STUDY OF MINIMAL RESIDUAL DISEASE BY MULTICOLOR FLOW CYTOMETRY IN MULTIPLE MYELOMA AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

The frequency of achieving complete remission, as well as overall and disease-free survival, in multiple myeloma (MM) had increased due to introduction in MM treatment regimens of high-dose chemotherapy with following autologous hematopoietic stem cell transplantation (ASCT). However the number of relapses remains high, caused by persistence of residual tumor cells, i.e., the presence of minimal residual disease (MRD). One of the methods for MRD study is multicolor flow cytometry (MFC) where abnormal expression of surface antigens on myeloma plasma cells (PC) is determined. The aim of our study was to investigate the MRD by MFC before and after ASCT, the frequency of MRD-negative status achievement in complete remission (CR) patients at +100 days after ASCT and the frequency of abnormal expressed antigens on myeloma plasma cells. The study included40 MMpatients in CR at +100 days after ASCT and showed that the most common aberrations of PC were: abnormal absence of CD19 and/or CD27, decreased expression of CD38 and abnormal presence of CD56. The proportion of myeloma PCs from all bone marrow cells decreased significantly after ASCT: 20 % of patients acquired MRD-negative status, 10 % had a decrease in the number of abnormal PCs by one fold. Analysis of probability of immunochemical relapse showed that the worst prognosis was in patients with MRD-positive status before and after ASCT. During the MRD monitoring within 3-18 months, MRD-relapses were detected with the subsequent development of immunochemical relapse. The detection MRD in the dynamics is more informative than the study at only one step of therapy. It may help to select more adequate treatment for patient with multiple myeloma in each specific case. 

1. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные клинические рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология 2016,61(2):1–24. [Mendeleeva L.P., Votyakova O.M., Pokrovskaya O.S. et al. National clinical guidelines for the diagnosis and treatment of multiple myeloma. Gematologiya I transfuziologiya = Hematology and transfusiology, 2016,61(2):1–24 (In Russ.)]. DOI 10.18821/0234-5730-2016-61-1.

2. Rajkumar S., Dimopoulos M., Palumbo A. et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014,15(12):538–48. DOI: 10.1016/s1470-2045(14)70442-5. PMID: 25439696.

3. Покровская О.С., Менделеева Л.П., Урнова Е.С. и др. Мобилизация аутологичных гемопоэтических клеток с использованием высоких доз циклофосфана и Г-КСФ у больных множественной миеломой. Вестник гематологии 2009,5(2):33–4. [Pokrovskaya O.S., Mendeleeva L.P., Urnova E.A. et al. Autologous hematopoietic cells mobilization using high doses of cyclophosphamide and G-CSF in patients with multiple myeloma. Vestnik gematologii = Bulletin of Hematology, 2009,5(2):33–4 (In Russ.)].

4. Paiva B., Vidriales M., Cervero J. et al. Multiparameter flow cytometric remission is the most relevant prognostic factor for multiple myeloma patients who undergo autologous stem cell transplantation. Blood 2008,112(10):4017–23. DOI: 10.1182/blood-2008-05-159624. PMID: 18669875.

5. Paiva B., Almeida J., Pérez-Andrés M. et al. Utility of flow cytometry immunophenotyping in multiple myeloma and other clonal plasma cell-related disorders. Cytometry B Clin Cytom 2010,78(4):239–52. DOI:10.1002/cyto.b.20512. PMID: 20155853.

6. Rawstron A., Orfao A., Beksac M. et al. Report of the European Myeloma Network on multiparametric flow cytometry in multiple myeloma and related disorders. Haematologica 2008,93(3):431–8. DOI:10.3324/haematol.11080. PMID: 18268286

7. Stetler-Stevenson M., Paiva B., Stoolman L. et al. Consensus guidelines for myeloma minimal residual disease sample staining and data acquisition. Cytometry B Clin Cytom. 2015,90(1):26–30. DOI:10.1002/cyto.b.21249. PMID: 25907102

8. Rajkumar S.V. Multiple myeloma: 2016 update on diagnosis, risk-stratification, and management. Am J Hematol 2016,91(7):719–34. DOI: 10.1002/ajh.24402. PMID: 27291302

9. Flores-Montero J., de Tute R., Paiva B. et al. Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma. Cytometry B Clin Cytom 2015,90(1):61–72. DOI:10.1002/cyto.b.21265. PMID: 26100534

10. Kristinsson S.Y., Landgren O., Dickman P.W. et al. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol 2007,25(15):1993–9. DOI: 10.1200/JCO.2006.09.0100. PMID: 17420512.

11. Kumar S. K., Rajkumar S.V., Dispenzieri A. et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008,111(5):2516–20. DOI: 10.1182/blood-2007-10-116129. PMID: 17975015.

12. Rawstron A., Child J., de Tute R. et al. Minimal Residual Disease Assessed by Multiparameter Flow Cytometry in Multiple Myeloma: Impact on Outcome in the Medical Research Council Myeloma IX Study. J Clin Oncol 2013,31(20):2540–7. DOI:10.1200/jco.2012.46.2119. PMID: 23733781.