Preview

Russian Journal of Biotherapy

Advanced search

PPROACHES TO THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE IN B-CELL ACUTE LYMPHOBLASTIC LEUKEMIAS IN CONDITIONS OF TARGET THERAPY

https://doi.org/10.17650/1726-9784-2017-16-4-18-24

Abstract

Background. Flow cytometry (FC) algorithms of detection of minimal residual disease (MRD) are well standardized, and approximate to molecular biologic methods. However, besides informative leukemia-associated aberrant immunophenotype, which are selected taking into account a tumor phenotype at diagnostics stage, it is necessary to consider specificity of the provided taget therapy and its influence on a cell. Objective: to offer stable combinations of antigens to identify B-cell precursors in patients on therapy of blinatumomab. Materials and methods. Clinical observation of patient G. 4 years old with B-cell precursors acute lymphoblastic leukemia (ALL) (pre-pre-B immunosubtype), whom after 3 bloks of reinduction therapy, taking into account MRD-positive status, blinatumomab was appointed as a monotherapy. Tumor immunophenotype was characterized in details by FC protocol according to EuroFlow in debute and relapse of the disease. MRD monitoring was provided by 8-color FC taking into account personalized leukemia-associated aberrant immunophenotypes. Results. In patient with B-cell precursors ALL received blinatumomab, the strategy of MRD monitoring was changed. Due to the lack of CD19 expression, identification of B-cell precursors was based on expression of cyCD22 in combination with nuclear TdT and CD10. Conclusion. In case of blinatumomab’s appointment during B-cell precursors ALL therapy, it is necessary to change the strategy of B-cell precursors identification, due to the lack of CD19 expression. Detection of B-cell precursors should be provided by assessment of other pan-B lineage antigens. First of all, it is cyCD22 or cyCD79a in combination with nuclear TdT and CD10, within the limits of nucleated cells of the sample.

About the Authors

O. A. Beznos
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation


L. Yu. Grivtsova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation


A. V. Popa
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation


M. A. Shervashidze
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation


I. N. Serebryakova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation


N. N. Tupitsyn
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation


References

1. Borowitz M.J., Devidas M., Hunger S.P. et al. Clinical significance of minimal residual disease in children acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children’s Oncology Group study. Blood 2008; 111(12): 5477-85. DOI: 10.1182/blood-2008-01-132837. PMID: 18388178.

2. Dworzak M.N., Froschl G., Printz D. et al. Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. Blood 2002; 99(6): 1952-8. DOI: 10.1182/ blood.V99.6.1952. PMID: 11877265.

3. Безнос О.А., Гривцова Л.Ю., Попа А.В. и др. Определение минимальной остаточной болезни при В-линейных острых лимфобластных лейкозах с использованием подходов EuroFlow. Клиническая онкогематология 2017; 10(2): 158-68.

4. van Dongen J.J., van der Velden V.H., Bruggemann M., Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood 2015; 26(125): 3996-4009. DOI: 10.1182/blood-2015-03-580027. PMID: 25999452.

5. Litzow M.R. Antigen-based immunotherapy for the treatment of acute lymphoblastic leukemia: the emerging role of blinatumomab. Immunotargets Ther 2014; 3: 79-89. DOI: 10.2147/ITT.S37292. PMID: 27471701.

6. Hoffman L.M., Gore L. Blinatumomab, a bi-specific anti-CD19/CD3 BiTE® antibody for the treatment of acute lymphoblastic leukemia: perspectives and current pediatric applications. Front Oncol 2014; 4: 63. DOI: 10.3389/fonc.2014.00063. PMID: 24744989. Wolach O., Stone R.M. Blinatumomab for the treatment of Philadelphia chromosome-negative, precursor B-cell acute lymphoblastic leukemia. Clin Cancer Res 2015; 21(19): 4262-9. DOI: 10.1158/1078-0432.CCR-15-0125. PMID: 26283683.

7. Przepiorka D., Ko C.W., Deisseroth A. et al. FDA approval: Blinatumomab. Clin Cancer Res 2015; 21(18): 4035-9. DOI: 10.1158/1078-0432.CCR-15-0612. PMID: 26374073.

8. Gokburget N., Zugmaier G., Klinger M. et al. Long-term relapse-free survival in a phase 2 study of blinatumomab for the treatment of patients with minimal residual disease in B-lineage acute lymphoblastic leukemia. Haematologia 2017; 102(4): 132-5. DOI: 10.3324/haematol.2016.153957. PMID: 28082340.

9. Klinger M., Brandl C., Zugmaier G. et al. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood 2012; 119(26): 6226-33. DOI: 10.1182/blood-2012-01-400515. PMID: 22592608.

10. Topp M.S., Gökbuget N., Zugmaier G. et al. Long-term follow-up of hematologic relapse-free survival in a phase 2 study of blinatumomab in patients with MRD in B-lineage ALL. Blood 2012; 120(26): 5185-7. DOI: 10.1182/blood-2012-07-441030. PMID: 23024237.

11. Lee K.J., Chow V., Weissman A. et al. Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. Ther Clin Risk Manag 2016; 12: 1301-10. DOI: 10.2147/TCRM.S84261. PMID: 27601914.

12. Dworzak M.N., Fritsch G., Froschl G. et al. Four-color flow cytometric investigation of terminal deoxynucleotidyl transferase-positive lymphoid precursors in pediatric bone marrow: CD79a expression precedes CD19 in early B-cell ontogeny. Blood 1998; 92(9): 3203-9. PMID: 9787156.

13. Ruella M., Barrett D.M., Kenderian S.S. et al. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest 2016; 126(10): 3814-26. DOI: 10.1172/JCI87366. PMID: 27571406.

14. Veltroni M., De Zen L., Sanzari M.C. et al. Expression of CD58 in normal, regenerating and leukemic bone marrow B-cells: implications for the detection of minimal residual disease in acute lymphocytic leukemia. J Hematol 2003; 88(11): 1245-52. PMID: 14607753.

15. Romero-Ramirez H., Morales-Guadar-rama M.T., Pelayo R. et al. CD38 expression in early B-cell precursors contributes to extracellular signal-regulated kinasemediated apoptosis. Immunology 2014; 144(2): 271 -81. DOI: 10.1111/imm.12370. PMID: 25155483.

16. Гривцова Л.Ю., Попа А.В., Купрыши-на НА. и др. Оценка минимальной резидуальной болезни при острых лимфобластных лейкозах из В-линейных предшественников у детей методом трехцветной проточной цитометрии. Иммунология гемопоэза 2008; 5(2): 8-33.

17. Гривцова Л.Ю., Попа А.В., Серебрякова И.Н., Тупицын Н.Н. К дальнейшей стандартизации определения остаточных бластных клеток в костном мозге детей с В-линейными острыми лимфобластными лейкозами на 15-й день индукционной терапии. Иммунология гемопоэза 2011; 8(1): 35-54.

18. Гривцова Л.Ю., Тупицын Н.Н. Иммунологическая оценка гемодиллюции костного мозга при лабораторных исследованиях (на основании теста М. Локен). Медицинский алфавит 2015; 18(259): 67-70.


Review

For citations:


Beznos O.A., Grivtsova L.Yu., Popa A.V., Shervashidze M.A., Serebryakova I.N., Tupitsyn N.N. PPROACHES TO THE ASSESSMENT OF MINIMAL RESIDUAL DISEASE IN B-CELL ACUTE LYMPHOBLASTIC LEUKEMIAS IN CONDITIONS OF TARGET THERAPY. Russian Journal of Biotherapy. 2017;16(4):18-24. (In Russ.) https://doi.org/10.17650/1726-9784-2017-16-4-18-24

Views: 511


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1726-9784 (Print)
ISSN 1726-9792 (Online)