Test Id : MSMRD
Myeloma Stratification and Risk-Adapted Therapy with Reflex to Minimal Residual Disease, Bone Marrow
Useful For
Suggests clinical disorders or settings where the test may be helpful
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
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| MPCDB | Probe, Each Additional (MPCDS) | No, (Bill Only) | No |
| 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
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
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
A short description of the method used to perform the test
Flow Cytometry/DNA Content/Cell Cycle Analysis
NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
Aliases
Lists additional common names for a test, as an aid in searching
+1q or CKS1B
+3/+7
+9/+15
-13 (monosomy 13)
13q- / -13 (13q deletion) or RB1
17p- (17p deletion) or TP53
IGH (14q32) rearrangement
Labeling Index
Monoclonal Gammopathy of Unknown Significance (MGUS)
Multiple Myeloma
MYC (8q24.1) rearrangement
Myeloma Staging
PC Proliferation
PCLIP
Plasma Cell Labeling Index (PCLI)
Plasma Cell Leukemia
Plasma Cell Staging
t(11;14)-CCND1/IGH
t(14;16)-IGH/MAF
t(14;20)-IGH/MAFB
t(4;14)-FGFR3/IGH
t(6;14)-CCND3/IGH
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
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.
Specimen Type
Describes the specimen type validated for testing
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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing
Specimen Type: Redirected bone marrow
Preferred: Yellow top (ACD solution A or B)
Acceptable: Lavender top (EDTA)
Specimen Volume: 4 mL
Forms
If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.
Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.
3 mL
Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected
| Gross hemolysis | Reject |
| Fully clotted | Reject |
Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Bone Marrow | Ambient (preferred) | 72 hours | |
| Refrigerated | 72 hours |
Useful For
Suggests clinical disorders or settings where the test may be helpful
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
Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.
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.
Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
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
Provides information to assist in interpretation of the test results
The interpretation of results includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.
Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
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.
Clinical Reference
Recommendations for in-depth reading of a clinical nature
1. Gonsalves WI, Buadi FK, Ailawadhi S, et al. Utilization of hematopoietic stem cell transplantation for the treatment of multiple myeloma: a Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus statement. Bone Marrow Transplant. 2019;54(3):353-367. doi:10.1038/s41409-018-0264-8
2. Kapoor P, Ansell SM, Fonseca R, et al. Diagnosis and management of waldenstrom macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) guidelines 2016. JAMA Oncol. 2017;3(9):1257-1265. doi:10.1001/jamaoncol.2016.5763
3. Mikhael JR, Dingli D, Roy V, et al. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013;88(4):360-376. doi:10.1016/j.mayocp.2013.01.019.
4. Swerdlow S, Campo E, Harris NL, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. IARC Press; 2017. WHO Classification of Tumours, Vol. 2
5. Kumar SK, Rajkumar SV. The multiple myelomas-current concepts in cytogenetic classification and therapy. Nat Rev Clin Oncol. 2018;15(7):409-421 doi:10.1038/s41571-018-0018-y
6. Rajkumar SV, Landgren O, Mateos MV. Smoldering multiple myeloma. Blood. 2015;125(20):3069-3075 doi:10.1182/blood-2014-09-568899
7. Aljama MA, Sidiqi MH, Lakshman A, et al. Plasma cell proliferative index is an independent predictor of progression in smoldering multiple myeloma. Blood Adv. 2018;2(22):3149-3154
8. Mellors PW, Binder M, Ketterling RP, et al. Metaphase cytogenetics and plasma cell proliferation index for risk stratification in newly diagnosed multiple myeloma. Blood Adv. 2020;4(10):2236-2244
9. Sidana S, Jevremovic D, Ketterling RP, et al. Rapid assessment of hyperdiploidy in plasma cell disorders using a novel multi-parametric flow cytometry method. Am J Hematol. 2019;94(4):424-430
10. Ghosh T, Gonsalves WI, Jevremovic D, et al. The prognostic significance of polyclonal bone marrow plasma cells in patients with relapsing multiple myeloma. Am J Hematol. 2017;92(9):E507-E512
Method Description
Describes how the test is performed and provides a method-specific reference
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)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.
Preanaltyical processing: Monday through Saturday
Results reported: Monday through Friday
Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.
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- Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
- Prospective clients should contact their account representative. For assistance, contact Customer Service.
Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.
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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
CPT codes are provided by the performing laboratory.
CPT codes are provided by the performing laboratory.
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® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| 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
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 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 |