Page 1125 - Clinical Immunology_ Principles and Practice ( PDFDrive )

ChaPter 80 Monoclonal Gammopathies 1089

IgM gammopathy in the blood. The diagnosis of WM is made present with symptoms due to hyperviscosity should undergo
when the following two criteria are met: (i) presence of an IgM immediate therapeutic plasmapheresis, followed by chemotherapy
21
monoclonal paraprotein on serum immunofixation and (ii) 10% for control of the malignant clone. Median survival in WM is
or more of the bone marrow biopsy sample demonstrates infiltra- approximately 5–8 years from the time of diagnosis. However,
tion by small lymphocytes that exhibit plasmacytoid or plasma outcomes are highly variable. A staging system for WM has been
cell differentiation (lymphoplasmacytic features or lymphoplas- developed based on a prospective multicenter observational study
macytic lymphoma) with an intertrabecular pattern. This infiltrate outlined in Table 80.6. 22
+
should express a typical immunophenotype (e.g., surface IgM ,
+
−
−
+
+
+
+
+/−
CD5 , CD10 , CD19 , CD20 , CD22 , CD23 , CD25 , CD27 , HEAVY CHAIN DISEASES
−
+
−
19
FMC7 , CD103 , CD138 ). WM must be differentiated from
IgM MGUS, MM, chronic lymphocytic leukemia (CLL), and The HCDs are rare B-cell proliferative disorders characterized
mantle-cell lymphoma. by the production of an M-protein consisting of a portion of
the immunoglobulin heavy chain without a bound light chain.
Management and Prognosis Three types of HCD are recognized, based upon the class of
Many patients with WM are asymptomatic and can be observed immunoglobulin heavy chain produced by the malignant cell:
for months to years after the diagnosis is established before 1. Alpha HCD is a form of mucosa-associated lymphoreticular
requiring treatment. Asymptomatic patients with adequate tissue (MALT) lymphoma that is also called immuno-
hemoglobin and platelet levels are followed every 6 months with proliferative small intestinal disease (IPSID), Mediterranean
20
complete blood counts and monoclonal protein levels. Treatment lymphoma, or Seligmann disease.
is indicated in those who meet one or more of the conditions 2. Gamma HCD (Franklin disease) is typically associated with
presented in Table 80.5. 21 the presence of a systemic lymphoma, often of mixed
Symptomatic WM is treated with a regimen that incorporates lymphoid-plasmacytic character.
rituximab in combination with other agents. Symptomatic patients 3. Mu HCD has clinical features resembling small lymphocytic
with low tumor burden and minimally symptomatic patients lymphoma/CLL, often with distinctive vacuolated lymphocytes/
may be treated with the single agent rituximab. Patients who plasma cells in the bone marrow.
Clinical Presentation
The clinical presentation of the HCDs is that of a patient with
TABLE 80.5 Clinical and Laboratory a low-grade B-cell malignancy. Alpha HCD is a form of MALT
indications for initiation of treatment for lymphoma, with the same histological features of MALT-type
Waldenström Macroglobulinemia (WM) gastrointestinal lymphomas with marked plasma cell differentia-
Clinical indications for therapy initiation: tion. It is the most common form of HCD and occurs in patients
• Recurrent fever, night sweats, weight loss, fatigue from the Mediterranean region or Middle East, usually young
• Hyperviscosity males, and is often associated with relatively poor sanitation.
• Lymphadenopathy that is either symptomatic or bulky (≥5 cm in The gastrointestinal tract is most commonly involved in alpha
maximum diameter) HCD, resulting in abdominal pain, malabsorption with chronic
• Symptomatic hepatomegaly and/or splenomegaly diarrhea, steatorrhea, and loss of weight. Growth retardation,
• Symptomatic organomegaly and/or organ or tissue infiltration digital clubbing, and mesenteric lymphadenopathy may also be
• Peripheral neuropathy due to WM 23
present.
Laboratory indications for therapy initiation: Patients with gamma HCD typically present with systemic
• Symptomatic cryoglobulinemia symptoms, lymphadenopathy, splenomegaly, and/or anemia, and
• Cold agglutinin anemia occasionally with palatal and uvular swelling. The median age
• Immune hemolytic anemia and/or thrombocytopenia of patients with gamma HCD is 60 to 70 years, although the
• Nephropathy related to WM condition has been noted in persons younger than age 20.
• Amyloidosis related to WM Autoimmune manifestations are seen in about one-third of
• Hemoglobin ≤10 g/dL patients. 23
9
• Platelet count <100 × 10 /L
Mu HCD is the least common of the HCDs and has features
Source: Dimopoulos MA, Kastritis E, Owen RG, Kyle RA, Landgren O, Morra E, et al. resembling CLL/small lymphocytic lymphoma, although periph-
Treatment recommendations for patients with Waldenstrom macroglobulinemia (WM) eral adenopathy is less common than in CLL. Osteolytic lesions
and related disorders: IWWM-7 consensus. Blood 2014;124(9):1404–11. doi: 10.1182/ or pathological fractures occasionally have been reported in
blood-2014-03-565135. PubMed PMID: 25027391; PubMed Central PMCID:
PMC4148763. patients. Unlike those with alpha and gamma HCD, some patients
TABLE 80.6 Staging System for Waldenström Macroglobulinemia

Stage risk Characteristics Five-Year Survival Five-Year Progression-Free Survival
A Low B2M <3 mg/L and Hgb ≥12.0 g/dL 87% 83%
B Medium B2M <3 mg/L and Hgb <12.0 g/dL 63% 55%
C Medium B2M ≥3 mg/L and serum IgM ≥4.0 g/dL 53% 33%
D High B2M ≥3 mg/L and IgM <4.0 g/dL 21% 12%
B2M, Beta 2 microglobulin.
Source: Dhodapkar MV, Jacobson JL, Gertz MA, Rivkin SE, Roodman GD, Tuscano JM, et al. Prognostic factors and response to fludarabine therapy in patients with Waldenstrom
macroglobulinemia: results of United States intergroup trial (Southwest Oncology Group S9003). Blood 2001;98(1):41–8. PubMed PMID: 11418461.