The Importance of Complementary Immunological Markers in the Diagnosis of Minimal Residual Disease in Multiple Myeloma

EE Tolstykh1, OS Chuvadar2, AA Semenova1, NA Kupryshina1, OP Kolbatskaya1, YuI Klyuchagina1, OA Kolomeitsev1, GS Tumyan1, NN Tupitsyn1

1 NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 Center of Clinical Oncology and Hematology, 4a Semashko ul., Simferopol, Republic of Crimea, Russian Federation, 295026

For correspondence: Prof. Nikolai Nikolaevich Tupitsyn, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(925)537-15-82; e-mail: nntca@yahoo.com

For citation: Tolstykh EE, Chuvadar OS, Semenova AA, et al. The Importance of Complementary Immunological Markers in the Diagnosis of Minimal Residual Disease in Multiple Myeloma. Clinical oncohematology. 2022;15(4):388–95. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-388-395


ABSTRACT

Background. The population of non-tumor plasma cells in healthy subjects’ bone marrow is known to be fairly heterogeneous. Among them, there may be a small number of CD19–, CD56+, CD45– plasma cells which differ from the main bulk of the normal plasmacytic cells by the lack of CD19 and CD45 expression and the presence of CD56 expression. It is the fact which makes the monitoring of minimal residual disease (MRD) especially challenging in multiple myeloma (MM) since normal and aberrant plasma cells should be compared. For this reason, a study of such complementary diagnostic markers as CD27, CD28, CD117, and CD81 is extremely important.

Aim. To analyze the role of complementary diagnostic markers (CD27, CD28, CD117, and CD81) of MRD in MM patients at different disease stages.

Materials & Methods. The present study enrolled 62 MM patients aged 31–76 years (median 58 years); 25 women and 37 men. The analysis focused on morphological and immunophenotypic properties of bone marrow plasma cells. MRD was detected by 8-color flow cytometry with the use of FACSCanto II Flow Cytometer (USA) based on EuroFlow standards.

Results. At the stage of primary diagnosis of MM, the immunophenotype of plasma cells was analyzed in all 62 patients using two 8-color panels recommended by the EuroFlow Consortium (2012). In accordance with primary immunophenotyping data, MRD was evaluated on the basis of not only the main diagnostic markers of plasma cells (CD38, CD138, CD45, CD56, and CD19), but also the complementary ones, such as CD27, CD28, CD117, and CD81. The study was basically conducted after induction therapy and upon remission. With cut-off > 0.01 % of aberrant plasma cells, the MRD incidence was the following: 91.0 % with CD27, 90.6 % with CD28, 87.0 % with CD117, and 96.7 % with CD81 markers. Respectively, no MRD was detected in 9.0 % with CD27, 9.4 % with CD28, 13.0 % with CD117, and 3.3 % with CD81 markers.

Conclusion. Using the set of complementary markers including CD27, CD28, CD117, and CD81 allows to establish a more accurate MRD status in MM, i.e. either negative or positive one, taking into account the expression of basic antigens CD38, CD138, CD45, CD56, and CD19.

Keywords: multiple myeloma, minimal residual disease, plasma cells, bone marrow, multicolor flow cytometry.

Received: March 2, 2022

Accepted: August 30, 2022

Read in PDF

Статистика Plumx английский

REFERENCES

  1. Swerdlow SH, Campo E, Harris NL, et al. (eds) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th edition. Lyon: IARC Press; 2017.
  2. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–e548. doi: 10.1016/S1470-2045(14)70442-5.
  3. Злокачественные новообразования в России в 2019 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена — филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2020. 252 с.
    [Kaprin AD, Starinskii VV, Shakhzadova AO, eds. Zlokachestvennye novoobrazovaniya v Rossii v 2019 godu (zabolevaemost’ i smertnost’). (Malignant neoplasms in Russia in 2019 (incidence and mortality.) Moscow: MNIOI im. P.A. Gertsena — filial FGBU “NMITs radiologii” Publ.; 252 p. (In Russ)]
  4. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Буки Веди, 2018. 324 с.
    [Poddubnaya IV, Savchenko VG, eds. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Russian clinical guidelines on diagnosis and treatment of lymphoproliferative disorders.) Moscow: Buki Vedi Publ.; 2018. 324 р. (In Russ)]
  5. van Dongen JJ, Lhermitte L, Bottcher S, et al. EuroFlow antibody panels for standardized n-dimentional flow cytometric immunophenotyling of normal, reactive and malignant leukocytes. Leukemia. 2012;26(9):1908–75. doi: 10.1038/leu.2012.120.
  6. Flores-Montero J, de Tute R, Paiva B, et al. Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications or MRD detection in multiple myeloma. Cytometry B Clin Cytom. 2016;90(1):61–72. doi: 10.1002/cyto.b.21265.
  7. Mateo G, Montalban MA, Vidriales MB, et al. Prognostic value of immunophenotyping in multiple myeloma: a study by the PETHEMA/GEM cooperative study groups on patients uniformly treated with high-dose therapy. J Clin Oncol. 2008;26(16):2737–44. doi: 10.1200/JCO.2007.15.4120.
  8. Chen F, Hu Y, Wang X, et al. Expression of CD81 and CD117 in plasma cell myeloma and the relationship to prognosis. Cancer Med. 2018;7(12):5920–7. doi: 10.1002/cam4.1840.