Case 140: Summary

Thanks for your valuable input this week!

This case was about a patient who develops cold haemagglutinin disease secondary to
lymphoplasmacytic lymphoma.

Cold haemagglutinin disease is a type of cold auto-immune haemolytic anaemia associated with IgM antibodies. It can be primary or secondary to infection (e.g. Mycoplasma, EBV, CMV), auto-immune disease (e.g. SLE), and lymphoproliferative disorders.

Lymphoplasmacytic lymphoma (LPL, also known as Waldenström macroglobulinaemia) is a rare low
grade B-cell non-Hodgkin lymphoma which is typically associated with an IgM paraprotein and a
MYD88 mutation.

It is more common in males over 60 years old, and a familial component has been suggested.

Several complications can arise from LPL, including cold haemagglutinin disease, cryoglobulinaemia,
hyperviscosity syndrome, and peripheral neuropathy.

Diagnostic work-up includes blood tests (full blood count, renal/liver function testing, serum protein
electrophoresis, beta 2 microglobulin, LDH), imaging (CT chest/abdomen/pelvis) and bone marrow examination (immunophenotype, immunohistochemistry, molecular studies).

Prognostication can be established using the International Prognostic Scoring System for Waldenström Macroglobulinaemia (IPSSWM) which includes age, haemoglobin, platelet count, beta2-microglobulin, and serum monoclonal protein concentration.

Management for asymptomatic patients should be based on watchful waiting as there is no evidence to support treatment based on laboratory or radiological features alone. Nevertheless, patients with significant marrow infiltration, significant splenomegaly/lymphadenopathy, and high
IgM paraprotein levels are more likely to require treatment sooner and this should be taken into

For symptomatic patients, first line treatment options should be based on patients’ overall fitness
and performance status, treatment toxicities and patient wishes. First line therapy recommendations involve rituximab-based regiments, including DRC (dexamethasone, rituximab, cyclophosphamide), BR (bendamustine, rituximab), and FCR (fludarabine, cyclophosphamide,
rituximab). For patients unfit for these therapies, chlorambucil might be an appropriate option.

At relapse, watchful waiting is again an option if the patient is asymptomatic. In the event of
symptoms, second line chemotherapy with rituximab containing regiments should be considered along with stem cell transplantation.
High grade transformation should follow standard management options as for diffuse large B-cell

Patients are often hypogammaglobulinaemic and antimicrobial prophylaxis should be considered e.g. aciclovir, co-trimoxazole.


Owen RG, et al; British Committee for Standards in Haematology. Guidelines on the diagnosis and management of Waldenström macroglobulinaemia. Br J Haematol. 2014 May;165(3):316-33.

Kastritis E, et al; ESMO Guidelines Committee. Waldenström’s macroglobulinaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv41-iv50.

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