymptomatic for years, in which case it does not require treatment.

The main clinical manifestations are: fatigue, loss of appetite, weight loss and, occasionally, profuse sweating. The presence of large quantities of IgM may lead to hyperviscosity syndrome, which is when these proteins make the blood more viscous, interfering with its normal flow (thick blood), something that can then lead to: neurological alterations (migraine, vertigo, confusion, somnolence), vision disorder, and heart problems (heart failure). Bleeding diathesis may also be present (a redisposition to bleed anomalously) on account of the hyperviscosity and thrombopenia, which can lead to infiltration of the bone marrow. Lymphadenitis (enlarged lymph glands) may also be observed, as well as splenomegaly (enlarged spleen) and hepatomegaly (enlarged liver).

Diagnosis for Waldenström macroglobulinemia is based on bone aspiration and biopsy to demonstrate lymphomatous infiltration and the presence of the monoclonal IgM component in the proteinogram. The study also requires a complete hemogram blood test, biochemical analysis (blood sugar level, electrolyte test, renal profile and liver profile), a coagulation study, a molecular, cytogenetic and immunophenotypic analysis of the blood and bone marrow (bone marrow aspiration), a study of the fundus oculi to evaluate the hyperviscosity, and a CT scan if lymphadenitis or large tumour mass is suspected. A lymph node biopsy may also be required if there are diagnostic doubts and inflamed lymph nodes are accessible.

Incipient or asymptomatic forms of Waldenström macroglobulinemia (25% of cases) may not require treatment, it being sufficient to regularly monitor its evolution to confirm that the disease is remaining stable, or whether, on the contrary, it is progressing.

Treatment is indicated when there is: recurent fever; night sweats; weight loss; hyperviscosity syndrome data; swollen lymph nodes; or organomegaly, severe anemia or thrombopenia, coagulation alterations, kidney failure.

In cases in which treatment is required, this is generally based on the combination of two or three of the following agents: Rituximab (a monoclonal antibody that acts against the CD20 receptor specifically presented by neoplastic lymphoid cells), alkylating agents (chlorambucil, bendamustine, cyclophosphamide) and purine analogues (fludarabine and 2CdA).

75% of patients have an excellent response to these treatments that can last from 6 months to 8 years.

The only treatment for Waldenström macroglobulinemia that presents the possibility for a cure is a hematopoietic transplant. Unfortunately, the advanced age of most patients and the high toxicity of the procedure mean that this is performed on very few occasions.

In cases with symptoms of hyperviscosity, plasmapheresis is indicated until the symptoms disappear. This procedure involves completely removing the blood from the body, separating the red and white blood cells from the plasma, and then returning the blood cells to the patient substituting the thick plasma with normal plasma.

The prognosis for patients with Waldenström macroglobulinemia depends on a number of factors amongst which are the patient's age, the speed of the disease's progression, and response to treatment. For some patients the disease may be stable, or progress slowly, and they may live for many years. Other patients may have a rapidly progressing form of Waldenström macroglobulinemia. 60% of patients live for longer than 10 years after diagnosis. Around 10-15% of patients have a disease that transforms into an aggressive non-Hodgkin lymphoma, which must be treated as such.

For more quality information about Waldenström macroglobulinemia you can consult the following websites:

• Plasma cell neoplasms treatment. National Cancer Institute
• Waldenström macroglobulinemia. JANSSEN guide.
• International Waldestrom's Macroglobulemia Foundation
• About la Waldenström macroglobulinemia. Leukaemia and Lymphoma Society