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“CRAB” Crawls Into Importance
By Brian G.M. Durie, M.D.
07.26.03

The IMF Scientific Advisors recently developed new diagnostic criteria for myeloma, which were published in the British Journal of Haematology (Kyle, et al. 2003). Table 1 shows the criteria for multiple myeloma. As compared to many prior definitions, this emphasizes the clinical features of progressive disease associated with active myeloma and identified as "CRAB" features. The intent is to distinguish between active myeloma and the precursor states MGUS (Table 2) and smoldering/indolent myeloma (Table 3). These precursor states typically do not require systemic anti-myeloma therapy. However, there are two important caveats to the new criteria.

  1. "CRAB" features must be myeloma related - Many medical conditions can result in calcium elevation, renal insufficiency, anemia and bone abnormalities. It is therefore critically important to assess that these "CRAB" features are a direct result of myeloma progression. This may require additional testing to, for example, rule out hyperparathyroidism (a hormone abnormality) as a cause of increased calcium; kidney biopsy to exclude other causes of kidney abnormality; blood and/or other studies to exclude other causes of anemia from, for example, sickle cell disease to iron or vitamin deficiency or other bone marrow problems; and scans or other tests to assess bone abnormalities. These kinds of tests are particularly important if a patient has no symptoms or only a few symptoms and/or if it is not clear how progressive the myeloma really is. If the diagnosis is truly in doubt, this may be an appropriate situation for specialty consultation.

  2. MGUS and smoldering myeloma can sometimes require treatment - Typically MGUS and smoldering myeloma do not require systemic treatment. However, that is not always the case. The best example is one in which a patient basically has MGUS, but the myeloma protein is toxic in some way, such as causing neuropathy or blood clotting or bleeding problems. In such cases, although the MGUS is not an active cancer, there can be major medical problems, which require urgent treatment. In such cases, "anti-myeloma" treatment is used including often steroids, cytoxan, intravenous gammaglobin plasmapheresis and even stem cell transplantation.

With these caveats, it is hoped that focusing upon CRAB as an identifier for active myeloma the selection of patients for anti-myeloma therapy can be significantly improved. These and related issues are discussed in the "Myeloma Management Guidelines" a Consensus Report from the Scientific Advisors of the IMF (Durie, et al. 2003) soon to be published in the European Journal of Hematology.

TABLE 1
MULTIPLE MYELOMA

DIAGNOSTIC CRITERIA: ALL 3 REQUIRED

  1. Monoclonal plasma cells in the bone marrow > 10% and/or presence of a biopsy-proven plasmacytoma

  2. Monoclonal protein present in the serum and/or urine *

  3. Myeloma-related organ dysfunction (1 or more) **
    • [C] Calcium elevation in the blood S. Calcium >10.5 mg/l or upper limit of normal{}
    • [R] Renal insufficiency S. Creatinine > 2 mg/dl{}
    • [A] Anemia Hemoglobin < 10 g/dl or 2 g < normal{}
    • [B] Lytic bone lesions or osteoporosis ***

NOTE: THESE CRITERIA IDENTIFY STAGE IB and STAGES II and III A/B MYELOMA BY DURIE/SALMON STAGE. Stage IA becomes smoldering or indolent myeloma (Table 3).


* If no monoclonal protein is detected (non-secretory disease), then > 30% monoclonal bone marrow plasma cells and/or a biopsy-proven plasmacytoma required.

** A variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy. Such dysfunction is sufficient to support classification of myeloma if proven to be myeloma related.

*** If a solitary (biopsy-proven) plasmacytoma or osteoporosis alone (without fractures) are the sole defining criteria, then > 30% plasma cells are required in the bone marrow.

TABLE 2
MGUS: MONOCLONAL GAMMOPATHY
of UNDETERMINED SIGNIFICANCE

DIAGNOSTIC CRITERIA: ALL 3 REQUIRED

  1. Serum Monoclonal protein and/or urine monoclonal protein level low*

  2. Monoclonal bone marrow plasma cells < 10%

  3. Normal serum calcium, hemoglobin level and serum creatinine.

    • No bone lesions on full skeletal x-ray survey and/or other imaging if performed.

    • No clinical or laboratory features of amyloidosis or light chain depostion disease.


* Low is defined as:

  • Serum IgG < 3.5 g/dl
  • Serum IgA < 2.0 g/dl
  • Urine monoclonal kappa or lambda < 1.0 g/24 hours

TABLE 3
SMOLDERING OR INDOLENT MYELOMA

DIAGNOSTIC CRITERIA: ALL 3 REQUIRED

  1. Monoclonal protein present in the serum and/or urine

  2. Monoclonal plasma cells present in the bone marrow and/or a tissue biopsy

  3. Not meeting criteria for MGUS, multiple myeloma, or solitary plasmacytoma of bone

NOTE: THESE CRITERIA IDENTIFY STAGE IA MYELOMA BY DURIE/SALMON STAGE.



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