AUTOIMMUNE THROMBOCYTOPENIA

Familial Aggregation in Hodgkin’s Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA ,

SV Shakhtarina, AA Danilenko, NA Falaleeva

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

For correspondence: Svetlana Vasilevna Shakhtarina, MD, PhD, 4 Koroleva str., Obninsk, Kaluga Region, Russian Federation, 249036; Tel.: +7(484)399-31-01; e-mail: shakhtarina@mrrc.obninsk.ru

For citation: Shakhtarina SV, Danilenko AA, Falaleeva NA. Familial Aggregation in Hodgkin’s Lymphoma. Clinical oncohematology. 2021;14(2):193–7. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-193-197

ABSTRACT

Background. Genetic predisposition to Hodgkin’s lymphoma (HL) can be directly evidenced through observing familial HL. The literature data available on the familial aggregation samples of HL are extremely limited.

Aim. To systemize and assess observation data on familial aggregation in patients with classical HL based on the sequence of tumor development in blood relatives.

Materials & Methods. Data on families with HL diagnosed more than in one member were gathered from 4700 HL patients, who received chemotherapy from 1970 to 2019 at the AF Tsyb Medical Radiological Research Centre.

Results. Among the blood relatives 27 HL cases were identified, which amounted to 0.57 % of the total of 4700 patients. The families were arranged into four groups: group I with HL diagnosis in a child born before HL detection and treatment of a parent (15 families); group II with HL diagnosis in a child born after HL treatment of a parent (4 families); group III with HL diagnosis in several children of a family with lymphoma-free parents (6 families); group IV — other categories (2 families). The total number of HL patients was 54. Group I comprised 30 patients (15 children and 15 parents), group II included 8 parents (4 daughters and 4 mothers), group III consisted of 12 patients, and group IV included 4 patients.

Conclusion. The proportion of patients with familial aggregation of HL was 0.57 %. The age of all 54 HL patients enrolled in the study corresponded to the first age peak of HL onset. In the pairs “parent-child” children born before HL treatment of a parent accounted for 78.9 % and children born after HL treatment of a mother accounted for 21.1 % (all of them were girls). There were no HL cases in children born after HL treatment of a father. The data obtained show no effect of a parent’s chemotherapy on the occurrence of HL in a child. This is confirmed by the HL cases of siblings whose parents never received HL treatment as well as by the diagnosis of this malignant tumor first in a grandson and then in his grandmother.

Keywords: Hodgkin’s lymphoma, familial aggregation, children, parents.

Received: October 15, 2020

Accepted: February 1, 2021

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Ovary Lesions in Classical Hodgkin’s Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA

SYu Smirnova1, TN Moiseeva1, LS Al-Radi1, AB Fedorov2, SA Makhinya1, NV Volkov1, GA Yatsyk1, IA Shupletsova1, AM Kovrigina1

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

2 MEDSI Clinical Hospital, block 2 с1А Pyatnitskoe sh., 6th km, Moscow Region, Russian Federation, 123464

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: Smirnova SYu, Moiseeva TN, Al-Radi LS, et al. Ovary Lesions in Classical Hodgkin’s Lymphoma. Clinical oncohematology. 2021;14(2):188–92. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-188-192

ABSTRACT

Hodgkin’s lymphoma is a tumor characterized by predominant lesions in lymph nodes. Primary extranodal lesions are exceedingly rare. In the now available world literature, there are only single observations of classical Hodgkin’s lymphoma with ovary involvements. The present paper reports the diagnosis and treatment of a patient with classical Hodgkin’s lymphoma with ovary involvements confirmed by histological and immunohistochemical analyses.

Keywords: Hodgkin’s lymphoma, ovaries.

Received: September 22, 2020

Accepted: February 16, 2021

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Nivolumab in a Primary Refractory Hodgkin’s Lymphoma Patient with Absolute Lymphopenia Prior to Chemotherapy: Literature Review and a Case Report

AUTOIMMUNE THROMBOCYTOPENIA ,

TI Bogatyreva, AO Afanasov, NA Falaleeva, LYu Grivtsova, AYu Terekhova

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

For correspondence: Tatyana Ivanovna Bogatyreva, MD, PhD, 4 Koroleva str., Obninsk, Kaluga Region, Russian Federation, 249036; e-mail: bogatyreva@mrrc.obninsk.ru

For citation: Bogatyreva TI, Afanasov AO, Falaleeva NA, et al. Nivolumab in a Primary Refractory Hodgkin’s Lymphoma Patient with Absolute Lymphopenia Prior to Chemotherapy: Literature Review and a Case Report. Clinical oncohematology. 2021;14(2):179–87. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-179-187

ABSTRACT

The paper presents a case report of PET-adapted therapy of primary refractory classical Hodgkin’s lymphoma, stage IIАХ, in a female patient with absolute lymphopenia prior to chemotherapy. It also provides literature review on the choice of clinical management for similar categories of patients. Nivolumab was prescribed to the patient in February 2019 due to Hodgkin’s lymphoma progression after the failure of 4 chemotherapy lines including brentuximab vedotin. A bulk of mediastinal lymph nodes was exposed to radiation. Complete metabolic response was retained 18 months after nivolumab therapy start and 6 months after its discontinuation. The initial lymphopenia in this patient with primary refractory Hodgkin’s lymphoma did not interfere with the realization of full clinical effect of nivolumab.

Keywords: classical Hodgkin’s lymphoma, absolute lymphopenia, chemotherapy-refractory disease, immunotherapy, salvage therapy.

Received: September 9, 2020

Accepted: February 18, 2021

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Cytogenetic and Molecular Genetic Abnormalities of CIITA Gene in Patients with Primary Mediastinal (Thymic) Large B-Cell Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA

SA Kuznetsova, VL Surin, YaK Mangasarova, TYu Novikova, LA Grebenyuk, AU Magomedova, SK Kravchenko, OS Pshenichnikova, AM Sergeeva, TN Obukhova

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

For correspondence: Svetlana Aleksandrovna Kuznetsova, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(985)170-61-83; e-mail: svetakuznetsova83@mail.ru

For citation: Kuznetsova SA, Surin VL, Mangasarova YaK, et al. Cytogenetic and Molecular Genetic Abnormalities of CIITA Gene in Patients with Primary Mediastinal (Thymic) Large B-Cell Lymphoma. Clinical oncohematology. 2021;14(2):173–8. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-173-178

ABSTRACT

Background. Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is an aggressive malignant lymphoproliferative disease which accounts for 2–3 % of all non-Hodgkin’s lymphomas. In 40 % of PMBCL cases rearrangements of the MHC class II activator, i.e. CIITA gene, are observed. CIITA abnormalities lead to decreasing protein expression and surface expression of MHC class II, which results in lack of adaptive cell immunity targeted at tumor cells.

Aim. To assess the rate and spectrum of cytogenetic and molecular genetic abnormalities of CIITA gene in PMBCL patients.

Materials & Methods. The study enrolled 37 patients with diagnosed PMBCL: 10 men and 27 women aged 21–61 years (median of 31 years). Sanger sequencing was performed in 36 patients. In 20 patients CIITA/16p13.13 FISH and in 15 patients standard cytogenetic analysis were carried out.

Results. In 3 (8.3 %) out of 36 patients the sequencing method detected mutations impairing CIITA gene function, as well as microdeletion in exon 1, deletion and nucleotide substitution in a splice donor site. Multiple somatic variations in intron 1 were identified in 21 (58.3 %) patients: in 11 (52.4 %) cases there were deletions and single nucleotide variants (SNV); the other 10 (47.6 %) patients showed only SNVs. In 13 (61.9 %) out of 21 cases the abnormalities of promoter IV and/or alternative exon 1 were observed. In 5 (25 %) out of 20 patients the FISH assay identified CIITA gene translocation. Standard cytogenetic analysis detected complex karyotype in 7 (46.6 %) out of 15 patients. The comparison of data showed hypermutagenesis in 8 out of 10 patients with FISH-detected chromosome aberrations, and in 3 (37.5 %) of them complex karyotype aberrations were found as well.

Conclusion. Molecular genetic methods identified different somatic variations in CIITA gene affecting its functionally important regions, which can be of special interest for further studying the biology of tumors, including PMBCL.

Keywords: primary mediastinal (thymic) B-cell large cell lymphoma, CIITA, FISH, chromosomal aberrations, Sanger sequencing.

Received: December 15, 2020

Accepted: March 11, 2021

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Acute Myeloid Leukemia as Second Tumor in a Patient with Burkitt’s Lymphoma: Literature Review and a Case Report

AUTOIMMUNE THROMBOCYTOPENIA ,

TT Valiev1, TYu Pavlova1, AM Kovrigina2, IN Serebryakova1

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

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

For correspondence: Timur Teimurazovich Valiev, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail: timurvaliev@mail.ru

For citation: Valiev TT, Pavlova TYu, Kovrigina AM, Serebryakova IN. Acute Myeloid Leukemia as Second Tumor in a Patient with Burkitt’s Lymphoma: Literature Review and a Case Report. Clinical oncohematology. 2021;14(2):167–72. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-167-172

ABSTRACT

The application of highly effective tumor treatment protocols in children and increasing number of patients healed resulted in a growing focus on long-term effects of chemotherapy. One of the most dangerous complications of a first malignant neoplasm (MN) is the development of second MNs. Cytostatic drugs of the epipodophyllotoxin group and alkylating agents contribute to secondary acute myeloid leukemias (AML), the rare and prognostically very unfavorable second MNs. The present article provides a review of literature on risks of secondary hematological MNs associated with the therapy of first tumors. It also contains a case report of successful treatment of AML which occurred after Burkitt’s lymphoma therapy.

Keywords: second malignant neoplasms, acute myeloid leukemias, Burkitt’s lymphoma, children.

Received: December 10, 2020

Accepted: March 1, 2021

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Mastocytosis in Adults: A Retrospective Analysis of the Clinical Course and Treatment of 58 Patients

AUTOIMMUNE THROMBOCYTOPENIA ,

VG Potapenko1,2, VV Baikov2, IE Belousova3, EA Belyakova4, MV Barabanshchikova2, DV Zaslavsky5, IS Zyuzgin6, AV Klimovich1, YuA Krivolapov4, TG Kulibaba7, EV Lisukova2, EE Leenman4, LA Mazurok8, AM Maksimova3, EV Morozova2, AS Nizamutdinova9, KA Skoryukova1, EA Ukrainchenko9, NV Medvedeva1

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

2 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

3 SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

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

5 Saint-Petersburg State Pediatric Medical University, 2 Litovskaya str., Saint Petersburg, Russian Federation, 194100

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

7 Saint Petersburg State University, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

8 Kurgan Regional Clinical Hospital, 63 Tomina str., Kurgan, Russian Federation, 640002

9 Aleksandrov Hospital, 4 bld. 3 pr-t Solidarnosti, Saint Petersburg, Russian Federation, 193312

For correspondence: Vsevolod Gennadevich Potapenko, MD, PhD, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(905)284-51-38; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Baikov VV, Belousova IE, et al. Mastocytosis in Adults: A Retrospective Analysis of the Clinical Course and Treatment of 58 Patients. Clinical oncohematology. 2021;14(2):158–66. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-158-166

ABSTRACT

Background. Mastocytosis is a disease caused by proliferation and accumulation of clonal mast cells in one or more organs. It is often associated with other hematological tumors. Aggressive forms of mastocytosis (AFM) require specific therapy. In non-aggressive forms of mastocytosis (NFM) symptomatic treatment is needed. NFMs prevail, therefore, the disease often goes unrecognized.

Aim. To analyze the clinical course and treatment outcomes in different forms of adult mastocytosis.

Materials & Methods. The retrospective analysis was based on the records of patients who received in-person and distance consultation within the period from 11/2008 to 11/2020. The analysis of complaints in disease onset and over time was carried out using questionnaires. NFM patients received symptomatic treatment with antihistamines. To all AFM patients chemotherapy was administered.

Results. The analysis includes the data of 58 patients: 39 (67.2 %) women and 18 (32.8 %) men. The median age was 40 years (range 18–79 years), the median age on diagnosis was 39 years (range 1–79 years). In all patients skin rashes were reported. The median age of the first skin manifestations was 25 years (range 0.1–70 years). In-person monitoring was conducted in 34 (58.6 %) patients, 24 (41.4 %) patients received distance consultations. Median follow-up was 56.5 months (range 3–564 months). In 8 (13.7 %) patients mastocytosis was diagnosed in childhood with the median of 9 years (range 0–15 years). The diagnosis was morphologically confirmed in 46 (79.3 %) patients. Main complaints included pruritus (67.2 %), edema and erythema response to various irritants (62 %). In 45 (77.5 %) patients NFMs were reported. The regular symptomatic treatment of 78.8 % of NFM patients consisted only of antihistamines (57.9 %), and 2 (4.4 %) patients noted poor disease symptom control. One (2.2 %) patient died of associated chronic myelomonocytic leukemia. None of NFM patients required cytoreductive treatment. AFMs were diagnosed in 13 (22.4 %) patients, 5 (38.4 %) out of them had mast cell leukemia. The indications for starting chemotherapy were cytopenia (n = 3; 23 %), extensive osteolysis (n = 7; 53.8 %), ascitic syndrome with portal hypertension (n = 6; 46,1 %). Overall survival of AFM patients was 84.6 % (n = 11) with median follow-up of 80 months (range 12–131 months).

Conclusion. NFM prognosis is favorable. Antihistamines are effective in relieving complaints of most patients. Cytostatic treatment of AFM in some patients provides long-lasting antitumor response.

Keywords: mastocytosis, tryptase, mast cells, indolent mastocytosis, aggressive mastocytosis, С-KIT, cladribine, imatinib.

Received: December 13, 2020

Accepted: March 3, 2021

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In Memory of Prof. L.A. Makhonova

AUTOIMMUNE THROMBOCYTOPENIA

29 января 2021 г. ушла из жизни основоположник отечественной детской онкогематологии, заслуженный врач РФ, доктор медицинских наук, профессор Лидия Алексеевна Махонова.

Лидия Алексеевна была крупнейшим российским ученым, внесшим значительный вклад в становление и развитие клинической детской онкогематологии.

После окончания в 1949 г. 2-го Московского медицинского института им. Н.И. Пирогова (в настоящее время — Российский национальный исследовательский медицинский университет им. Н.И. Пирогова) работала врачом-педиатром, затем руководила терапевтическим отделением Московской детской больницы № 1. Многие годы клиническая работа Л.А. Махоновой была связана с диагностикой и лечением злокачественных опухолей кроветворной и лимфоидной тканей у детей.

Накопленный опыт и появление первых противоопухолевых препаратов, вызывающих противолейкемический эффект, стали основой кандидатской диссертации на тему: «Современные методы лечения острого лейкоза у детей», которую Лидия Алексеевна защитила в 1963 г. под руководством академика АМН СССР, основателя отечественной гематологии И.А. Кассирского. Важнейшим выводом работы стало положение о том, что при острых лейкозах у детей возможно получение ремиссии с помощью 6-меркаптопурина и преднизолона. Была подтверждена необходимость проведения поддерживающей терапии при острых лейкозах, а также обозначены оптимальные дозы и режимы назначения первых эффективных противоопухолевых препаратов.

Под эгидой кафедры факультетской педиатрии 2-го Московского медицинского института им. Н.И. Пирогова в 1964 г. Лидия Алексеевна организовала первое в нашей стране детское гематологическое отделение на базе Морозовской детской больницы в г. Москве. В новом отделении получали лечение дети с лейкозами, лимфомами, геморрагическим диатезом, анемией. Л.А. Махонова, будучи ярким и талантливым клиницистом, продолжала и развивала традиции отечественной клинико-морфологической гематологической школы. Ее клиническая деятельность не ограничивалась только оценкой особенностей лечения опухолей системы крови у детей. Она принимали активное личное участие в постановке диагноза на основании анализа цитологических препаратов костного мозга и лимфатических узлов. При непосредственном участии Лидии Алексеевны в 1960-е годы по сути были заложены основы новой дисциплины «Детская гематология» и начата профессиональная последипломная подготовка детских гематологов.

В 1960–1970-е годы Л.А. Махонова была главным детским гематологом МЗ РСФСР. Под ее непосредственным руководством заложены основы всей онкогематологической педиатрической службы в РСФСР.

Пристальный интерес у Л.А. Махоновой вызывали работы по поиску новых лекарственных препаратов, эффективных при острых лейкозах. Л.А. Махонова и ее коллеги (С.А. Маякова, И.Е. Гаврилова) в 1970-е годы активно исследовали иммунологические методы терапии. Оценивались противолейкемический эффект аллоиммунизации, роль и место препаратов интерферона в лечении острых лейкозов у детей. В 1973 г. Л.А. Махонова защитила докторскую диссертацию на тему: «Материалы к клинике и лечению (химиотерапия и иммунотерапия) острого лейкоза у детей».

Детская онкогематология еще только формировалась, стандарты лечения острых лейкозов у детей только начинали разрабатываться, а в названии докторской диссертации Л.А. Махоновой в 1973 г. уже звучало новое и перспективное направление противоопухолевого лечения — иммунотерапия. Такой подход с современных позиций можно признать как великий дар научного и клинического предвидения. Ведь сегодня онкогематологию, равно как и онкологию в целом, невозможно представить без достижений иммунотерапии.

А тогда… Как вспоминают соратники Лидии Алексеевны по борьбе с лейкозами, она вынесла тяжелые сражения с коллегами клиники для взрослых, отстаивая перспективность применения интерферонов при злокачественных опухолях системы крови. Смелый и беззаветно преданный лечению детей человек. Напрочь лишенный карьеризма, готовый в любую минуту броситься в бой за свои идеи, пусть даже еще только зарождающиеся, как было с иммунотерапией. Верность этому направлению она пронесла через всю жизнь. И в том, что мы сегодня видим, — настоящий триумф иммунологических подходов в лечении гематологических опухолей, огромная неоценимая заслуга Лидии Алексеевны Махоновой.

В 1976 г. Николай Николаевич Блохин пригласил Лидию Алексеевну возглавить детскую онкогематологическую службу во Всесоюзном онкологическом научном центре АМН СССР (ВОНЦ). Она руководила отделением детской онкогематологии в течение 17 лет, постоянно совершенствуясь в профессии и передавая богатейшие опыт и знания своим ученикам.

В 1980–1990-е годы Л.А. Махонова продолжает изучать и активно внедрять в клиническую практику новые лекарственные препараты и протоколы лечения лейкозов и лимфом у детей. Отделение детской химиотерапии гемобластозов ВОНЦ при непосредственном участии Лидии Алексеевны как руководителя одно из первых в России освоило методики терапии метотрексатом в высоких дозах, разработало принципы сопроводительной терапии и эффективные методы коррекции осложнений противоопухолевого лечения.

Л.А. Махонова, ее коллеги и ученики внесли основополагающий вклад в становление и развитие международного научного сотрудничества благодаря включению отделения химиотерапии гемобластозов НИИ детской онкологии и гематологии Российского онкологического научного центра им. Н.Н. Блохина РАМН (РОНЦ) в международную группу BFM (Berlin-Frankfurt-Munster) по лечению острого лимфобластного лейкоза у детей. До настоящего времени мы используем богатейший клинический и научный опыт Л.А. Махоновой. В отделении используются новые версии наиболее эффективных протоколов лечения острых лейкозов и лимфом у детей: ALL-IC BFM 2002, 2009, 2020; B-NHL-BFM 1995, 2004.

Всю свою профессиональную деятельность Л.А. Махонова особое внимание уделяла проблемам диагностики и лечения гистиоцитарных опухолей у детей и взрослых. Продолжая работу в РОНЦ им. Н.Н. Блохина до 2017 г., Лидия Алексеевна оказывала большую консультативную помощь в двух клинических институтах Центра: НИИ детской онкологии и гематологии и НИИ клинической онкологии им. Н.Н. Трапезникова. Благодаря Лидии Алексеевне в НИИ детской онкологии и гематологии ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России накоплен крупнейший в стране и мире клинический материал, отражающий лечение гистиоцитозов более чем у 1500 детей.

Л.А. Махонова — автор более 300 научных работ, в т. ч. монографий, методических руководств и рекомендаций. Руководитель 32 диссертаций на соискание ученой степени кандидата медицинских наук и 8 — доктора медицинских наук.

Лидия Алексеевна награждена медалью «За заслуги перед Отечеством» (2002), премией Правительства РФ за разработку и применение иммунокорректирующих препаратов (1997), премией РОНЦ им. Н.Н. Блохина за работу «Современная стратегия и результаты лечения лимфоидных опухолей у детей» (2005).

Л.А. Махонова была не только выдающимся врачом, исследователем, педагогом, но и мудрым наставником. Жизнь Л.А. Махоновой — пример беззаветного служения великому делу лечения тяжело больных детей с онкогематологическими заболеваниями.

 

Коллеги по работе и коллектив редакции

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CAR-T Technology and New Opportunities for Tumor Treatment

AUTOIMMUNE THROMBOCYTOPENIA

VYu Pavlova1, ES Livadnyi2

1 SV Belyaev Kemerovo Regional Clinical Hospital, 22 bld. 2 Oktyabrskii pr-t, Kemerovo, Russian Federation, 650066

2 Kemerovo State Medical University, 22a Voroshilova str., Kemerovo, Russian Federation, 650066

For correspondence: Vera Yurevna Pavlova, MD, PhD, 22 bld. 2 Oktyabrskii pr-t, Kemerovo, Russian Federation, 650066; Tel.: +7(951)570-57-86; e-mail: vera.4447.kem@mail.ru

For citation: Pavlova VYu, Livadnyi ES. CAR-T Technology and New Opportunities for Tumor Treatment. Clinical oncohematology. 2021;14(1):149–56. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-149-156

ABSTRACT

As a cause of death malignant neoplasms come in at the second place after cardiovascular disorders. CAR-T (chimeric antigen receptor of T-cells) therapy is an advanced malignant tumor treatment method. The use of CAR-T lymphocytes refers to adoptive immunotherapy. CAR-T technology is based on “extracting” immune cells (T-lymphocytes) and their genetic modification aimed at acquiring antitumor properties and followed by reinfusion. The advantage of CAR-T therapy in comparison to other treatment methods is that for target cell recognition T-lymphocytes are not dependent on major histocompatibility complex class 1 (MHC-I) molecules. The literature data we collected and analyzed show that this is a fundamentally new and effective treatment method of oncohematological diseases including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin’s lymphomas. Clinical trials proved the advantage of CAR-T therapy in comparison to other treatment methods applied in this field. The analysis of literature showed that CAR-T therapy can be reasonably regarded as one of the advanced opportunities for malignant tumor treatment.

Keywords: adoptive immunotherapy, CAR-T lymphocytes, chimeric antigen receptor.

Received: September 20, 2020

Accepted: December 1, 2020

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Статистика Plumx английский

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CAR T-Cell Therapy with NKG2D Chimeric Antigen Receptor in Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome

AUTOIMMUNE THROMBOCYTOPENIA

KA Levchuk1, EV Belotserkovskaya1,2, DYu Pozdnyakov1, LL Girshova1, AYu Zaritskey1, AV Petukhov1,2,3

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

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

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

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

For citation: Levchuk KA, Belotserkovskaya EV, Pozdnyakov DYu, et al. CAR T-Cell Therapy with NKG2D Chimeric Antigen Receptor in Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome. Clinical oncohematology. 2021;14(1):138–48. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-138-148

ABSTRACT

NK-cells as innate immunity elements manifest key reactions of antitumor immune response. NKG2D is an activating transmembrane receptor of NK-cells which is responsible for cytotoxicity initiation in response to the binding of specific ligands of genetically modified cells. Selective expression of NKG2D ligands provides a unique perspective on the therapy of wide variety of tumors. Acute myeloid leukemias (AML) are malignant hematological tumors with a high relapse risk. Due to the complexity of AML treatment strategy it is necessary to develop new approaches to tumor elimination using novel genetic constructs. Currently available CAR T-cell drugs with NKG2D receptor are successfully subjected to clinical studies in AML patients and prove their high therapeutic potential.

Keywords: acute myeloid leukemias, chimeric antigen receptor, adoptive therapy, NKG2D, NK-cells.

Received: August 22, 2020

Accepted: December 5, 2020

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Статистика Plumx английский

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Current View on Diagnosis and Treatment of Classical Ph-Negative Myeloproliferative Neoplasms

AUTOIMMUNE THROMBOCYTOPENIA , , , , ,

AL Melikyan1, IN Subortseva1, VA Shuvaev2,3, EG Lomaia4, EV Morozova5, LA Kuzmina1, OYu Vinogradova6,7,8, AYu Zaritskey4

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

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

3 VV Veresaev Municipal Clinical Hospital, 10 Lobnenskaya str., Moscow, Russian Federation, 127644

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

5 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

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

7 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117997

8 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Anait Levonovna Melikyan, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: anoblood@mail.ru

For citation: Melikyan AL, Subortseva IN, Shuvaev VA, et al. Current View on Diagnosis and Treatment of Classical Ph-Negative Myeloproliferative Neoplasms. Clinical oncohematology. 2021;14(1):129–37. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-129-137

ABSTRACT

Classical Ph-negative myeloproliferative neoplasms (MPN) constitute a group of diseases including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Over the past decade, the approaches to understanding of MPN pathogenesis and therapy have considerably changed. At the same time, etiological factors and pathophysiological mechanisms of disease progress are being thoroughly studied. The improvement of diagnosis methods and new approaches to therapy can reduce complications and mortality risks. The review outlines the current diagnosis methods, such as the molecular genetic one, and provides prognostic scores. Different methods of conservative therapy are assessed. Special attention is paid to quality of life measurement and targeted treatment of patients.

Keywords: myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia, primary myelofibrosis, JAK2V617F, CALR, MPL, prognosis, constitutional symptoms, MPN10, ruxolitinib.

Received: September 1, 2020

Accepted: December 10, 2020

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Статистика Plumx английский

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