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HelpTest Code MSMRD Myeloma Stratification and Risk-Adapted Therapy with Reflex to Minimal Residual Disease, Bone Marrow
Ordering Guidance
Necessary Information
1. Include patient's disease state (untreated, treated, monoclonal gammopathy of undetermined significance, stable).
2. Indicate if patient is on anti-CD38 therapy.
Specimen Required
Specimen Type: Redirected bone marrow
Preferred: Yellow top (ACD solution A or B)
Acceptable: Lavender top (EDTA)
Specimen Volume: 4 mL
Useful For
Risk stratification of patients with treated multiple myeloma, which can assist in determining treatment and management decisions
Risk stratification of patients with newly diagnosed multiple myeloma
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| CSMRT | MPCDS Pre-Analysis Cell Sorting, BM | No | No |
| MPCDS | mSMART Eval, PCPDs, FISH | Yes, (Order PCPDS) | No |
| MRDMR | Multiple Myeloma MRD by Flow, BM | Yes, (Order MRDMM) | No |
Testing Algorithm
Based on the flow cytometric analysis and the presence of greater than or equal to 0.1% monotypic plasma cells, pre-analysis cell sorting and fluorescence in situ hybridization for plasma cell proliferative disorders will be performed at an additional charge.
Based on the flow cytometric analysis and the absence of monotypic plasma cells, then minimal residual disease for multiple myeloma will be performed at an additional charge.
Method Name
Flow Cytometry/DNA Content/Cell Cycle Analysis
Reporting Name
mSMART with Reflex to MRD, BMSpecimen Type
Bone MarrowSpecimen Minimum Volume
3 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Bone Marrow | Ambient (preferred) | 72 hours | |
| Refrigerated | 72 hours |
Reject Due To
| Gross hemolysis | Reject |
| Fully clotted | Reject |
Clinical Information
Multiple myeloma is increasingly recognized as a disease characterized by marked cytogenetic, molecular, and proliferative heterogeneity. This heterogeneity is manifested clinically by varying degrees of disease aggressiveness. Multiple myeloma patients with more aggressive disease experience suboptimal responses to some therapeutic approaches; therefore, identifying these patients is critically important for selecting appropriate treatment options.
The Mayo algorithmic approach for stratification of myeloma and risk-adapted therapy classifies patients into either standard or high-risk categories based on the results of 2 assays: plasma cell proliferation and fluorescence in situ hybridization for specific multiple myeloma-associated abnormalities.
Reference Values
PLASMA CELL CLONALITY:
Normal bone marrow
No monotypic clonal plasma cells detected
DNA INDEX:
Normal polytypic plasma cells
DNA index (G0/G1 cells): Diploid 0.95-1.05
Interpretation
The interpretation of results includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.
Cautions
This test report is best used for patients treated for multiple myeloma to confirm remission has been achieved or as an annual follow-up of those in remission or in uncertain remission. It is designed for patients with multiple myeloma and may not be applicable for monoclonal gammopathy of uncertain significance, smoldering myeloma, or amyloidosis.
This stratification system is not meant to replace existing prognostic systems such as the International Staging System.
Method Description
Flow cytometric immunophenotyping of bone marrow is performed using the following antibodies: CD19, CD38, CD45, CD138, cytoplasmic kappa and lambda immunoglobulin, and DAPI (4',6-diamidino-2-phenylindole). Plasma cell clonality is detected through demonstrating CD38 and CD138 positivity along with immunoglobulin light chain restriction (ie, the presence of either predominately kappa or lambda immunoglobulin light chains) and abnormality of CD19 and/or CD45 expression. DNA index of clonal plasma cells and their proliferation activity is determined through staining of double-stranded DNA using DAPI.
Plasma cells (monoclonal/monotypic and polyclonal/polytypic) are detected by immunoglobulin light chain restriction, surface immunophenotype, and DNA content. If present, the light chain expressed by the monotypic plasma cells is indicated. The percentage of clonal plasma cells estimated by flow cytometry is affected by specimen processing and antigen loss with specimen aging. Manual differential counting remains the accepted standard for determining the bone marrow plasma cell percentage. The percentage of monotypic plasma cells in S-phase of the cell cycle is determined by quantitative DNA analysis. The DNA index is a calculated value. The presence of more than 1 value indicates the presence of cell populations with differing DNA contents within the monotypic plasma cells.(Dispenzieri A, Buadi F, Kumar SK, et al. Treatment of immunoglobulin light chain amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement. Mayo Clin Proc. 2015;90(8):1054–1081. doi:10.1016/j.mayocp.2015.06.009)
Plasma Cell Proliferative Disorder:
This test is performed using commercially available and laboratory-developed probes. Deletion or monosomy of chromosome 17, copy number gain of 1q, and additional copies of chromosomes 3, 7, 9, and 15 are detected using enumeration strategy probes. Translocations involving IGH are detected using dual-color, dual-fusion fluorescence in situ hybridization strategy probes. Rearrangement of IGH and MYC are detected using a break-apart strategy probe. For each probe set, 50 plasma cells (if possible) are scored and the result for each probe is reported. (Unpublished Mayo method)
Minimal Residual Disease:
Flow cytometric immunophenotyping for minimal residual disease of bone marrow is performed using the following antibodies:
Tube 1: CD138, CD27, CD38, CD56, CD45, CD19, CD117, and CD81.
Tube 2: CD138, CD27, CD38, CD56, CD45, CD19, cyKappa, and cyLambda.
Abnormal plasma cell populations are detected through demonstrating CD38 (multiepitope) and CD138 positivity along with immunoglobulin light chain restriction (ie, the presence of either predominately kappa or predominately lambda light chains) and abnormality of CD56, CD117, CD27, CD81, CD19 and/or CD45 expression. The percentage of clonal plasma cells estimated by flow cytometry is affected by specimen processing and antigen loss with specimen aging. Minimal residual disease reporting is affected by sample volume and cellularity.(Unpublished Mayo method)
Day(s) Performed
Preanaltyical processing: Monday through Saturday
Results reported: Monday through Friday
Report Available
1 to 13 daysSpecimen Retention Time
14 daysPerforming Laboratory
Mayo Clinic Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
88182-Flow cytometry, cell cycle or DNA analysis
88184-Flow cytometry; first cell surface, cytoplasmic or nuclear marker
88185 x 5-Flow cytometry; additional cell surface, cytoplasmic or nuclear marker (each)
88187-Flow cytometry interpretation, 2 to 8 Markers
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| MSMRD | mSMART with Reflex to MRD, BM | 93363-0 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| CK056 | Monotypic Plasma Cells: | 93362-2 |
| CK057 | Monotypic PC per Total Events | 93021-4 |
| CK058 | Monotypic Plasma Cells S-phase | 93361-4 |
| CK059 | Monotypic Plasma Cells DNA Index | 93360-6 |
| CK060 | Monotypic Plasma Cells DNA Ploidy | 93359-8 |
| CK061 | Polytypic PC per Total Events | 93358-0 |
| CK062 | Polytypic PC per All Plasma Cells | 93020-6 |
| 616032 | Final Diagnosis | 22637-3 |