Minimal Residual Disease and Acute Leukemia

*Normal and Malignant B-Cell*

2011;**12**(11):1013-1022

1993;**328**(14):1002-1006

2011;**378**(9806):1858-1867

open-label randomised study of the MabThera International Trial (MInT) Group. The Lancet Oncology. inhibitor. Journal of Hematology & Oncology. 2016;**9**:21. DOI: 10.1186/

[37] Maffei R, Fiorcari S, Martinelli S, Potenza L, Luppi M, Marasca R. Targeting neoplastic B cells and harnessing microenvironment: The "double face" of ibrutinib and idelalisib. Journal of Hematology & Oncology. 2015;**8**:60. DOI: 10.1186/

[38] Salles G, Gopal AK, Minnema MC, Wakamiya K, Feng H, Schecter JM, et al. Phase 2 study of daratumumab in relapsed/refractory mantle-cell lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma. Clinical Lymphoma, Myeloma & Leukemia. 2019;pii: S2152-2650 (18):31284-31289. DOI: 10.1016/j. clml.2018.12.013 [Epub ahead of print]

s13045-016-0250-9

s13045-015-0157-x

[31] Fletcher CD, Kahl BS. Central nervous system involvement in diffuse large B-cell lymphoma: An analysis of risks and prevention strategies in the post-rituximab era. Leukemia & Lymphoma. 2014;**55**(10):2228-2240

[32] Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, et al. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. The New England Journal of Medicine.

[33] Recher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O, et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): An openlabel randomised phase 3 trial. Lancet.

[34] He Y, Li J, Ding N, Wang X, Deng L, Xie Y, et al. Combination of enzastaurin and ibrutinib synergistically induces anti-tumor effects in diffuse large B cell lymphoma. Journal of Experimental & Clinical Cancer Research. 2019;**38**(1):86.

DOI: 10.1186/s13046-019-1076-4

et al. Clinical significance of metabolism-related biomarkers in non-Hodgkin lymphoma—MCT1 as potential target in diffuse large B cell lymphoma. Cellular Oncology (Dordrecht). 2019. DOI: 10.1007/ s13402-019-00426-2 [Epub ahead of

[36] Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): A selective second-generation BTK

[35] Afonso J, Pinto T, Simões-Sousa S, Schmitt F, Longatto-Filho A, Pinheiro C,

**104**

print]

**107**

**Chapter 6**

**Abstract**

**1. Introduction**

assessment.

B-Cell Precursors:

Immunophenotypic Features in

Disease in Acute Leukemia

*Olga Chernysheva, Lyudmila Yuryevna Grivtsova,* 

associated immunophenotype in monitoring of the MRD.

**Keywords:** bone marrow, B-cell precursors, acute leukemia,

*Alexander Popa and Nikolay Nikolayevich Tupitsyn*

the Detection of Minimal Residual

Minimal residual disease (MRD) as a tool to monitor response to therapy is both a criterion for detailed risk stratification and an independent prognostic factor in childhood acute lymphoblastic leukemia (ALL). Immunological assays particularly flow cytometry (FC) are priority methods in MRD monitoring. Multicolor flow cytometry makes it possible to most fully characterize the immunophenotype of tumor B lymphoblasts and reveal leukemia-associated immunophenotypes not only according to the CD58 and CD38 antigens but also as an additional criterion of aberrancy. This allows you to identify and select individual criteria for further monitoring of minimal residual disease for each patient with ALL. The aim of this chapter is to compare immunophenotyping features of normal B-cell precursors and B-lymphoblasts in acute leukemia and to show possibilities of use of a leukemia-

leukemia-associated immunophenotype, flow cytometry, minimal residual disease

Control of response to chemotherapy is an intrinsic part of current treatment protocols [1–5]. Assessment of response in key points of chemotherapy programs helps both to stratify patients by risk groups more accurately and to avoid serious chronic side effects and patient overtreatment [6–12]. In case of acute leukemia, the number of tumor blasts undetectable in bone marrow (BM) morphologically at different therapy stages or minimal residual disease (MRD) is a criterion for such

In adult patients, problems of most significant points of immunological detection and the role of MRD levels are a matter of discussion [2]. The MRD significance is demonstrated in full in pediatric oncology. The MRD is of importance both in prognosis of acute lymphoblastic leukemia (ALL) and in prediction of recurrence [13]. Key points for MRD assessment are determined as well as their clinical signifi-

cance and MRD levels that help in detailed risk stratification of patients [1].
