Immunological features of the bone marrow microenvironment and assessment of bone marrow lesions in patients with classical Hodgkin lymphoma

Background. The study of bone marrow involvement is a necessary step in disease staging, both in non-Hodgkin lymphomas and in the case of Hodgkin lymphoma (HL). The standard assessment of bone marrow lesion is carried out based on immunohistochemical examination of bone marrow trepanobioptate, and recently computer technologies (positron emission tomography combined with computed tomography) have been introduced to assess bone marrow involvement. At the same time, immunological methods for detecting tumor cells using multicolor flow cytometry are more available. In addition, they allow for detailed study of the tumor bone marrow microenvironment.

Aim. To evaluate the immunomorphological features of bone marrow in HL and the possibility of identifying specific bone marrow lesions using flow cytometry.

Materials and methods. The study included the analysis of 107 bone marrow samples. The samples were obtained from 107 patients with various variants of classical HL, diagnosed and treated at the Lapino Clinical Hospital and the P.A. Herzen Moscow State Medical Institute from 2018 to 2022.

Results. The features of bone marrow lymphocytes subpopulation in patients with classical HL are shown.

Conclusion. An immunological assessment of bone marrow involvement degree was carried out, data from flow cytometry and immunohistochemical examination of trephine biopsy specimens during primary diagnosis were compared, and the features of bone marrow lymphocytes subpopulation were evaluated. The interrelation of these factors at the diagnostic stage in classical variants of HL was studied. At the end of treatment, the primary immunological data (the degree of bone marrow involvement) were compared with the results of the positron emission tomography combined with computed tomography.

1. Aggarwal P., Limaiem F. Reed Sternberg Cells. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2022.

2. Weiler-Sagie M., Kagna O., Dann E.J. et al. Characterizing bone marrow involvement in Hodgkin’s lymphoma by FDG-PET/CT. Eur J Nucl Med Mol Imaging 2014;41(6):1133–40. DOI: 10.1007/s00259-014-2706-x

3. Azambuja D., Natkunam Y., Biasoli I. et al. Lack of association of tumor-associated macrophages with clinical outcome in patients with classical Hodgkin’s lymphoma. Ann Oncol 2012;23(3):736–42. DOI: 10.1093/annonc/mdr15

4. Ferrarini I., Bernardelli A., Lovato E. et al. An updated portrait of monocyte-macrophages in classical Hodgkin lymphoma. Front Oncol 2023;13:1149616. DOI: 10.3389/fonc.2023.1149616

5. Steidl C., Farinha P., Gascoyne R.D. Macrophages predict treatment outcome in Hodgkin’s lymphoma. Haematologica 2011;96(2):186–9. DOI: 10.3324/haematol.2010.033316

6. Jitani A.K., Dutta S., Mandal P.K. et al. Utility of 18F-fluorodeoxyglucose PET-CT scan in detecting bone marrow involvement in lymphoma. Indian J Med Res 2021;154(5):691–8. DOI: 10.4103/ijmr.IJMR_1420_19

7. Lakhwani S., Cabello-García D., Allende-Riera A. et al. Bone marrow trephine biopsy in Hodgkin’s lymphoma. Comparison with PET-CT scan in 65 patients. Med Clin (Barc) 2018;9(150):104–6. DOI: 10.1016/j.medcli.2017.06.060

8. Mato A.R., Wierda W.G., Davids M.S. et al. Utility of positron emission tomography-computed tomography in patients with chronic lymphocytic leukemia following B-cell receptor pathway inhibitor therapy. Haematologica 2019;104(11):2258–64. DOI: 10.3324/haematol.2018.207068

9. Tezol Ö., Sağcan F., Özcan P.P. et al. Bone marrow involvement in pediatric malignancies: a comparison study of Positron emission tomographycomputed tomography and bone marrow biopsy. J Pediatr 2020;62(2):182–90. DOI: 10.24953/turkjped.2020.02.003

10. Agostinelli C. How can we better predict treatment outcomes in classical Hodgkin’s lymphoma? Int J Hematol Oncol 2017;6(3):65–8. DOI: 10.2217/ijh-2017-0010

11. Grivtsova L.Yu., Mushkarina T.Yu., Lunin V.V., Zeynalova P.A. Flow cytometry in the diagnosis of plasma cell tumors and assessment of minimal residual disease. Onkogematologiya = Oncohematology 2021;16(3):16–25. (In Russ.). DOI: 10.17650/1818-8346-2021-16-3-16-25

12. Grivtsova L.Yu., Lunin V.V., Semenova A.A. et al. Minimal residual disease in plasma cell (multiple) myeloma: flow cytometric approaches. Onkogematologiya = Oncohematology 2020;15(1): 40–50. (In Russ.). DOI: 10.17650/1818-8346-2020-15-1-40-50

13. Fromm J.R., Wood B.L. A six-color flow cytometry assay for immunophenotyping classical Hodgkin lymphoma in lymph nodes. Am J Clin Pathol 2014;141(3):388–96. DOI: 10.1007/s00277-012-1608-x

14. Fromm J.R., Thomas A., Wood B.L. Characterization and purification of neoplastic cells of nodular lymphocyte predominant Hodgkin lymphoma from lymph nodes by flow cytometry and flow cytometric cell sorting. Am J Pathol 2017;187(2):304–17. DOI: 10.1016/j.ajpath.2016.10.007

15. Fromm J.R., Thomas A., Wood B.L. Flow cytometry can diagnose classical Hodgkin lymphoma in lymph nodes with high sensitivity and specificity. Am J Clin Pathol 2009;131(3):322–32. DOI: 10.1309/AJCPW3UN9DYLDSPB

16. Fromm J.R., Kussick S.J., Wood B.L. Identification and purification of classical Hodgkin cells from lymph nodes by flow cytometry and flow cytometric cell sorting. Am J Clin Pathol 2006;126(5):764–80. DOI: 10.1309/7371-XK6F-6P74-74XX

17. Grewal R.K., Chetty M., Abayomi E.A. et al. Use of flow cytometry in the phenotypic diagnosis of Hodgkin’s lymphoma. Cytometry B Clin Cytom 2019;96(2):116–27. DOI: 10.1002/cyto.b.21724

18. Wu D., Wood B.L., Fromm J.R. Flow cytometry for nonHodgkin and classical Hodgkin lymphoma. Methods Mol Biol 2013;971:27–47. DOI: 10.1007/978-1-62703-269-8_2

19. Abbasbeyli F.M., Fedenko A.A., Zeynalova P.A. et al. Clinical possibilities of flow cytometry in Hodgkin’s lymphoma. Onkogematologiya = Oncohematology 2023;18(3):70–7. (In Russ.). DOI: 10.17650/1818-8346-2023-18-3-70-77

20. Grivtsova L.Yu., Melnikova A.A., Mushkarina T.Yu. et al. Method for detecting Berezovsky–Reed–Sternberg cells in lymph nodes of patients with classical Hodgkin’s lymphoma by high-resolution 11-parameterflow cytometry. Patent RU 2 818 081 C2, 24.04.2024. Application No. 2023122175 dated 25.08.2023 (In Russ.).

21. Abbasbeyli F.M., Zeynalova P.A., Vernyuk M.A. et al. Bone marrow composition features and possibilities of tumor involvement diagnosing in patients with classic Hodgkin’s lymphoma. Onkogematologiya = Oncohematology 2023;18(3):84–91. (In Russ.). DOI: 10.17650/1818-8346-2023-18-3-84-91

22. Abbasbeyli F.M., Fedenko A.A., Zeynalova P.A. et al. Identification of Reed–Berezovsky–Sternberg cells in lymphatic nodes in classic Hodgkin’s lymphoma by flow cytometry: a clinical case series. Almanac of Clinical Medicine 2023;51(2):134–42. (In Russ.). DOI: 10.18786/2072-0505-2023-51-015