AUTOIMMUNE THROMBOCYTOPENIA

Acute Myeloid Leukemia Patient-Derived Xenograft Models Generated with the Use of Immunodeficient NSG-SGM3 Mice

AUTOIMMUNE THROMBOCYTOPENIA

EV Baidyuk1, EV Belotserkovskaya1, LL Girshova1,2, VA Golotin1, KA Levchuk2, ML Vasyutina2, YaA Portnaya1, EV Shchelina2, OG Bredneva2, AV Petukhov1,2,3, AYu Zaritskey2, ON Demidov1,3

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

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

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

For correspondence: Ekaterina Viktorovna Baidyuk, PhD in Biology, 4 Tikhoretskii pr-t, Saint Petersburg, Russian Federation, 194064; e-mail: katya_bay@mail.ru; Ekaterina Vasilevna Belotserkovskaya, PhD in Biology, 4 Tikhoretskii pr-t, Saint Petersburg, Russian Federation, 194064; e-mail: belotserkovskaya.ev@gmail.com

For citation: Baidyuk EV, Belotserkovskaya EV, Girshova LL, et al. Acute Myeloid Leukemia Patient-Derived Xenograft Models Generated with the Use of Immunodeficient NSG-SGM3 Mice. Clinical oncohematology. 2021;14(4):414–25. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-414-425

ABSTRACT

Background. Up to the present the survival rates of acute myeloid leukemia (AML) patients have remained low. A successful OML management presupposes generating personalized models of the disease. The most promising research activity in this field is creation of AML patient-derived xenograft models using the advanced strain of immunodeficient humanized NSG-SGM3 mice.

Aim. To generate AML patient-derived xenograft models using immunodeficient NSG-SGM3 mice.

Materials & Methods. The creation of PDX models was based on bone marrow aspirates taken from 4 patients with newly diagnosed AML who were treated at the VA Almazov National Medical Research Center. Patient-derived tumor cells were transplanted to NSG-SGM3 mice. Test experiment consisted in injecting AML cells OCI-АМL2 and HL60 in NSG-SGM3 mice. The efficacy of tumor engraftment was evaluated in terms of physical condition of animals and laboratory tests (blood count, blood smear, PCR, and flow cytofluorometry).

Results. The engraftment of applied tumor cells derived from 4 AML patients was achieved in half (2 out of 4) of the mice. In 2 mice with successful transplantation leukocytosis was reported. Blast cells were identified in peripheral blood on Day 30 after transplantation. The mice with injected AML cells OCI-АМL2 and HL60 showed a more aggressive course of disease. Among tested approaches to evaluate tumor engraftment in mouse recipients, the PCR method was marked by highest sensitivity.

Conclusion. The use of immunodeficient humanized NSG-SGM3 mice enables successful generation of AML patient-derived xenograft models.

Keywords: xenograft model, immunodeficient humanized mice, AML, NSG-SGM3 mice.

Received: April 27, 2021

Accepted: August 1, 2021

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Technical Aspects of Minimal Residual Disease Detection by Multicolor Flow Cytometry in Acute Myeloid Leukemia Patients

AUTOIMMUNE THROMBOCYTOPENIA , ,

IV Galtseva, YuO Davydova, NM Kapranov, KA Nikiforova, EN Parovichnikova

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

For correspondence: Yuliya Olegovna Davydova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: 8(495)612-62-21; e-mail: juliya89mur@yandex.ru

For citation: Galtseva IV, Davydova YuO, Kapranov NM, et al. Technical Aspects of Minimal Residual Disease Detection by Multicolor Flow Cytometry in Acute Myeloid Leukemia Patients. Clinical oncohematology. 2021;14(3):503–12. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-503-512

ABSTRACT

Detection and monitoring of minimal residual disease (MRD) are essential components of programmed therapy.They are crucial for the choice of treatment strategy and for prognostic purposes practically in all hematologic diseases. MRD is often detected by multicolor flow cytometry, the method with fairly high specificity and sensitivity. However, to identify MRD in acute myeloid leukemia patients is one of the most challenging tasks flow cytometry specialists are faced with. Cytometric data analysis requires the expert knowledge of immunophenotype of all maturing bone marrow cells. Besides, MRD analysis in acute myeloid leukemia has not been standardized while approaches suggested by different studies vary considerably. The present paper reports the experience of MRD analysis, demonstrates the gating strategy, immunophenotype description of normal non-tumor hematopoietic cells, and presents some examples of MRD assessment. Additionally, panels of monoclonal antibodies are provided, along with an evaluation of their advantages and disadvantages.

Keywords: minimal residual disease, acute myeloid leukemias, flow cytometry, gating, immunophenotyping.

Received: June 9, 2021

Accepted: September 5, 2021

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Carmustine in the Therapy of B-Cell Lymphomas

AUTOIMMUNE THROMBOCYTOPENIA , , ,

DA Koroleva, EE Zvonkov

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

For correspondence: Daria Aleksandrovna Koroleva, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-44-72; e-mail: koroleva_12-12@mail.ru

For citation: Koroleva DA, Zvonkov EE. Carmustine in the Therapy of B-Cell Lymphomas. 2021;14(4):496–502. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-496-502

ABSTRACT

Aim. To analyze the efficacy and toxicity of different high-dose chemotherapy protocols for the purpose of determining the optimal conditioning regimen with autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The present review provides the analysis of some comparative retrospective studies. The evidence-based analysis proceeded in two stages consisting of a search and then primary processing of available literature. The PubMed database was searched for publications for the period 2004–2020.

Results. In relapsed and refractory non-Hodgkin’s lymphomas as well as in Hodgkin’s lymphoma, the literature analysis demonstrated satisfactory efficacy of carmustine as part of BEAM conditioning. With the use of the BEAM conditioning regimen with subsequent auto-HSCT, up to 50 % of complete remissions were achieved in patients with non-Hodgkin’s lymphomas and up to 70 % in patients with Hodgkin’s lymphoma. Comparative studies show that despite concerns about severe toxicity, the use of carmustine was not associated with an increase in the incidence of adverse events. Lung and liver toxicity proved to be comparable with that of being observed while using alternative programs of high-dose chemotherapy and corresponded to 9 % and 6 % on LEAM and BEAM regimens, respectively. Besides, carmustine feasibility in primary diffuse large B-cell CNS lymphoma was considered and analyzed in the context of the lack of thiotepa.

Conclusion. High efficacy of carmustine as part of BEAM conditioning with subsequent auto-HSCT was proved in extremely unfavorable patients with relapsed and refractory non-Hodgkin’s lymphomas and Hodgkin’s lymphoma with an acceptable toxicity profile. The study of carmustine in the therapy of primary CNS lymphoma seems to be аn important area of clinical studies aimed at developing rational treatment options.

Keywords: carmustine, non-Hodgkin’s lymphomas, Hodgkin’s lymphoma, auto-HSCT, lomustine, thiotepa, primary diffuse large B-cell CNS lymphoma.

Received: July 15, 2021

Accepted: September 10, 2021

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Ibrutinib as First-Line Therapy in High-Risk Chronic Lymphocytic Leukemia: Case Reports

AUTOIMMUNE THROMBOCYTOPENIA , ,

NV Kurkina, EA Repina

NP Ogarev National Research Mordovia State University, 68 Bolshevistskaya str., Saransk, Russian Federation, 430005

For correspondence: Nadezhda Viktorovna Kurkina, MD, PhD, 26А Ul’yanova str., Saransk, Russian Federation, 430032; Tel.: +7(927)172-48-63; e-mail: nadya.kurckina@yandex.ru

For citation: Kurkina NV, Repina EA. Ibrutinib as First-Line Therapy in High-Risk Chronic Lymphocytic Leukemia: Case Reports. Clinical oncohematology. 2021;14(4):488–95. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-488-495

ABSTRACT

In the selection of the optimal specific therapy in chronic lymphocytic leukemia (CLL), a crucial role is played by the determination of risk groups. The CLL International Prognostic Index takes account of unfavorable del(17p), del(11q) cytogenetic abnormalities, and/or TP53 gene mutations as well as the mutation status of immunoglobulin heavy chain variable region genes (IGHV). The absence of IGHV gene mutations is often associated with such prognostically unfavorable genetic markers as del(17p), del(11q), trisomy 12, and TP53 mutation. The combinations of this kind affect the prognosis and overall survival rate. Besides, in high-risk CLL the efficacy of therapy is rather low and the development of refractoriness is possible. In such patients the use of Bruton tyrosine kinase inhibitor as first-line therapy considerably increases the probability of long-term remission. The present paper provides the analysis of clinical and hematological efficacy and tolerance of ibrutinib as first-line therapy in high-risk CLL. Ibrutinib shows high efficacy and low toxicity. The use of ibrutinib as first-line therapy effectively reduces the probability of CLL progression, which is especially critical in high-risk patients, i.e., with 17p deletion and TP53 gene mutation.

Keywords: chronic lymphocytic leukemia, high-risk group, 17p deletion, TP53 gene mutation, ibrutinib, efficacy, toxicity.

Received: March 15, 2021

Accepted: August 30, 2021

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REFERENCES

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  14. Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib Regimens versus Chemoimmunotherapy in Older Patients with Untreated CLL. N Engl J Med. 2018;379(26):2517–28. doi: 10.1056/NEJMoa1812836.

Systemic Т-Cell Lymphoproliferative Disease Associated with Epstein-Barr Virus: A Literature Review and a Case Report

AUTOIMMUNE THROMBOCYTOPENIA , ,

EA Shalamova, AM Kovrigina, IA Shupletsova, EE Nikulina, VD Latyshev, NV Tsvetaeva

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

For correspondence: Alla Mikhailovna Kovrigina, PhD in Biology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: kovrigina.alla@gmail.com

For citation: Shalamova EA, Kovrigina AM, Shupletsova IA, et al. Systemic Т-Cell Lymphoproliferative Disease Associated with Epstein-Barr Virus: A Literature Review and a Case Report. Clinical oncohematology. 2021;14(4):477–87. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-477-487

ABSTRACT

Epstein-Barr virus (EBV) is ubiquitous, being identified in 90–95 % of adults. Its reactivation in immunodeficiency conditions often leads to clonal transformation of В-lymphocytes and development of В-cell lymphoproliferative diseases (LPD) and В-cell lymphomas. At the same time, in the countries of North-East and East Asia, as well as Latin America, non-immunocompromised patients sometimes demonstrate the development of EBV-associated Т-cell lymphoproliferative diseases. The present paper reports a rare case of EBV-associated systemic T-LPD with lymphadenopathy, splenomegaly as well as acute autoimmune hemolytic anemia in a man of Caucasian race. Complex analysis of anamnestic, pathomorphological, and laboratory data allowed to distinguish this disease from Т-cell lymphoma and choose the appropriate patient management strategy.

Keywords: lymphoproliferative disease, Epstein-Barr virus, EBV+ T-LPD, diagnosis, pathomorphology.

Received: May 30, 2021

Accepted: September 2, 2021

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REFERENCES

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Prediction of Treatment Efficacy in Relapsed Chronic Lymphocytic Leukemia

AUTOIMMUNE THROMBOCYTOPENIA

OB Kalashnikova, IS Moiseev, TL Gindina, EA Izmailova, MO Ivanova, EV Kondakova, NB Mikhailova, AD Kulagin

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

For correspondence: Olga Borisovna Kalashnikova, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; e-mail: o4290@yandex.ru

For citation: Kalashnikova OB, Moiseev IS, Gindina TL, et al. Prediction of Treatment Efficacy in Relapsed Chronic Lymphocytic Leukemia. Clinical oncohematology. 2021;14(4):466–76. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-466-476

ABSTRACT

Background. The emergence of signaling pathway inhibitors (SPI) considerably improved the prognosis in relapsed chronic lymphocytic leukemia (R-CLL). Nevertheless, some patients cannot achieve optimal and sustained response. TP53 gene defects determine the refractoriness to immunochemotherapy (ICT) and lower rates of progression-free survival on SPI therapy. However, the prognostic value of complex karyotype (CK) in CLL has long been disputed. In recent years, greater attention has been placed on the prognostic impact of CK in the context of SPI therapy.

Materials & Methods. The study included 180 patients who received the drug treatment for R-CLL (113 of them with ICT, 67 of them with SPI). Their age at the onset of second-line therapy, the response to first-line therapy, early (< 24 months) progression after first-line therapy, the number of therapy lines, and the presence of CK and TP53 gene defect were regarded as prognostic markers. Taking into account the clonal evolution in CLL, to assess the significance degree of the above predictors, Cox proportional hazards regression model with time-dependent variables was used.

Results. The following independent factors proved to significantly reduce the risk of death: response achieved immediately after first-line therapy (hazard ratio [HR] 0.38; 95% confidence interval [95% CI] 0.20–0.72; p = 0.003) and the number of therapy lines (HR 0.56; 95% CI 0.37–0.86; p = 0.008). Treatment with only ICT in first and subsequent lines was associated with increasing risk of death (HR 2.25; 95% CI 1.09–4.63; p = 0.028). Genetic risks worsened the prognosis to a high degree of significance in the case of TP53 gene defect with excluded or unknown CK status (HR 10.54; 95% CI 4.25–26.17; p < 0.001) as well as in the case of CK (HR 14.08; 95% CI 5.77–34.35; p < 0.001). A significant predictor of poor outcome was reported to be the factor of unknown CK status without TP53 gene defect (HR 4.15; 95% CI 1.72–10.00; p = 0.002). Neither relapse time after first-line therapy nor the age ≥ 65 years showed independent prognostic value.

Conclusion. Standard karyotyping of peripheral lymphocytes with specific stimulation establishes a clearer disease prognosis and suggests the optimal choice of R-CLL treatment strategy.

Keywords: chronic lymphocytic leukemia, response predictors, del(17p), TP53 mutations, complex karyotype, cytogenetic risk, immunochemotherapy, ibrutinib, venetoclax.

Received: March 29, 2021

Accepted: August 15, 2021

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Статистика Plumx английский

REFERENCES

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Results of the Russian Multi-Center Cooperative Prospective-Retrospective Observational Program for Hodgkin’s Lymphoma Treatment RNWOHG-HD1

AUTOIMMUNE THROMBOCYTOPENIA ,

IS Moiseev1, SM Alekseev2,24, NB Mikhailova1, KD Kaplanov3,21, MV Demchenkova4, LV Anchukova5, VV Baikov1, AM Belyaev2, YuA Vasil’eva6, NP Volkov1, YuN Vinogradova7, AYu Zaritskey8, AE Zdorov9, NV Il’in7, LO Kashintseva10, EV Kondakova1, PV Kotselyabina1, VA Lapin11, KV Lepik1, IV Lesechko12, VM Moiseenko13, GM Manikhas14, NV Medvedeva15, YuA Oleinik2, ES Pavlyuchenko16, KS Parfenova17, EV Patrakova18, AV Proidakov19, DV Saidullaeva20, EV Tarasova21, AL Shipaeva22, TV Shneider23, BV Afanasyev1

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

2 NN Petrov National Medical Cancer Research Center, 68 Leningradskaya str., Pesochnyi settlement, Saint Petersburg, Russian Federation, 197758

3 SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

4 Regional Oncology Dispensary, 32 Frunze str., Irkutsk, Russian Federation, 664035

5 Vologda Regional Clinical Hospital, 17 Lechebnaya str., Vologda, Russian Federation, 160002

6 Pskov Oncology Dispensary, 15a Vokzalnaya str., Pskov, Russian Federation, 180004

7 AM Granov Russian Research Centre for Radiology and Surgical Technologies, 70 Leningradskaya str., Pesochnyi settlement, Saint Petersburg, Russian Federation, 197758

8 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

9 VA Baranov Republican Hospital, 3 Pirogova str. (Perevalka district), Petrozavodsk, Republic of Karelia, Russian Federation, 185002

10 Tula Regional Clinical Hospital, 1a Yablochkova str., Tula, Russian Federation, 300053

11 Yaroslavl Regional Clinical Hospital, 7 Yakovlevskaya str., Yaroslavl, Russian Federation, 150062

12 Stavropol Krai Clinical Oncology Dispensary, 182a Oktyabrskaya str., Stavropol, Russian Federation, 355047

13 Saint Petersburg Clinical Applied Research Center for Specialized Types of Medical Care (Oncology), 68A Leningradskaya str., Pesochnyi settlement, Saint Petersburg, Russian Federation, 197758

14 Municipal Clinical Oncology Dispensary, 3/5 2-ya Berezovaya alley, Saint Petersburg, Russian Federation, 197022

15 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

16 EE Eikhvald Clinic, II Mechnikov North-Western State Medical University, 41 bld. 7 Kirochnaya str., Saint Petersburg, Russian Federation, 191123

17 Samara Regional Clinical Oncology Dispensary, 11 Solnechnaya str., Syzran, Russian Federation, 446020

18 Vologda Regional Clinical Hospital No. 2, 15 Danilova str., Cherepovets, Vologda Region, Russian Federation, 162602

19 Komi Republican Oncology Dispensary, 46 Nyuvchimskoe sh., Krasnozatonskii town settlement, Syktyvkar, Republic of Komi, Russian Federation, 167904

20 Tver Regional Oncology Dispensary, 57/37 15 let Oktyabrya str., Tver, Russian Federation, 170008

21 First Republican Clinical Hospital, 57 Votkinskoe sh., Izhevsk, Russian Federation, 426039

22 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

23 Leningrad Regional Clinical Hospital, 45 bld. 2A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

24 LD Roman Leningrad Regional Clinical Oncology Dispensary, 2 Zaozernaya str., Kuzmolovskii settlement, Vsevolozhskii district, Leningrad Region, Russian Federation, 188663

For correspondence: Ivan Sergeevich Moiseev, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: 8(812)338-62-65; e-mail: moisiv@mail.ru

For citation: Moiseev IS, Alekseev SM, Mikhailova NB, et al. Results of the Russian Multi-Center Cooperative Prospective-Retrospective Observational Program for Hodgkin’s Lymphoma Treatment RNWOHG-HD1. Clinical oncohematology. 2021;14(4):455–65. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-455-465

ABSTRACT

Aim. The observational program was aimed at obtaining data on classical Hodgkin’s lymphoma (cHL) incidence in the Russian Federation, therapy options, and clinical outcomes of treatment. The aim of the prospective part of the program was to standardize the approaches to therapy and to compare its outcomes with off-protocol treatment.

Materials & Methods. The prospective-retrospective observational program for Hodgkin’s lymphoma treatment engaged 32 regional and federal centers. It included 218 patients, 21 out of them were included into the prospective part of the RNWOHG-HD1 (Russian North-West Oncology and Hematology Group — Hodgkin Disease Study 1) program. The median age was 36 years (range 22–87 years). cHL stages I/II were identified in 48 % of patients, III/IV stages were reported in 52 % of patients. The prospective part of the program used escalating protocol in patients with stages I/IIA and without risk factors and de-escalating protocol in patients with advanced stages. Overall (OS) and progression-free (PFS) survivals were analyzed in 160 and 152 patients, respectively. PET-CT was used to assess the response in 33 % of patients.

Results. The study used the following first-line chemotherapy regimens: ABVD in 42 %, BEACOPPst in 11 %, BEACOPP-14 in 17 %, BEACOPPesc in 25 %, and EACOPP in 1 % of cases. After the completion of first-line therapy objective response rate was 91 % including 61 % of complete responses. Response structure did not significantly differ in the groups of non-intensive therapy (ABVD and BEACOPPst), intensified regimens (BEACOPP-14, BEACOPPesc, and EACOPP), and treatment according to the RNWOHG-HD1 protocol (91 %, 92 %, and 96 %, respectively; p = 0.7226). In the total cohort the 3-year OS was 97 % (95% confidence interval [95% CI] 94–99 %), PFS was 87 % (95% CI 80–92 %). The 3-year PFS did not differ in ABVD, BEACOPPst, BEACOPP-14, BEACOPPesc, and RNWOHG-HD1 recipients (p = 0.37). International Prognostic Score (IPS) yielded significant results in PFS prediction for patients with IPS score of 5–6, but not for those with IPS score of 1–4 (p = 0.0028).

Conclusion. The observational program showed that the majority of participating centers use the risk-adapted ABVD/BEACOPPesc approach which explains no difference in PFS being found with the use of these chemotherapy options. The study demonstrated the need for PET-CT to assess the response since the CT alone cannot distinguish between complete and partial responses in a considerable number of patients. The prospective unified program for cHL treatment may well be implemented in the Russian Federation.

Keywords: classical Hodgkin’s lymphoma, multi-center study, ABVD, BEACOPP, positron emission tomography, risk-adapted therapy.

Received: May 25, 2021

Accepted: August 30, 2021

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Langerhans Cell Histiocytosis in Adults: Treatment Opportunities of Today

AUTOIMMUNE THROMBOCYTOPENIA

VD Latyshev, EA Lukina

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

For correspondence: Vitalii Dmitrievich Latyshev, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: LatyshevVD@gmail.com

For citation: Latyshev VD, Lukina EA. Langerhans Cell Histiocytosis in Adults: Treatment Opportunities of Today. Clinical oncohematology. 2021;14(4):444–54. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-444-454

ABSTRACT

Langerhans cell histiocytosis (LCH) is an extremely rare disease associated with tissue infiltration by pathological cells which are phenotypically similar to normal Langerhans cells. Standard therapy of LCH in adults has not been developed so far, due to the lack of sufficient evidence base for different treatment methods. In clinical practice, cytostatic treatment is applied along with new approaches using signaling pathway inhibitors involved in LCH pathogenesis. This literature review covers currently existing methods of LCH therapy in adults and their feasibility in clinical practice.

Keywords: Langerhans cell histiocytosis, treatment of histiocytosis, BRAFV600E mutation, MAPK.

Received: July 20, 2021

Accepted: September 23, 2021

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Статистика Plumx английский

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Molecular Profiling and Minimal Residual Disease Monitoring in Multiple Myeloma Patients: A Literature Review

AUTOIMMUNE THROMBOCYTOPENIA

AV Semyanikhina1,2, EE Tolstykh1

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

2 NP Bochkov Research Centre for Medical Genetics, 1 Moskvorech’e str., Moscow, Russian Federation, 115522

For correspondence: Aleksandra Vladimirovna Semyanikhina, MD, PhD, 23 Kashirskoye sh., Moscow, Russian Federation, Российская Федерация, 115478; Tel.: +7(926)371-21-56; e-mail: alexandra_silina@mail.ru

For citation: Semyanikhina AV, Tolstykh EE. Molecular Profiling and Minimal Residual Disease Monitoring in Multiple Myeloma Patients: A Literature Review. Clinical oncohematology. 2021;14(4):436–43. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-436-443

ABSTRACT

A personalized approach is a promising tool for malignant neoplasm (MN) treatment. Gaining success and benefit assessment of this approach were considerably facilitated by the implementation of the new generation sequencing techniques which allow to obtain comprehensive information on the tumor genome and transcriptome state with identifying potential biomarkers and targets for directed drug action. Despite the exponential growth in the number of sequenced tumor genomes, some of them are not subject of active clinical studies, although obviously and increasingly require optimization of current treatment regimens. One of these pathologies is multiple myeloma (MM). Considerable advances in its diagnosis and treatment have substantially increased survival rates. However, MM cannot be removed from the list of fatal diseases, yet. It is a neoplasm which needs to be further studied and explored for implementation of new treatment strategies, most of which would be based on pheno- and genotypic characteristics of tumor cells. The present review deals with the state of the art in the study of the MM molecular genetic profile, minimal residual disease (MRD) monitoring as well as potentials of the new generation sequencing for MRD diagnosis, prognosis, estimation, and search for predictors aimed at chemotherapy optimization.

Keywords: multiple myeloma, new generation sequencing, minimal residual disease.

Received: May 21, 2021

Accepted: August 29, 2021

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Статистика Plumx английский

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Biological Mechanisms of Sustaining Deep Molecular Response in Chronic Myeloid Leukemia Upon Withdrawal of Tyrosine Kinase Inhibitors

AUTOIMMUNE THROMBOCYTOPENIA ,

EYu Chelysheva, MA Guryanova, AG Turkina

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

For correspondence: Ekaterina Yurevna Chelysheva, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: denve@bk.ru

For citation: Chelysheva EYu, Guryanova MA, Turkina AG. Biological Mechanisms of Sustaining Deep Molecular Response in Chronic Myeloid Leukemia Upon Withdrawal of Tyrosine Kinase Inhibitors. Clinical oncohematology. 2021;14(4):427–35. (In Russ).

DOI: 10.21320/2500-2139-2021-14-4-427-435

ABSTRACT

The feasibility of treatment-free follow-up in chronic myeloid leukemia (CML) patients is an important issue in the era of tyrosine kinase inhibitors (TKI). The clinical trials of TKI withdrawal in case of a stable deep molecular response prove the probability of sustaining molecular remission in 40–60 % of patients. Treatment-free remission (TFR), even under persistence of residual leukemia cells, suggests that there are special biologically determined mechanisms of tumor cell proliferation control, which are independent of BCR-ABL kinase activity. The search for factors determining differences in residual leukemia clone kinetics upon TKI withdrawal is an objective which is crucial for understanding TFR as a new biological phenomenon. The review provides worldwide evidence dealing with the study of immunological, genetic, and other biological mechanisms underlying the control of minimal residual disease upon TKI discontinuation in CML patients.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, treatment-free remission, deep molecular response, minimal residual disease.

Received: May 10, 2021

Accepted: August 23, 2021

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Статистика Plumx английский

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