Definition

Waldenstrom macroglobulinemia (WM) is a distinct B-cell disorder resulting from the accumulation, predominantly in the bone marrow, of clonally related lymphoplasmacytic cells, which secrete a monoclonal IgM protein. The paramters predicting prognosis of WM are list below:

Table 1 International Prognostic Scoring System for WM.

Factor associated with WM prognosis Value
Age, yr >65
Hemoglobin, g/dL ≤11.5
Platelet count, No./mcL ≤100,000
β2-Microglobulin, mg/L >3
Monoclonal IgM, g/dL >7

Risk stratum and survival

Risk category Score Median survival, mon
Low 0 or 1 (except age) 142.5
Intermediate 2 or age >65 yr 98.6
High >2 43.5

What can WM result in?

  1. Hyperviscosity syndrome. The symptoms of hyperviscosity are due primarily to shear forces that rupture unsupported venous channels. The presentation generally includes epistaxis, gingival bleeding, and visual changes due to retinal hemorrhages.
  2. Peripheral neuropathy. Autoantibody activity to myelin-associated glycoprotein, ganglioside M1, sulfatide moieties on peripheral nerve sheaths can result in peripheral neuropathy.
  3. Hemolytic anemia. Cold or warm antibodies in WM patients can result in autoimmune hemolytic anemia.
  4. Immune complex vasculitis.

Management of WM

The identification of the asymptomatic patient is important because this group of patients do not need therapy. What this group need is closely observation. For patients with symptoms of WM, therapy should be initiated. Frontline treatment options for WM include oral alkylators, nucleoside analogs, rituximab, or the combinations of these three. Other durgs to be considered includes bortezomib and thalidomide. The goal is to reduce the paraprotein level.

Urgent treatment

WM patients with urgent situation such as symptomatic hyperviscosity, cryoglobulinemia, or moderate to severe cytopenias should be given immediate disease control. The target ot therapy is to achieve rapid paraprotein reduction. For these conditions plasmapheresis can be initially performed. But plasmapheresis is a temporizing measure until systemic chemotherapy successfully lowers the tumor mass and thereby reduces the IgM protein concentration in the serum.

Chemotherapy regimens

Chemotherapy regimen ORR VGPR CR
BDR 96% 22% Can be used for immediate disease control
RCD 78% 7% Can be used for immediate disease control
CPR 70-80% 10% Can be used for immediate disease control
FR 96% 10%  For pts. whose age> 70, but also for younger pts
VR
TR 70%
R 20-30%

Special notices

Rituximab treatment might result in a transient risk in the level of IgM, which can produce hyperviscosity requiring urgent plasma exchange. This phenomenon is called rituximab-related “flare”.

The use of nucleoside analogs in particular should be approached cautiously in patients with WM because the increased risk of disease transformation, which could lead to myelodysplasia, acute myelogenous leukemia etc.

For patients who are eligible to autologous transplantation therapy, exposure to continuous alkylator therapy or nucleoside analogs should be limited because these drugs kill stem cell too.

Response assessment

References

  1. Morie A. Gertz. Waldenstrom Macroglobulinemia: 2011 Update On Diagnosis, Risk Stratification, and Management. Am. J. Hematology. 2011 May;  86(5):411–416.
  2. Steven P. Treon. How I Treat Waldenstrom Macroglobulinemia. Blood. 2009 Sep 17; 114(12): 2375-2385.