1st order laboratory parameters – obligatory laboratory tests.
- Small blood count [normochromic anemia, leukopenia, and thrombocytopenia]
- Differential blood count
- Inflammatory parameters – CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate) [↑↑↑]
- Calcium [↑]
- Urine status (rapid test for: pH, leukocytes, nitrite, protein, blood), sediment, if necessary urine culture (pathogen detection and resistogram, that is, testing suitable antibiotics for sensitivity/resistance).
- Renal parameters – urea, creatinine, if necessary cystatin C or creatinine clearance [increase in renal retention parameters].
- 24-hour collection urine for determination of free light chains (in light chain myeloma).
- Beta-2-microglobulin (β2-microglobulin; marker protein of tubular reabsorption function).
- Total protein in blood serum; albumin.
- LDH
- Immunofixation electrophoresis in blood serum and urine – for detection and quantification.
- Quantitative immunoglobulin determination (IgA, IgD, IgE, IgG, IgM) and free κ- and λ-light chains in blood serum.
- Protein electrophoresis in blood serum (to detect the so-called M gradient).
- Quantitative kappa-lambda light chain determination [prerenal proteinuria/increased excretion of protein with urine].
- Serum free light chain (FLC) measurement (sFLC); more sensitive detection of the
- Light Chain Myeloma (LCMM) than with urine analyses of monoclonal protein.
- Therapy response and prognosis.
- Bone marrow diagnostics: cytology (examination of cells) and/or histology (fine tissue examination); cytogenetic studies (chromosome analysis and FISH) to detect unfavorable cytogenetic aberrations.
Laboratory parameters 2nd order – depending on the results of the history, physical examination and mandatory laboratory parameters – for differential diagnostic clarification.
- Bence-Jones proteins in the urine
- Differentiation of proteins in urine
- Uric acid
The diagnosis of plasmacytoma is based on the Ossermann criteria (three cardinal symptoms), two of which must be met:
- Appearance of monoclonal immunoglobulins in plasma and/or urine.
- Plasma cell nests in bone marrow and/or plasma cell percentage in bone marrow > 15%.
- Osteolytic foci in the bone or osteoporosis (bone loss) with simultaneous increase in plasma cells in the bone marrow or radiological evidence of osteolysis (bone loss).
Laboratory parameters 2nd order (follow-up/therapy control).
- CRP (C-reactive protein)
- LDH
- Immunoelectrophoresis (monoclonal immunoglobulins)
- Beta-2 microglobulin
Diagnostic criteria for the differential diagnosis of symptomatic multiple myeloma (MM) from “smouldering (asymptomatic) MM” and monoclonal gammopathy of uncertain significance (MGUS):
| MGUS* | Smouldering MM(smouldering myeloma) | Multiple myeloma (MM) | |
| Percentage of plasma monoclonal cells in bone marrow. | < 10 % | ≥ 10 % | > 10 % or plasmocytoma |
| Serum M protein | <30 g/l in serum | ≥ 30 g/l OR | present in serum and/or urine |
| Urine M protein | <500 mg/24 h | ≥ 500 mg/24 h | |
| CRAB criteria (see below). | No CRAB criterion | No CRAB criterion | ≥1 CRAB criterionODER |
| ≥ 1 SLiM criterion |
* A MGUS (see below) progresses to a plasmacytoma in approximately 1% of cases. Legend
- MGUS: monoclonal gammopathy of uncertain significance.
- CRAB: see table below
- M protein: monoclonal protein
- SLiM criterion: see table below.
In diagnostically confirmed MM, myeloma treatment is indicated if any of the following CRAB criteria are met; the acronym CRAB stands for:
| Hypercalcemia | C (hypercalcaemia) | Serum calcium > 0.25 mmol/L above the upper normal range or > 2.75 mmol/L (> 11 mg/dL) |
| Renal insufficiency | R (renal failure) | GFR (glomerular filtration rate) <40 mL/min or serum creatinine >177 µmol/L. |
| Anemia | A (anemina) | > 2.0 g/dL below the lower normal range or < 10 g/dL |
| Bone lesions(osteolysis and/or osteoporosis). | B (bone lesions) | ≥ 1 lesion by radiography, CT, or PET-CT. |
The acronym SLiM stands for:
| Sixty | 60% monoclonal plasma cells in bone marrow |
| Light chain | Ratio of involved free light chain to uninvolved free light chain ≥ 100, where the concentration of involved free light chain must be ≥ 100 mg/l. |
| MRI | More than one focal lesion of at least 5 millimeters in size on whole-body MRI in the absence of a bone lesion |
Criteria of relapsed myeloma are:
| Clinical criteria of recurrence | New-onset soft tissue plasmacytoma or osteolysis |
| Hypercalcemia (≥ 11.5 mg/dl; 2.875 mmol/l) | |
| Increase in serum creatinine of ≥ 2 mg/dl (myeloma-related). | |
| Drop in hemoglobin of ≥ 2 g/dl, myeloma-related. | |
| Increase in size (≥50%) of preexisting plasmacytomas or osteolysis | |
| Hyperviscosity requiring therapy. | |
| Significant biochemical recurrence in patients not meeting clinical recurrence criteria | Doubling of M protein in two consecutive measurements two months apart, with a reference value of 5 g/l, and/or ≥ 25% increase in urine or absolute ≥ 200 mg/24 h |
In two consecutive measurements, one of the following increases:
|
More hints
- Monoclonal gammopathy of uncertain significance (MGUS) – precancerous condition for lymphoproliferative disorders such as multiple myeloma or Waldenström’s disease; paraproteinemia with monoclonal IgM globulins without histologic infiltration of the bone marrow with plasma cells or lymphoma cells (i.e., there is no plasmacytoma/multiple myeloma or Waldenström’s disease); in the United States, monoclonal gammopathy of unclear significance (MGUS) is found in 3.2% of those over 50 years of age and 5.3% of those over 70 years of age; progresses to lymphoproliferative disease in 1.5% of cases per yearNote: MGUS may persist for more than 30 years before clinical disease develops; in these patients, an additional jag, the “M gradient,” can be seen in the gamma globulin region. This indicates the spread of cell clones in the bone marrow.
