AM report 03/23/17 Monoclonal Gammopathies: Waldenströms

What is a monoclonal gammopathy?

-Proliferation of single clone of plasma cells (M protein)
-Remember M is for monoclonal, not for IgM
-Can be detected in serum and/or urine
-M protein consists of heavy chain complexed with kappa/lambda light chain or free kappa/lambda light chain. See our patient’s spike below!

monoclonal gammopathy

What can cause a monoclonal gammopathy?

-Although we commonly think about malignant processes, there are BENIGN etiologies including CTD, vasculitis, viral infections, or even post-transplant. See below for example from BCMJ

monoclonal.jpg

Credit: http://www.bcmj.org/articles/monoclonal-gammopathy-and-primary-care

What tests should you order next if you suspect a monoclonal gammopathy?

-Start with LFTS and look at your TOTAL PROTEIN and ALBUMIN level. If you see a high TP and a low albumin (high protein gap), you should worry that there is a monoclonal gammopathy
SPEP and UPEP and allow measurement of the concentration of the M protein but does NOT tell you the isotype. For that you need to do the next step
-Confirm with IMMUNOFIXATION and check free light chain assay (FLC)
-Serum Immunoglobulins can tell if you high or low but do not establish the clonality 

What are the diagnostic criteria for Waldenstrom’s Macroglobulinemia?

IgM (remember to flip that W to remember that Waldenstroms has an IgM spike) monoclonal gammopathy of any size
Greater than 10 % of Bone Marrow Biopsy show lymphoplasmacytic features
-Typical immunophenotype (B cell markers eg: CD20)

Clinical Manifestations

-Can be ASYMPTOMATIC! known as Smoldering Waldenstroms
-Due to IgM deposition, can see peripheral neuropathy and hyperviscosity syndrome.

Hyperviscosity Syndrome is a LIFE-THREATENING EMERGENCY that is treated with Plasma Exchange and symptoms can be non-specific (blurry vision, epistaxis, headache, vertigo but can cause stroke, coma or even CHF)
-Diagnosis of Hyperviscosity syndrome is CLINICAL but unlikely unless Serum Viscosity >4 CP (Centipoises) and IgM spike>4. Remember that Plasma Exchange does NOT treat the underlying cause!

-Due to infiltration, can see anemia, hepatosplenomegaly, and lymphadenopathy
-Bleeding manifestations, most commonly EPISTAXIS, but can be non-specific like fatigue, weakness, and weight loss

What are two associations with Waldenstrom’s to keep in mind?

-Associated with Type I Cryoglobulinemia (SMV with palpable purpura)
Cold agglutinin hemolytic anemia (AIHA with +DAT)

Treatment of Waldenstroms

-If asymptomatic, does NOT need to be treated but risk of developing symptoms
-If hyperviscosity syndrome==>Plasma Exchange
Medical therapy includes TKI (eg: Ibrutinib), alkylating agents (eg: Bendamustine), purine analogs (eg: Cladribine), steroids and HSCT if candidate.
-AVOID PRBC transfusions if possible as can worsen hyperviscosity. 

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