Waldenström's macroglobulinaemia

Last reviewed: 1 Mar 2023
Last updated: 07 Feb 2023



History and exam

Key diagnostic factors

  • age >70 years
  • male sex
  • white ancestry
More key diagnostic factors

Other diagnostic factors

  • history of IgM monoclonal gammopathy of undetermined significance (MGUS)
  • family history of B-cell lymphoma or myeloma
  • family history of WM with or without monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma
  • fatigue
  • anorexia
  • infections
  • peripheral neuropathy
  • weight loss
  • fever
  • Raynaud's phenomenon
  • splenomegaly
  • lymphadenopathy
  • hepatomegaly
  • purpura
  • haemorrhage
Other diagnostic factors

Risk factors

  • IgM component monoclonal gammopathy of undetermined significance (MGUS)
  • family history of B-cell lymphoproliferative disease or multiple myeloma
  • family history of WM
  • hepatitis C virus (HCV)
More risk factors

Diagnostic investigations

1st investigations to order

  • FBC with differential
  • haematinic test (iron, vitamin B12, and folate)
  • renal function panel
  • LFTs
  • CRP
  • high-resolution serum protein electrophoresis (SPEP) with immunofixation
  • high-resolution urine protein electrophoresis (UPEP) and immunofixation
  • serum free light chains
  • cold agglutinins and cryoglobulins
  • lactate dehydrogenase
  • beta-2 microglobulin
  • serum albumin
  • relative serum viscosity
  • bone marrow biopsy
  • CT chest, abdomen, and pelvis
More 1st investigations to order

Investigations to consider

  • lymph node biopsy
  • 18-F-deoxyglucose (18F-FDG) PET/CT chest, abdomen, and pelvis
  • quantitative immunoglobulins
  • anti-myelin-associated glycoprotein (MAG) antibodies
  • anti-sulfatide IgM antibodies
  • electromyography
  • fat pad biopsy
  • prothrombin time (PT) and activated partial thromboplastin time (APTT)
  • viral serology (hepatitis B and C, and HIV)
  • genetic mutation testing
More investigations to consider

Treatment algorithm



symptomatic with low tumour burden

symptomatic with high tumour burden


responders to initial rituximab-containing treatment

relapse or refractory disease



Guy Pratt, MD, FRCP, FRCPath

Consultant Haematologist

University Hospitals Birmingham NHS Foundation Trust

Honorary Professor

Institute of Immunology and Immunotherapy

College of Medical and Dental Sciences

University of Birmingham




GP has received honoraria for speaking, advisory board memberships, and travel support from Janssen, Celgene, Takeda, Binding Site Ltd, and Amgen.


Dr Guy Pratt wishes to gratefully acknowledge Dr Boris Kobrinsky and Dr Kenneth Hymes, the previous contributors to this topic.


BK and KH declare that they have no competing interests.

Peer reviewers

Shaji Kumar, MD


Department of Hematology

Mayo Clinic




SK declares that he has no competing interests.

Madhav Dhodapkar, MD

Professor of Medicine

Chief, Section of Hematology

Department of Internal Medicine

Yale University School of Medicine

New Haven



MD declares that he has no competing interests.

Xavier Leleu, MD, PhD

Instructor in Hematology

Department of Hematology

Hopital Huriez CHRU




XL has received lecture fees and research funding from Janssen-Cilag, Celgene, Chugai, Amgen, Novartis, Mundipharma, and Roche. XL is an author of a number of references cited in this topic.

Shayna Sarosiek, MD

Assistant Professor

Harvard Medical SchoolBostonUSA


SS has received research and consulting funding from BeiGene and ADC Therapeutics.

  • Differentials

    • Multiple myeloma (MM)
    • Low-grade B-cell lymphomas (e.g., follicular lymphoma)
    • Chronic lymphocytic leukaemia (CLL)
    More Differentials
  • Guidelines

    • NCCN clinical practice guidelines in oncology: Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma
    • NCCN clinical practice guidelines in oncology: hematopoietic cell transplantation (HCT)
    More Guidelines
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