Acute Myeloid Leukemias After the Treatment of Classical Hodgkin’s Lymphoma: A Literature Review

AA Danilenko, SV Shakhtarina, NA Falaleeva

AF Tsyb Medical Radiological Research Centre, branch of the NMRC of Radiology, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036

For correspondence: Anatolii Aleksandrovich Danilenko, MD, PhD, 4 Koroleva ul., Obninsk, Kaluga Region, Russian Federation, 249036; Tel.: +7(909)250-18-10; e-mail: danilenkoanatol@mail.ru

For citation: Danilenko AA, Shakhtarina SV, Falaleeva NA. Acute Myeloid Leukemias After the Treatment of Classical Hodgkin’s Lymphoma: A Literature Review. Clinical oncohematology. 2022;15(4):414–23. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-414-423


ABSTRACT

Second malignant tumors occurring in classical Hodgkin’s lymphoma (cHL) patients after treatment include mainly solid neoplasms and far more rarely acute myeloid leukemias (AML). At the same time, a relative risk of developing secondary AML substantially exceeds the risks of second (solid) tumors, and the efficacy of secondary AML treatment is considerably lower compared to the outcomes of primary AML treatment. All that implies the importance and relevance of this issue. The present literature review discusses the epidemiology of developing secondary AMLs in patents after cHL treatment. In addition to that, it focuses on modern drugs and technologies for effective treatment of secondary AMLs.

Keywords: classical Hodgkin’s lymphoma, secondary acute myeloid leukemias.

Received: April 15, 2022

Accepted: August 28, 2022

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Статистика Plumx английский

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Cytogenetic Characterization of Complex Karyotypes by Multicolor FISH in Myelodysplastic Syndromes and Associated Acute Myeloid Leukemias

MV Latypova, NN Mamaev, TYu Gracheva, TL Gindina

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

For correspondence: Prof. Nikolai Nikolaevich Mamaev, MD, PhD, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022; e-mail: nikmamaev524@gmail.com

For citation: Latypova MV, Mamaev NN, Gracheva TYu, Gindina TL. Cytogenetic Characterization of Complex Karyotypes by Multicolor FISH in Myelodysplastic Syndromes and Associated Acute Myeloid Leukemias. Clinical oncohematology. 2022;15(4):396–413. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-396-413


ABSTRACT

Complex karyotypes (CK) were thoroughly analyzed by using the data of multicolor FISH in 27 patients with myelodysplastic syndromes (MDS) and MDS-associated acute myeloid leukemias (AMLm). Despite a vast variety of identified genetic impairments, chromosomes 5, 8, and 7 appeared to be most frequently (79 %, 76 %, and 73 %, respectively) involved in rearrangements, a fact also documented in literature. In view of this, two independent cytogenetic subgroups with chromosome 5/7 and 5/7/8 rearrangements were formed. Chromosomes 5 and 7 predominantly showed unbalanced karyotype, and chromosome 8 was characterized by its combinations with trisomies. The study also revealed that complex markers, more often than the other ones, contain chromosome 7 material, which has not so far been adequately explained. At the same time, the accumulation of chromosome 8 material in CK was associated with a more favorable course of underlying disease. On the other hand, detailed structural analysis of some supercomplex CK markers affords grounds for the assertion that chromothripsis notably participates in their formation. The overall survival of MDS and AMLm patients in artificially formed joint subgroups with combinations of involved chromosomes 5/7 and 5/7/8 was significantly lower than in AMLm (= 0.035).

Keywords: MDS, MDS-associated AML, complex karyotypes and markers, chromothripsis, multicolor FISH, chromosome 5, 7, and 8 rearrangements, clinical value.

Received: June 4, 2022

Accepted: September 7, 2022

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Статистика Plumx английский

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The Importance of Complementary Immunological Markers in the Diagnosis of Minimal Residual Disease in Multiple Myeloma

EE Tolstykh1, OS Chuvadar2, AA Semenova1, NA Kupryshina1, OP Kolbatskaya1, YuI Klyuchagina1, OA Kolomeitsev1, GS Tumyan1, NN Tupitsyn1

1 NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 Center of Clinical Oncology and Hematology, 4a Semashko ul., Simferopol, Republic of Crimea, Russian Federation, 295026

For correspondence: Prof. Nikolai Nikolaevich Tupitsyn, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(925)537-15-82; e-mail: nntca@yahoo.com

For citation: Tolstykh EE, Chuvadar OS, Semenova AA, et al. The Importance of Complementary Immunological Markers in the Diagnosis of Minimal Residual Disease in Multiple Myeloma. Clinical oncohematology. 2022;15(4):388–95. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-388-395


ABSTRACT

Background. The population of non-tumor plasma cells in healthy subjects’ bone marrow is known to be fairly heterogeneous. Among them, there may be a small number of CD19–, CD56+, CD45– plasma cells which differ from the main bulk of the normal plasmacytic cells by the lack of CD19 and CD45 expression and the presence of CD56 expression. It is the fact which makes the monitoring of minimal residual disease (MRD) especially challenging in multiple myeloma (MM) since normal and aberrant plasma cells should be compared. For this reason, a study of such complementary diagnostic markers as CD27, CD28, CD117, and CD81 is extremely important.

Aim. To analyze the role of complementary diagnostic markers (CD27, CD28, CD117, and CD81) of MRD in MM patients at different disease stages.

Materials & Methods. The present study enrolled 62 MM patients aged 31–76 years (median 58 years); 25 women and 37 men. The analysis focused on morphological and immunophenotypic properties of bone marrow plasma cells. MRD was detected by 8-color flow cytometry with the use of FACSCanto II Flow Cytometer (USA) based on EuroFlow standards.

Results. At the stage of primary diagnosis of MM, the immunophenotype of plasma cells was analyzed in all 62 patients using two 8-color panels recommended by the EuroFlow Consortium (2012). In accordance with primary immunophenotyping data, MRD was evaluated on the basis of not only the main diagnostic markers of plasma cells (CD38, CD138, CD45, CD56, and CD19), but also the complementary ones, such as CD27, CD28, CD117, and CD81. The study was basically conducted after induction therapy and upon remission. With cut-off > 0.01 % of aberrant plasma cells, the MRD incidence was the following: 91.0 % with CD27, 90.6 % with CD28, 87.0 % with CD117, and 96.7 % with CD81 markers. Respectively, no MRD was detected in 9.0 % with CD27, 9.4 % with CD28, 13.0 % with CD117, and 3.3 % with CD81 markers.

Conclusion. Using the set of complementary markers including CD27, CD28, CD117, and CD81 allows to establish a more accurate MRD status in MM, i.e. either negative or positive one, taking into account the expression of basic antigens CD38, CD138, CD45, CD56, and CD19.

Keywords: multiple myeloma, minimal residual disease, plasma cells, bone marrow, multicolor flow cytometry.

Received: March 2, 2022

Accepted: August 30, 2022

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REFERENCES

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The Prognostic Value of Immunophenotypic Characteristics of Plasma Cells in Newly Diagnosed Multiple Myeloma Patients Treated with First-Generation Proteasome Inhibitor Bortezomib

GN Salogub1, EB Rusanova2, MV Gorchakova2, EA Belyakova3

1 VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341

2 IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo ul., Saint Petersburg, Russian Federation, 197022

3 II Mechnikov North-Western State Medical University, 41 Kirochnaya ul., Saint Petersburg, Russian Federation, 191015

For correspondence: Galina Nikolaevna Salogub, MD, PhD, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341; e-mail: salogub@bk.ru

For citation: Salogub GN, Rusanova EB, Gorchakova MV, Belyakova EA. The Prognostic Value of Immunophenotypic Characteristics of Plasma Cells in Newly Diagnosed Multiple Myeloma Patients Treated with First-Generation Proteasome Inhibitor Bortezomib. Clinical oncohematology. 2022;15(4):377–87. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-377-387


ABSTRACT

Aim. To assess the number of plasma cells (PC) in the bone marrow and their immunophenotype using flow cytometry (FC) and light microscopy. To analyze clinical and prognostic value of the data obtained in newly diagnosed multiple myeloma (MM) patients treated with first-generation proteasome inhibitor bortezomib.

Materials & Methods. The study enrolled 153 newly diagnosed MM patients treated and followed-up at the IP Pavlov First Saint Petersburg State Medical University in the period from 2007 to 2017. The median age of patients was 69 years. In 115 patients, the regimens based on first-generation proteasome inhibitor bortezomib were used as induction therapy. To determine the immunophenotypic profile of PC, the CD19, CD20, CD27, CD38, CD45, CD56, CD138, and CD117 monoclonal antibodies were used. PC immunophenotyping in the bone marrow was performed by FC using Cytomics FC500 (Beckman Coulter, USA).

Results. Patients with different phenotypes did not show any considerable differences in monocloncal production of certain classes and types of immunoglobulin heavy and/or light chains. In case of immunophenotypic profile of CD20+CD27– myeloma cells, the secretion of the monoclonal κ-chain predominated over that of λ-chain. By and large, the secretion of light chains was observed more often in ММ CD20+ and more seldom in ММ CD56+. In case of CD56 expression, IgAλ secretion was more often reported; IgAκ secretion was more common in case of CD117 expression. Worst survival scores were shown by patients with PC immunophenotype CD27–CD56–. At the primary MM diagnosis, the advanced stages of the disease, according to the ISS, were more commonly characterized by phenotype CD45–CD27–CD56+.

Conclusion. The flow cytometry characteristics of PC immunophenotype can be applied to evaluate the prognosis of MM and to optimize the therapy.

Keywords: multiple myeloma, flow cytometry, bortezomib, immunophenotypic profile, plasma cells, overall survival, progression-free survival.

Received: May 22, 2022

Accepted: August 28, 2022

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Multiple Myeloma: Nuances of Minimal Residual Disease Diagnosis and Monitoring with the Use of Multicolor Flow Cytometry

IV Galtseva, KA Nikiforova, YuO Davydova, NM Kapranov, MV Solov’ev, EN Parovichnikova, LP Mendeleeva

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Kseniya Aleksandrovna Nikiforova, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-62-21; e-mail: nikiforovaksenya@gmail.com

For citation: Galtseva IV, Nikiforova KA, Davydova YuO, et al. Multiple Myeloma: Nuances of Minimal Residual Disease Diagnosis and Monitoring with the Use of Multicolor Flow Cytometry. Clinical oncohematology. 2022;15(4):365–76. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-365-376


ABSTRACT

The assessment of minimal residual disease (MRD) by multicolor flow cytometry (MFC) is a rapidly growing area of laboratory studies. In recent years, it has become particularly valuable for hematologists. Although the MFC analysis of plasma cells in multiple myeloma patients is sufficiently standardized, there are differences in methods of sample preparation, monoclonal antibody combinations being used as well as in cytometric data evaluation. The present paper summarizes the key international and domestic data on the MFC analysis of plasma cells and documents the authors’ own experience with MFC analysis in multiple myeloma over the last few years.

Keywords: minimal residual disease, multiple myeloma, multicolor flow cytometry, gating, immunophenotyping.

Received: May 24, 2022

Accepted: August 10, 2022

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Статистика Plumx английский

REFERENCES

  1. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538–e548. doi: 10.1016/S1470-2045(14)70442-5.
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Plasmablastic Lymphoma with Primary Impairment of Bone Marrow in a HIV-Negative Patient: A Literature Review and a Case Report

MV Firsova, MV Solov’ev, AM Kovrigina, LP Mendeleeva

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Maiya Valerevna Firsova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: firs-maia@yandex.ru

For citation: Firsova MV, Solov’ev MV, Kovrigina AM, Mendeleeva LP. Plasmablastic Lymphoma with Primary Impairment of Bone Marrow in a HIV-Negative Patient: A Literature Review and a Case Report. Clinical oncohematology. 2022;15(4):356–64. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-356-364


ABSTRACT

Background. Plasmablastic lymphoma (PBL) is a rare variant of large B-cell lymphoma. This disease is usually associated with HIV infection and is predominantly identified in male patients. Tumor lesion is typically localized in oral cavity. PBL is characterized by aggressivity and low rate of long-term survival.

Aim. To report a clinical case of a rare localization of PBL with primary impairment of bone marrow in a 19-year-old HIV-negative patient.

Materials & Methods. The diagnosis of the disease turned out to be challenging and was based on the results of a multi-step complex immunohistochemical analysis of a bone marrow core biopsy sample.

Results. Intensive block-based mNHL-BFM-90 polychemotherapy combined with bortezomib and daratumumab resulted in remission which allowed to perform consecutive autologous and then allogeneic hematopoietic stem cell transplantations. For the lack of immune control of allogeneic transplant over the tumor the conducted therapy was disappointingly unsuccessful. In other words, graft-versus-tumor effect could not be achieved. The patient died in 11 months after diagnosis because of tumor progression. A post-mortem report is required.

Conclusion. New approaches are definitely called for in order to explore methods of treating this complex disease. A study of mechanisms underlying PBL pathogenesis can contribute to better understanding of tumor biology and personalized choice of chemotherapy.

Keywords: plasmablastic lymphoma, CD38, bortezomib, daratumumab, auto-HSCT, allo-HSCT, bone marrow.

Received: May 4, 2022

Accepted: August 30, 2022

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Статистика Plumx английский

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Experience with the Use of B-RAF Inhibitor Vemurafenib in the Treatment of Hairy Cell Leukemia

LS Al-Radi, SYu Smirnova, TN Moiseeva, IS Piskunova, LV Plastinina, DV Novikova, EG Gemdzhian, GM Galstyan

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Svetlana Yurevna Smirnova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(926)879-65-94; e-mail: smirnova-s-ju@yandex.ru

For citation: Al-Radi LS, Smirnova SYu, Moiseeva TN, et al. Experience with the Use of B-RAF Inhibitor Vemurafenib in the Treatment of Hairy Cell Leukemia. Clinical oncohematology. 2022;15(4):349–55. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-349-355


ABSTRACT

Background. The standard and effective treatment of hairy cell leukemia (HCL) involves purine analogs, interferon-α (IFN-α) administration, and splenectomy. However, primary resistant HCL and early relapses (within 2–3 years after achieving remission) remain clinical challenges. Due to myelotoxicity of cladribine and slow effect of IFN-α, these drugs can be administered neither in deep neutropenia/agranulocytosis patients (especially in case of infectious complications) nor in patients with IFN-α allergy/intolerance.

Aim. To report clinical experience with vemurafenib, a B-RAF inhibitor, in HCL with BRAFV600E mutation in treatment-resistant patients with contraindications to standard therapy.

Materials & Methods. The study enrolled 39 HCL patients aged 24–78 years (median 55 years), 13 women and 26 men. HCL was diagnosed in accordance with the WHO 2017 criteria. Vemurafenib 240 mg was administered once or twice a day within 3 months. Three groups of patients were analyzed: those with early relapses and resistant HCL (n = 7), those with deep neutropenia/agranulocytosis (with and without infectious complications, n = 29), and those with IFN-α intolerance (n = 3).

Results. In 6 (86 %) out of 7 patients from group 1 (with early relapses and resistant HCL) a complete course of treatment was carried out, which included vemurafenib with subsequent standard cladribine chemotherapy and further consolidation with rituximab. Complete remission was achieved in 5 (71 %) patients, and partial remission was achieved in 1 (14 %) patient. The 7th patient was a non-responder. In 28 (97 %) out of 29 patients from group 2 with deep neutropenia/agranulocytosis, hematologic recovery was reported which allowed for further basic treatment with cladribine. In 1 patient vemurafenib appeared to be ineffective. In 3 patients from group 3 with IFN-α intolerance, vemurafenib administration was used as a stage of treatment preceding cladribine therapy. Cladribine treatment resulted in complete remission in 2 (67 %) patients and partial remission in 1 (33 %) patient.

Conclusion. In HCL with BRAFV600E mutation, low-dose vemurafenib can be effective in patients with relapsed/refractory disease as well as deep neutropenia with life-threatening infectious complications. In addition to that, vemurafenib administration can be used in cases of IFN-α intolerance as a stage of treatment of HCL with BRAFV600E mutation which precedes the basic cladribine therapy.

Keywords: hairy cell leukemia, B-RAF inhibitor, vemurafenib, relapsed/refractory disease, agranulocytosis, infectious complications.

Received: April 25, 2022

Accepted: September 2, 2022

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Статистика Plumx английский

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Production of CD87 Antigen-Specific CAR-T Lymphocytes and Assessment of Their In Vitro Functional Activity

MV Neklesova, SV Smirnov, AA Shatilova, KA Levchuk, AE Ershova, SA Silonov

Center for Personalized Medicine, VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341

For correspondence: Sergei Vladimirovich Smirnov, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341; Tel.: +7(964)612-57-14; e-mail: sergeiismirnoff@gmail.com

For citation: Neklesova MV, Smirnov SV, Shatilova AA, et al. Production of CD87 Antigen-Specific CAR-T Lymphocytes and Assessment of Their In Vitro Functional Activity. Clinical oncohematology. 2022;15(4):340–8. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-340-348


ABSTRACT

Aim. To generate anti-CD87 CAR-T lymphocytes and to assess their in vitro functional activity.

Materials & Methods. Т-lymphocytes isolated from healthy donor peripheral blood were transduced with the anti-CD87-CAR, T2A, and FusionRed gene coding lentiviral vector. Transduction efficacy assessed by reporter protein FusionRed signal, subpopulation structure, and functional status of CAR-T lymphocytes were determined by flow cytometry. Interferon-γ (IFN-γ) expression by CAR-T lymphocytes was analyzed using immunoassay. Cytotoxic activity of CAR-T lymphocytes was evaluated during their co-cultivation with HeLa target cells by means of xCELLigence real-time assay.

Results. The efficacy of T-lymphocyte transduction was 8.4 %. The obtained CAR-T cells contained the markers of both CD27 and/or CD28 activation (92.91 % cases) and PD1 exhaustion (20.66 % cases). The population of CAR-T lymphocytes showed 98.51 % central memory T-cell phenotype and CD4/CD8 ratio of 1:7. IFN-γ concentration in the medium after co-cultivation of CAR-T lymphocytes with target cells appeared to be significantly higher than in control samples. The study demonstrates that generated CAR-T lymphocytes manifest specific cytotoxicity towards target cells with both unmodified expression and overexpression of CD87 antigen in HeLa cell lines. Cytotoxicity proved to be more pronounced with respect to the cell line with CD87 antigen overexpression.

Conclusion. Despite overexpression of PD1 exhaustion marker, CAR-T lymphocytes showed specific IFN-γ secretion and pronounced cytotoxic activity in interaction with CD87 antigen on target cell membranes. Therefore, anti-CD87 CAR-T lymphocytes can be applied in the treatment of hematologic as well as solid tumors. Since the observed difference in cytotoxicity does not linearly correlate with CD87 antigen density on the surface of attacked cells, the in vivo administration of a CAR-T cell drug should be designed to prevent cytotoxic risk for CD87-expressing healthy cells.

Keywords: CD87, uPAR, CAR-T lymphocytes, acute myeloid leukemias.

Received: June 27, 2022

Accepted: September 10, 2022

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Experimental Study of the In Vitro and In Vivo Functional Activity of NKG2D Chimeric Antigen Receptor

KA Levchuk1, SA Osipova1, AV Onopchenko1, ML Vasyutina1, ER Bulatov2, AKh Valiullina2, ON Demidov1,3,4, AV Petukhov1

1 VA Almazov National Medical Research Center, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341

2 Kazan (Privolzhsky) Federal University, 18 Kremlevskaya ul., Kazan, Russian Federation, 420008

3 Institute of Cytology, 4 Tikhoretskii pr-t, Saint Petersburg, Russian Federation, 194064

4 Sirius University of Science and Technology, 1 Olimpiiskii pr-t, Sochi, Russian Federation, 354340

For correspondence: Kseniya Aleksandrovna Levchuk, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341; e-mail: levchuk_ka@almazovcentre.ru

For citation: Levchuk KA, Osipova SA, Onopchenko AV, et al. Experimental Study of the In Vitro and In Vivo Functional Activity of NKG2D Chimeric Antigen Receptor. Clinical oncohematology. 2022;15(4):327–39. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-327-339


ABSTRACT

Aim. To study antitumor cytotoxic effect of CAR-T NKG2D and CAR-T anti-CD19 in vitro and in vivo in order to compare antitumor activity of chimeric antigen receptors (CAR) with different structural and functional properties.

Materials & Methods. CAR constructions were produced by molecular cloning. CAR-T cell populations were obtained by transduction of healthy donor T-lymphocytes with recombinant lentiviral particles coding CAR NKG2D or CD19 target antigen CAR sequences. CAR-T cell proportion was assessed by FusionRed fluorescence and EGFR membrane receptor imaging. Specific in vitro cytotoxic activity of CAR-T effector cells was analyzed by Real-Time Cytotoxicity Assay (RTCA) during co-cultivation with HeLa_CD19 target cell line using xCELLigence. Interferon-γ (IFN-γ) synthesis in vitro and in vivo along with the degree of cytotoxic effect were analyzed by immunoassay of culture medium of co-cultivated effector cells and target cells as well as isolated auto-plasma from the peripheral blood of mice. To assess the in vivo functional activity, CAR-T cell populations were infused into immunodeficient NSG-SGM3 mice (10 000 000 cells/mouse) 12 days after HeLa_CD19 cell injection and confirmation of engraftment and tumor growth. Upon euthanasia, tumors were removed and fixed in paraffin to prepare histological sections. CAR-T cell tumor infiltration was assessed by CD3 antigen immunohistochemical staining.

Results. The highest ligand (molecules MICA, ULBP1/2/3/4/5/6) expression levels were detected in HeLa cell line. The obtained NKG2D CAR-T cells showed a considerable cytotoxic activity against HeLa_CD19 target line (cell index [CI] = 1.27), which was, however, twice as low as that of CAR-T anti-CD19 (CI = 0.60) (= 0.0038). IFN-γ level during co-cultivation of CAR-T anti-CD19 with HeLa_CD19 at the ratio of Е/Т = 1:1 was 64,852 pcg/mL, which was 3.5 times higher than IFN-γ level during co-cultivation of CAR-T NKG2D with HeLa_CD19 (18,635 pcg/mL) (= 0.0360). The degree of tumor infiltration by CAR-T anti-CD19 cells was higher than that by CAR-T NKG2D. The absence of NKG2D proliferating CAR-T cells in mice peripheral blood confirms their low persistence. IFN-γ concentration in mice auto-plasma was 11.89 pcg/mL after CAR-T anti-CD19 infusion and 0.57 pcg/mL after CAR-T NKG2D infusion (= 0.0079). The mean weight of tumor xenografts in experimental groups 10 days after CAR-T anti-CD19 injection was 0.72 g (= 0.0142), after Т-lymphocyte and NKG2D CAR-T cell infusions it was 2.12 g and 1.2 g, respectively.

Conclusion. CAR-T anti-CD19 cells are characterized by more pronounced cytotoxic effect under both in vitro and in vivo experimental conditions compared with CAR-T NKG2D cells. The degree of CAR-T anti-CD19 proliferation and their infiltration in mice xenograft models is considerably higher than the levels reached with NKG2D CAR-T cell injections. A single CAR-T NKG2D injection results only in short-term tumor reduction.

Keywords: CAR-T cell therapy, NKG2D chimeric antigen receptor, co-stimulatory domains, NKG2D ligands, cytotoxic effect, CAR-T infiltration, CAR-T persistence.

Received: June 27, 2022

Accepted: September 12, 2022

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A Current View on Pathogenesis, Diagnosis, and Treatment of Some Rare Acute Leukemia Variants

OYu Baranova, AD Shirin

NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Olga Yurevna Baranova, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(925)837-27-08; e-mail: baranova-crc@mail.ru

For citation: Baranova OYu, Shirin AD. A Current View on Pathogenesis, Diagnosis, and Treatment of Some Rare Acute Leukemia Variants. Clinical oncohematology. 2022;15(4):307–26. (In Russ).

DOI: 10.21320/2500-2139-2022-15-4-307-326


ABSTRACT

Fundamental discoveries in immunobiology of normal hematopoiesis, emerging views on malignant growth mechanisms together with further improvement of diagnostic capabilities led to a crucial change in perception of leukemiology as one of separate important areas of modern clinical oncohematology. The now available detailed molecular genetic classification of acute leukemias is being complemented by new disease variants. New categories of acute leukemias and progenitor cell tumors have been identified. Nevertheless, many issues related to pathogenesis and classification of some variants of this heterogeneous disease remain unsolved and require further study. The present review provides thorough analysis of some rare variants of acute leukemias which are particularly challenging in terms of pathogenesis, diagnosis, and choice of treatment.

Keywords: rare acute leukemia variants, blastic plasmacytoid dendritic cell neoplasm, early T-cell precursor acute lymphoblastic leukemia, acute leukemias of indeterminate lineage, pure erythroid leukemia, lineage switch.

Received: June 2, 2022

Accepted: September 1, 2022

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Статистика Plumx английский

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