Test Id : MSMRD

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.

This test should be ordered on patients treated for multiple myeloma to confirm remission has been achieved, as an annual follow-up of those in remission or in uncertain remission, or when MPCDS / mSMART, Plasma Cell Proliferative Disorder, FISH, Bone Marrow is desired.

1. Include patient's disease state (untreated, treated, monoclonal gammopathy of undetermined significance, stable).

2. Indicate if patient is on anti-CD38 therapy.

Specimen Type: Redirected bone marrow

Preferred: Yellow top (ACD solution A or B)

Acceptable: Lavender top (EDTA)

Specimen Volume: 4 mL

3 mL

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

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.

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.

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

The interpretation of results includes an overview of the results and the associated diagnostic, prognostic, and therapeutic implications.

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.

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

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)

Preanaltyical processing: Monday through Saturday

Results reported: Monday through Friday

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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.

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