ISSN 2415-3060 (print), ISSN 2522-4972 (online)
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УЖМБС 2021, 6(1): 56–64
Clinical Medicine

Immunophenotypic Profile of Blast Cells as a Marker for Diagnosis of Relapsed Children Acute Lymphoblastic Leukemia

Vynnytska O. A., Dorosh O. I., Dubey L. Ya., Dubey N. V.

Immunophenotyping of leukemia cells was studied in this work; minimal residual disease was monitored among children with acute lymphoblastic leukemia under conditions of relapse and complete remission after the application of ALLIC-BFM 2009 cytostatic therapy. The study showed that after application of ALLIC-BFM 2009 therapy, 88% of children had complete remission, and 12% had relapses. Among patients with relapses, the number of blast cells in the bone marrow was at a high level (more than 6%). Monitoring of patients during therapy established an increase in the minimal residual disease level of more than 1% after treatment in patients with recurrent disease. Immunophenotyping of blast cells among patients with relapse showed the expression of linear independent antigens HLA (93%), Auti-TdT (91%), CD10 (78%), CD38 (91%) and CD34 (57%) and B-linear antigens: CD19, CD22, CD58, CD79a, the highest expression was found for the CD19 antigen. A low level of expression of CD45 (28%) was recorded with relapses of acute lymphoblastic leukemia and high (89%) level was with complete remission of the disease. We did not detect expression of antigens characteristic of T-cell acute lymphoblastic leukemia in bone marrow of patients with acute lymphoblastic leukemia, both with relapses and with remission. At the same time, the expression of myeloid antigens (CD33 and CD13) was noted among acute lymphoblastic leukemia patients. Among patients, the incidence of acute lymphoblastic leukemia was the most pronounced in children aged from 3 to 6 years – 37 patients (35.2%) and aged from 6 to 9 years – 26 (24.8%) patients. The highest accidence was found among patients with chromosomal translocation TEL / AML – 22 (21%) patients with a median age 5 years. In second place, the frequency of mutations is the translocation of E2A / PBX1. BCR / ABL translocation was less common. It was noted in 1.9% of patients, but the expression of this gene indicated a bad course of the disease, as patients after cytostatic therapy under the ALLIC BFM 2009 program had a recurrence. Recurrence was also observed in patients with TEL/AML chromosomal translocation. Determination of minimal residual disease showed its increased level in patients with chromosomal aberrations BCR / ABL and TEL/AML throughout the treatment phase. In addition, patients in these groups were diagnosed with initial leukocytosis followed by leukopenia after a course of chemotherapy. Patients of all groups showed a decrease in hemoglobin. The biggest changes in clinical and laboratory parameters were found between patients with chromosomal translocations BCR/ABL and TEL/AML, as evidenced by the development of relapses in patients of these groups. The low level of association between karyotype disorders, with the formation of AF4/MLL and E2A/PBX1, and clinical and laboratory parameters in patients with acute lymphoblastic leukemia may indicate that the isolated clonal disorders are independent prognostic factors for the course of the disease

Keywords: immunophenotype, blast cells, antigens, minimal residual disease, childhood acute lymphoblastic leukemia

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  1. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med. 2015 Oct 15; 373(16): 1541-52.
  2. Kato M, Manabe A. Treatment and biology of pediatric acute lymphoblastic leukemia. Pediatr Int. 2017 Nov 16; 60(1): 4-12.
  3. Iacobucci I, Mullighan CG. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol. 2017 Mar 20; 35(9): 975-983. doi: 10.1200/JCO.2016.70.7836
  4. Loghavi S, Kutok JL, Jorgensen JL. B-acute lymphoblastic leukemia/lymphoblastic lymphoma. Am J Clin Pathol. 2015 Jan 05; 144(3): 393-410.
  5. Chiu H, Trisal P, Bjorklund C, Carrancio S, Toraño EG, Guarinos C, et al. Combination lenalidomide-rituximab immunotherapy activates anti-tumour immunity and induces tumour cell death by complementary mechanisms of action in follicular lymphoma. Br J Haematol. 2019 Feb 14; 185(2): 240-253.
  6. Głowala-Kosińska M, Chwieduk A, Nieckula J, Saduś-Wojciechowska M, Grosicki S, Rusin A, et al. Association of circulating regulatory T cell number with the incidence and prognosis of diffuse large B-cell lymphoma. Eur J Haematol. 2013 May 17; 91(2): 122-8.
  7. Leahy AB, Elgarten CW, Grupp SA, Maude SL, Teachey DT. Tisagenlecleucel for the treatment of B-cell acute lymphoblastic leukemia. Expert Rev Anticancer Ther. 2018 Sept 05; 18(10): 959-971.
  8. Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 05; 131(14): 1522-1531.
  9. Theunissen P, Mejstrikova E, Sedek L, van der Sluijs-Gelling AJ, Gaipa G, Bartels M, et al. Standardized flow cytometry for highly sensitive MRD measurements in B-cell acute lymphoblastic leukemia. Blood. 2017 Jan 19; 129(3): 347-357.
  10. Glier H, Novakova M, Te Marvelde J, Bijkerk A, Morf D, Thurner D, et al. Comments on EuroFlow standard operating procedures for instrument setup and compensation for BD FACS Canto II, Navios and BD FACS Lyric instruments. J Immunol Methods. 2019 Dec; 475: 112680.
  11. Raetz EA, Teachey DT. T-cell acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2016 Dec 02; 2016(1): 580-588.
  12. Kang ZJ, Liu YF, Xu LZ, Long ZJ, Huang D, Yang Y, et al. The Philadelphia chromosome in leukemogenesis. Chin J Cancer. 2016 May 27; 35: 48.
  13. Stein AS, Kantarjian H, Gökbuget N, Bargou R, Litzow MR, Rambaldi A, et al. Blinatumomab for acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019 Apr 16; 25(8): 1498-1504.
  14. Kater AP, Seymour JF, Hillmen P, Eichhorst B, Langerak AW, Owen C, et al. Fixed duration of venetoclax-rituximab in relapsed/refractory chronic lymphocytic leukemia eradicates minimal residual disease and prolongs survival: post-treatment follow-up of the MURANO phase III study. J Clin Oncol. 2019 Feb 01; 37(4): 269-277.
  15. Czyz A, Nagler A. The role of measurable residual disease (MRD) in hematopoietic stem cell transplantation for hematological malignancies focusing on acute leukemia. Int J Mol Sci. 2019 Oct 28; 20(21): 5362.
  16. Pillai V, Muralidharan K, Meng W, Bagashev A, Oldridge DA, Rosenthal J, et al. CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy. Blood Adv. 2019 Nov 18; 3(22): 3539-3549.
  17. Grivtsova LY. Evaluation of minimal residual disease in b-lineage acute lymphoblastic leukemia using euroflow approaches. Clinical oncohematology. 2017 Jan 29; 10(2): 158-168.
  18. Rieger MA, Schroeder T. Hematopoiesis. Cold Spring Harb Perspect Biol. 2012; 4(12): a008250.
  19. Zevedo Portilho N, Pelajo-Machado M. Mechanism of hematopoiesis and vasculogenesis in mouse placenta. Placenta. 2018 Sept; 69: 140-145.
  20. Ginhoux F, Guilliams M. Tissue-resident macrophage ontogeny and homeostasis. Immunity. 2016 Feb 24; 44(3): 439-449.
  21. Ying Z, Huang XF, Xiang X, Liu Y, Kang X, Song Y, et al. A safe and potent anti-CD19 CAR T cell therapy. Nat Med. 2019 Apr 22; 25(6): 947-953.
  22. Katz BZ, Herishanu Y. Therapeutic targeting of CD19 in hematological malignancies: past, present, future and beyond. Leuk Lymphoma. 2013 Sept 03; 55(5): 999-1006.
  23. Gorczyca W, Sun ZY, Cronin W, Li X, Mau S, Tugulea S. Immunophenotypic pattern of myeloid populations by flow cytometry analysis. Methods Cell Biol. 2011; 103: 221-66.