Table 1 Disease definitions for the... | American Society of Hematology

Table 1

Disease definitions for the monoclonal gammopathies: MGUS and related disorders

Type of monoclonal gammopathy	Premalignancy with a low risk of progression (1%-2% per year)	Premalignancy with a high risk of progression (10% per year)	Malignancy
IgG and IgA (non-IgM) monoclonal gammopathies*	Non-IgM MGUS	Smoldering multiple myeloma	Multiple myeloma
	All 3 criteria must be met: Serum monoclonal protein < 3 g/dL Clonal bone marrow plasma cells < 10%, and Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to the plasma cell proliferative disorder	Both criteria must be met: Serum monoclonal protein (IgG or IgA) ≥ 3 g/dL and/or clonal bone marrow plasma cells ≥ 10%, and Absence of end-organ damage such as lytic bone lesions, anemia, hypercalcemia, or renal failure that can be attributed to a plasma cell proliferative disorder	All 3 criteria must be met except as noted: Clonal bone marrow plasma cells ≥ 10% Presence of serum and/or urinary monoclonal protein (except in patients with true nonsecretory multiple myeloma), and Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically Hypercalcemia: serum calcium > 11.5 mg/dL or Renal insufficiency: serum creatinine > 2 mg/dL or estimated creatinine clearance < 40 mL/min Anemia: normochromic, normocytic with a hemoglobin value of > 2 g/dL below the lower limit of normal or a hemoglobin value < 10 g/dL Bone lesions: lytic lesions or severe osteopenia attributed to a plasma cell proliferative disorder or pathologic fractures
IgM monoclonal gammopathies	IgM MGUS†	Smoldering Waldenström macroglobulinemia	Waldenström macroglobulinemia
	All 3 criteria must be met: Serum monoclonal protein < 3 g/dL Clonal bone marrow lymphoplasmacytic cells < 10%, and Absence of end-organ damage such as anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder	Both criteria must be met: Serum IgM monoclonal protein ≥ 3 g/dL and/or bone marrow lymphoplasmacytic infiltration ≥ 10%, and No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder	All criteria must be met: IgM monoclonal gammopathy (regardless of the size of the M-protein), and ≥ 10% bone marrow lymphoplasmacytic infiltration (usually intertrabecular) by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation and a typical immunophenotype (eg, surface IgM⁺, CD5^+/−, CD10⁻, CD19⁺, CD20⁺, CD23⁻) that satisfactorily excludes other lymphoproliferative disorders including chronic lymphocytic leukemia and mantle cell lymphoma Evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder.
			IgM myeloma
			All criteria must be met: Symptomatic monoclonal plasma cell proliferative disorder characterized by a serum IgM monoclonal protein regardless of size Presence of 10% plasma cells on bone marrow biopsy Presence of lytic bone lesions related to the underlying plasma cell disorder and/or translocation t(11;14) on fluorescence in situ hybridization.
Light-chain monoclonal gammopathies	Light-chain MGUS	Idiopathic Bence Jones proteinuria	Light-chain multiple myeloma†
	All criteria must be met: Abnormal FLC ratio (< 0.26 or > 1.65) Increased level of the appropriate involved light-chain (increased kappa FLC in patients with ratio > 1.65 and increased lambda FLC in patients with ratio < 0.26) No immunoglobulin heavy-chain expression on immunofixation Clonal bone marrow plasma cells < 10%, and Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to the plasma cell proliferative disorder	All criteria must be met: Urinary monoclonal protein on urine protein electrophoresis ≥ 500 mg/24 h and/or clonal bone marrow plasma cells ≥ 10% No immunoglobulin heavy-chain expression on immunofixation Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to the plasma cell proliferative disorder	Same as multiple myeloma except no evidence of immunoglobulin heavy-chain expression

Type of monoclonal gammopathy	Premalignancy with a low risk of progression (1%-2% per year)	Premalignancy with a high risk of progression (10% per year)	Malignancy
IgG and IgA (non-IgM) monoclonal gammopathies*	Non-IgM MGUS	Smoldering multiple myeloma	Multiple myeloma
	All 3 criteria must be met: Serum monoclonal protein < 3 g/dL Clonal bone marrow plasma cells < 10%, and Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to the plasma cell proliferative disorder	Both criteria must be met: Serum monoclonal protein (IgG or IgA) ≥ 3 g/dL and/or clonal bone marrow plasma cells ≥ 10%, and Absence of end-organ damage such as lytic bone lesions, anemia, hypercalcemia, or renal failure that can be attributed to a plasma cell proliferative disorder	All 3 criteria must be met except as noted: Clonal bone marrow plasma cells ≥ 10% Presence of serum and/or urinary monoclonal protein (except in patients with true nonsecretory multiple myeloma), and Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically Hypercalcemia: serum calcium > 11.5 mg/dL or Renal insufficiency: serum creatinine > 2 mg/dL or estimated creatinine clearance < 40 mL/min Anemia: normochromic, normocytic with a hemoglobin value of > 2 g/dL below the lower limit of normal or a hemoglobin value < 10 g/dL Bone lesions: lytic lesions or severe osteopenia attributed to a plasma cell proliferative disorder or pathologic fractures
IgM monoclonal gammopathies	IgM MGUS†	Smoldering Waldenström macroglobulinemia	Waldenström macroglobulinemia
	All 3 criteria must be met: Serum monoclonal protein < 3 g/dL Clonal bone marrow lymphoplasmacytic cells < 10%, and Absence of end-organ damage such as anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder	Both criteria must be met: Serum IgM monoclonal protein ≥ 3 g/dL and/or bone marrow lymphoplasmacytic infiltration ≥ 10%, and No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder	All criteria must be met: IgM monoclonal gammopathy (regardless of the size of the M-protein), and ≥ 10% bone marrow lymphoplasmacytic infiltration (usually intertrabecular) by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation and a typical immunophenotype (eg, surface IgM⁺, CD5^+/−, CD10⁻, CD19⁺, CD20⁺, CD23⁻) that satisfactorily excludes other lymphoproliferative disorders including chronic lymphocytic leukemia and mantle cell lymphoma Evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, or hepatosplenomegaly that can be attributed to the underlying lymphoproliferative disorder.
			IgM myeloma
			All criteria must be met: Symptomatic monoclonal plasma cell proliferative disorder characterized by a serum IgM monoclonal protein regardless of size Presence of 10% plasma cells on bone marrow biopsy Presence of lytic bone lesions related to the underlying plasma cell disorder and/or translocation t(11;14) on fluorescence in situ hybridization.
Light-chain monoclonal gammopathies	Light-chain MGUS	Idiopathic Bence Jones proteinuria	Light-chain multiple myeloma†
	All criteria must be met: Abnormal FLC ratio (< 0.26 or > 1.65) Increased level of the appropriate involved light-chain (increased kappa FLC in patients with ratio > 1.65 and increased lambda FLC in patients with ratio < 0.26) No immunoglobulin heavy-chain expression on immunofixation Clonal bone marrow plasma cells < 10%, and Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to the plasma cell proliferative disorder	All criteria must be met: Urinary monoclonal protein on urine protein electrophoresis ≥ 500 mg/24 h and/or clonal bone marrow plasma cells ≥ 10% No immunoglobulin heavy-chain expression on immunofixation Absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) that can be attributed to the plasma cell proliferative disorder	Same as multiple myeloma except no evidence of immunoglobulin heavy-chain expression

MGUS indicates monoclonal gammopathy of undetermined significance; and FLC, free light chain.

Occasionally patients with IgD and IgE monoclonal gammopathies have been described and will be considered to be part of this category as well.

†

Note that conventionally IgM MGUS is considered a subtype of MGUS, and similarly light-chain multiple myeloma is considered as a subtype of multiple myeloma. Unless specifically distinguished, when the terms MGUS and multiple myeloma are used in general, they include IgM MGUS and light-chain multiple myeloma, respectively. (Reprinted with permission.¹³)

View Large

This Feature Is Available To Subscribers Only