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1796 Part XI: Malignant Lymphoid Diseases Chapter 109: Macroglobulinemia 1797

of tumor-cell killing with some agents. By way of example, rituximab Other cytopenias also may be significant predictors of survival. The
193
can induce a flare in serum IgM levels, whereas everolimus, bortezomib, precise level of cytopenias with prognostic significance has not been
and ibrutinib can suppress IgM levels independent of tumor-cell killing determined. Some series have identified a platelet count of less than 100
9
9
in some patients, a finding referred to as IgM discordance. 158,159,162,181,183,189 to 150 × 10 /L and a granulocyte count of less than 1.5 × 10 /L as inde-
Moreover, with selective B-cell–depleting agents such as rituximab and pendent prognostic factors. 193,194 The number of cytopenias in a given
alemtuzumab, residual IgM-producing plasma cells are spared and con- patient has been proposed as a prognostic factor. Serum albumin lev-
193
tinue to persist, thus potentially skewing the relative response and assess- els also correlate with survival in WM patients in some studies, using
190
ment to treatment. sCD27 levels have been investigated as an alternative multivariate analyses. 193,195 Elevated serum β -microglobulin levels (>3.0
2
surrogate marker in WM given their correlation with WM disease burden, to 3.5 g/dL) have also shown strong prognostic correlation in WM. 193–196
and may remain a faithful marker of disease in patients experiencing a Several scoring systems have been proposed based on these analyses
rituximab-related IgM flare, as well as after plasmapheresis. 59,191 The use of (Table 109–4), including the WM International Prognostic Scoring Sys-
quantitative allele-specific PCR assays to assess serial MYD88 L265P burden tem (WM IPSS) which incorporates five adverse covariates: advanced
in WM patients is also under investigation. 36,38 age (>65 years), hemoglobin less than or equal to 11.5 g/dL, platelet
9
count less than or equal to 100 × 10 /L, β -microglobulin greater than
2
COURSE AND PROGNOSIS 3 mg/L, and serum monoclonal protein concentration greater than 7 g/
dL. Among 537 WM patients evaluated in the development of WM
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WM typically presents as an indolent disease. The presence of 6q dele- IPSS, low-risk patients (27 percent) presented with none or one of the
tions may have prognostic significance, although this is disputed. 20,21 adverse characteristics and advanced age, intermediate-risk patients
Age is an important prognostic factor (>65 years), 192–194 but is influ- (38 percent) with two adverse characteristics or only advanced age, and
enced by comorbidities. Anemia that reflects both marrow involve- high-risk patients (35 percent) with more than two adverse characteris-
ment and the serum level of the IgM monoclonal protein (because of tics. Five-year survival rates for these patients were 87 percent, 68 per-
the impact of IgM on intravascular fluid retention) has emerged as a cent, and 36 percent, respectively. Importantly, the WM IPSS retained
strong adverse prognostic factor with hemoglobin levels of less than its prognostic significance in subgroups defined by age, treatment
9 to 12 g/dL associated with decreased survival in several series. 192–194 with alkylating agent and nucleoside analogues. Recent data from the

TABLE 109–4. Prognostic Scoring Systems in Waldenström Macroglobulinemia
Study Adverse Prognostic Factors Number of Groups Survival
Gobbi and colleagues 185 Hgb <9 g/dL 0–1 prognostic factors Median: 48 months
Age >70 years 2–4 prognostic factors Median: 80 months
Weight loss
Cryoglobulinemia
Morel and colleagues 186 Age ≥65 years 0–1 prognostic factors 5 year: 87% of patients
Albumin <4 g/dL 2 prognostic factors 5 year: 62%
Number of cytopenias: 3–4 prognostic factors 5 year: 25%
Hgb <12 g/dL
Platelets <150 × 10 /L
9
WBC <4 × 10 /L
9
Dhodapkar and colleagues 187 β M ≥3 g/dL β M <3 mg/dL + Hgb ≥12 g/dL 5 year: 87% of patients
2 2
Hgb <12 g/dL β M <3 mg/dL + Hgb <12 g/dL 5 year: 63%
2
IgM <4 g/dL β M ≥3 mg/dL + IgM ≥4 g/dL 5 year: 53%
2
β M ≥3 mg/dL + IgM <4 g/dL 5 year: 21%
2
Application of International Albumin ≤3.5 g/dL Albumin ≥3.5 g/dL + β M <3.5 mg/dL Median: NR
2
Staging System Criteria for β M ≥3.5 mg/L Albumin ≤3.5 g/dL + β M <3.5 or Median: 116 months
Myeloma to WM Dimopoulos 2 2
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and colleagues β M 3.5–5.5 mg/dL Median: 54 months
2
β M >5.5 mg/dL
2
International Prognostic Age >65 year 0–1 prognostic factors (excluding age) 5 year: 87% of patients
Scoring System for WM Morel Hgb <11.5 g/dL 2 prognostic factors (or age >65 years) 5 year: 68%
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and colleagues
9
Platelets <100 × 10 /L 3–5 prognostic factors 5 year: 36%
β M >3 mg/L
2
IgM >7 g/dL
β M, β -microbloulin; Hgb, hemoglobulin; NR, not reported; WBC, white blood cell count.
2 2

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