AUTOIMMUNE THROMBOCYTOPENIA

Following an Article Published in This Issue (a Letter to the Editors)

AUTOIMMUNE THROMBOCYTOPENIA

Глубокоуважаемый редактор!

В настоящем выпуске журнала «Клиническая онкогематология. Фундаментальные исследования и клиническая практика» помещена статья Е.В. Байдюк и соавт. «Создание ксенографтных моделей от больных острыми миелоидными лейкозами с использованием иммунодефицитных мышей линии NSG-SGM3» (с. ххх–хх). Авторы изучили возможность моделирования лейкоза человека в экспериментах по введению опухолевых клеток иммунодефицитным мышам. Считаю, что важность и своевременность исследования обусловливают необходимость обсуждения проблемы.

Не вызывает сомнений необходимость создания моделей опухолей человека in vivo. Эти модели наряду с бесклеточными системами и сериями культивируемых линий клеток — незаменимые объекты современных доклинических протоколов [1]. Адекватность и надежность таких моделей требуют критической оценки, однако невозможно переоценить важность клинико-лабораторной (гематологической) картины заболевания.

Наиболее существенный результат авторов статьи — установление возможности получения ксенотрансплантатов клеток острого миелоидного лейкоза (ОМЛ) у мышей. Показано долговременное (до 30 дней) выживание опухолевых клеток в кровотоке животных после однократной внутривенной инъекции пула фракционированных клеток, полученных от пациентов с ОМЛ. Авторы демонстрируют эффективность мониторинга лабораторных показателей у мышей-опухоленосителей; имеется возможность молекулярного исследования бластных клеток. Эффективность ксенотрансплантации показана на ограниченном клинико-экспериментальном материале, однако важность установления такой возможности заслуживает высокой оценки.

Современные подходы к моделированию опухолей системы крови включают химический канцерогенез, а также трансплантацию (гетеро- и ортотопическую) сингенных опухолевых клеток. Оба подхода позволяют получать важные результаты, однако наблюдение за лейкозными клетками человека, выживающими и пролиферирующими в кровотоке мыши, — существенный аспект. Именно с помощью таких моделей можно исследовать клетки конкретного пациента в соответствующем (с известной условностью) тканевом окружении.

Особенно перспективны ксенотрансплантаты для создания и испытания лекарственных средств: появляется возможность воздействовать на опухолевые клетки в приближенной к клинике ситуации. В последние годы эти модели позволили разработать новые лекарственные «кандидаты», вызывающие гибель лейкозных клеток с конкретными генетическими маркерами [1, 2]. Для таких исследований необходимо относительно длительное присутствие бластных клеток в организме. Важно, чтобы опухоль не вызвала гибель животного, поэтому требуется подбор дозировок и путей введения, комбинации препаратов и время для реализации терапевтического эффекта. Результаты Е.В. Байдюк и соавт. позволяют надеяться, что полученная модель адекватна этим требованиям.

Моделирование опухолевого процесса in vivo — трудоемкий и дорогостоящий процесс. Исследователь имеет дело со сложной биологической системой, поведение которой на существующем уровне знаний трудно предсказать. Авторы статьи справедливо отмечают недостаточность отдельных клинико-морфологических параметров лейкозных клеток для прогнозирования эффективности трансплантации. Эмпирический фактор и удача — спутники онколога-экспериментатора. Тем важнее организация проведенного исследования, приоритетного для отечественной науки и здравоохранения, и полученные авторами результаты.

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А.А. Штиль,

д-р мед. наук, заведующий лабораторией механизмов гибели опухолевых клеток ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России

Infectious Complications in Multiple Myeloma under Current Epidemiological Conditions: A Literature Review

AUTOIMMUNE THROMBOCYTOPENIA ,

IL Davydkin, EV Mordvinova, TP Kuzmina

Samara State Medical University, 89 Chapaevskaya str., Samara, Russian Federation, 443099

For correspondence: Elizaveta Vladimirovna Mordvinova, 89 Chapaevskaya str., Samara, Russian Federation, 443099; Tel.: +7(917)037-52-10, e-mail: liza.mordvinova.94@mail.ru

For citation: Davydkin IL, Mordvinova EV, Kuzmina TP. Infectious Complications in Multiple Myeloma under Current Epidemiological Conditions: A Literature Review. Clinical oncohematology. 2021;14(3):386–90. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-386-390

ABSTRACT

The review outlines current views on immune system in multiple myeloma (MM) and the basic pathogens inducing infectious complications in such patients. Although in recent years there has been considerable progress in studying molecular mechanisms of the MM development (pathogenesis), methods of its diagnosis, treatment, and prediction of outcomes, one of the main causes of death within this group of patients is infectious complications. In this context, it would be relevant to further study immune disorders and the spectrum of infectious pathogens common in the MM patient cohort. The study and correction of immunological status can contribute to improving the MM outcomes, which in turn will lead to increased life expectancy.

Keywords: multiple myeloma, immunological status, infectious complications, COVID-19.

Received: March 12, 2021

Accepted: June 8, 2021

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Статистика Plumx английский

REFERENCES

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Immune Reconstitution Inflammatory Syndrome and Hodgkin’s Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA

AV Pivnik1, AM Vukovich2, AA Petrenko3,4

1 SM Clinic, 42 bld. 12 Volgogradskii pr-t, Moscow, Russian Federation, 109548

2 IM Sechenov First Moscow State Medical University, 8 bld. 2 Trubetskaya str., Moscow, Russian Federation, 119991

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

4 Russian Medical Academy of Postgraduate Education, 2/1 Barrikadnaya str., Moscow, Russian Federation, 125993

For correspondence: Prof. Aleksandr Vasilevich Pivnik, MD, PhD, 42 bld. 12 Volgogradskii pr-t, Moscow, Russian Federation, 109548; Tel.: +7(906)065-99-32; e-mail: pivnikav@gmail.com

For citation: Pivnik AV, Vukovich AM, Petrenko AA. Immune Reconstitution Inflammatory Syndrome and Hodgkin’s Lymphoma. Clinical oncohematology. 2021;14(3):378–85. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-378-385

ABSTRACT

Immune reconstitution inflammatory syndrome (IRIS) is defined as a clinically significant exacerbation of known oligosymptomatic serious, more often infectious, diseases with considerably increased CD4+ T-lymphocyte count in response to highly active anti-retroviral therapy (HAART) of HIV infection. The review comprehensively discusses tuberculosis issues in HIV-positive HAART recipients. Related recommendations contain strict guidelines on compulsory treatment of tuberculosis prior to HAART assignment. Similar recommendations for specific therapy preceding HAART are provided for other opportunistic infections (mycotic and cryptococcal infections, parasitosis, molluscum contagiosum, toxoplasmosis, herpes-zoster virus, leishmaniasis, syphilis, and lepra). Without prior specific therapy of an opportunistic infection its exacerbation with pronounced symptoms and signs on HAART can be fatal for the patient. Lymphomas including Hodgkin’s lymphoma (HL) are dealt with in the context of the same challenge. However, what remains unclear is the specificity of targeted T-lymphocytes in the microenvironment to hitherto unclarified cause-specific antigens of the tumor. As opposed to other malignant lymphoid tumors arising with low level of CD4+ T-lymphocytes, HL develops when the level of CD4+ T-lymphocytes is increased in response to HAART in HIV-positive patients during the first months of anti-retroviral therapy. HL is diagnosed in 8 % of HIV-positive off-HAART subjects. After HAART assignment the HL incidence goes up to 17 %. Therefore, IRIS can be considered the main challenge in the study of etiology and pathogenesis of HL in HIV-positive patients. In this context, the demand to extend the research in this field becomes not only obvious but crucial for practical applications.

Keywords: immune reconstitution inflammatory syndrome (IRIS), highly active anti-retroviral therapy (HAART), Hodgkin’s lymphoma.

Received: January 19, 2021

Accepted: April 22, 2021

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Статистика Plumx английский

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Multiple Myeloma and Dendritic Cell Vaccines

AUTOIMMUNE THROMBOCYTOPENIA ,

IV Gribkova, AA Zavyalov

Research Institute for Healthcare Organization and Medical Management, 9 Sharikopodshipnikovskaya str., Moscow, Russian Federation, 115088

For correspondence: Irina Vladimirovna Gribkova, PhD in Biology, 9 Sharikopodshipnikovskaya str., Moscow, Russian Federation, 115088; Tel.: +7(916)078-73-90; e-mail: igribkova@yandex.ru

For citation: Gribkova IV, Zavyalov AA. Multiple Myeloma and Dendritic Cell Vaccines. Clinical oncohematology. 2021;14(3):370–7. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-370-377

ABSTRACT

Despite advances in the treatment of multiple myeloma, most of patients after its completion retain minimal residual disease (MRD-positive status), which increases the risk of relapse. Antigen-specific immunotherapy of tumors contributes to improving the clinical outcomes in such patients by the killing of cancer drug resistant clone of tumor cells without any damage to normal tissues. Dendritic cells (DC) are antigen-presenting elements with the main function of antigen-capturing, processing, and presenting them to naive T-lymphocytes for the activation of immune response against the captured antigen. The unique ability of DC to activate T-helpers and cytotoxic T-lymphocytes as well as to target thereby the immune reactions was used in developing DC-based tumor immunotherapy. This approach suggests the implementation of the so-called ‘DC-vaccines’. The clinical trials performed by now also showed the results of using DC-vaccines in various tumors including hematological ones. On the whole, according to the studies DC-vaccines are characterized by satisfactory safety profile, moderate immunological activity, and moderate clinical efficacy. The present review provides the results of clinical trials dealing with the use of DC-based vaccines in multiple myeloma patients. Besides, the potentials of improving the clinical efficacy of this therapy are discussed.

Keywords: multiple myeloma, dendritic cells, DC-vaccines, hematological malignancies, immunotherapy.

Received: March 9, 2021

Accepted: June 11, 2021

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Статистика Plumx английский

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Treatment of Mastocytosis: A Literature Review

AUTOIMMUNE THROMBOCYTOPENIA , ,

KM Chernavina1, AS Orlova1, EA Nikitin2

1 IM Sechenov First Moscow State Medical University, 8 bld. 2 Trubetskaya str., Moscow, Russian Federation, 119991

2 Russian Medical Academy of Postgraduate Education, 2/1 Barrikadnaya str., Moscow, Russian Federation, 125993

For correspondence: Karina Maksimovna Chernavina, 8 bld. 2 Trubetskaya str., Moscow, Russian Federation, 119992; e-mail: Shkyrlak@gmail.com

For citation: Chernavina KM, Orlova AS, Nikitin EA. Treatment of Mastocytosis: A Literature Review. Clinical oncohematology. 2021;14(3):361–9. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-361-369

ABSTRACT

The term “mastocytosis” refers to a group of rare heterogeneous disorders resulting from proliferation and accumulation of neoplastic mast cells in various organs. The World Health Organization (WHO) classifies these diseases into three types: cutaneous mastocytosis, systemic mastocytosis (SM), and mast cell sarcoma (MCS). Depending on the degree of aggressiveness SM can be indolent, smoldering, aggressive (ASM), or associated with another proliferative hematological disease of non-mast cell line (SM-AHD). SM also includes mast cell leukemia (MCL). Numerous studies confirm the prognostic value of the WHO classification. All mastocytosis patients require treatment aimed at reducing the symptoms of mast cell activation. In case of prognostically unfavorable types of mastocytosis, such as ASM, SM-AHD, MCL, and MCS, more intensive treatment methods should come into consideration, which include allogeneic hematopoietic stem cell transplantation, cytoreductive therapy with tyrosine kinase inhibitors (TKI), interferon-α, and cladribine. In the pathogenesis of mastocytosis, mutations in different KIT gene exons have a dominating role. Most common is KITD816V activating mutation (80–90 % of SM cases). Some of TKIs (imatinib mesylate and midostaurin) had been successfully used in clinical trials and were approved for treating prognostically unfavorable mastocytosis. However, in some patients exclusive TKI treatment does not result in long-lasting remission due to therapy resistance induced by KIT activating mutations as well as other additional somatic mutations and molecular changes. For the purpose of comparative analysis, the review provides the results of major clinical trials dealing with various methods of mastocytosis treatment.

Keywords: mast cells, mastocytosis, KITD816V mutation, targeted therapy, tyrosine kinase inhibitors, imatinib, midostaurin.

Received: March 12, 2021

Accepted: June 10, 2021

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Статистика Plumx английский

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Current Issues of Targeted Therapy of Polycythemia Vera

AUTOIMMUNE THROMBOCYTOPENIA , ,

AL Melikyan, IN Subortseva

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

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. Current Issues of Targeted Therapy of Polycythemia Vera. Clinical oncohematology. 2021;14(3):355–60. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-355-360

ABSTRACT

The issues of therapy response criteria, first-line hydroxycarbamide intolerance and resistance to it as well as early changes in treatment strategy remain controversial and debatable in the management of polycythemia vera patients. The review outlines the results of literature data analysis related to the estimation of first-line therapy efficacy, it considers the spectrum and frequency of adverse events of hydroxycarbamide treatment, and focuses on the experience of using ruxolitinib, JAK2 inhibitor. The review provides results, including the long-term ones, of the comparative analysis of ruxolitinib use and the best available therapy of polycythemia vera patients with hydroxycarbamide resistance. The present review uses the materials of expert panel with the participation of Prof. Giuseppe A. Palumbo (University of Catania, Sicily, Italy) held on June 7, 2020.

Keywords: polycythemia vera, JAK2V617F, prognosis, hydroxycarbamide, ruxolitinib.

Received: December 22, 2020

Accepted: May 10, 2021

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Статистика Plumx английский

REFERENCES

  1. Меликян А.Л., Туркина А.Г., Абдулкадыров К.М. и др. Клинические рекомендации по диагностике и терапии Ph-негативных миелопролиферативных заболеваний (истинная полицитемия, эссенциальная тромбоцитемия, первичный миелофиброз). Гематология и трансфузиология. 2014;59(4):31–56.
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Anemia of Chronic Diseases

AUTOIMMUNE THROMBOCYTOPENIA , , , ,

NV Kurkina, EI Gorshenina, LV Chegodaeva, AV Polagimova

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, Gorshenina EI, Chegodaeva LV, Polagimova AV. Anemia of Chronic Diseases. Clinical oncohematology. 2021;14(3):347–54. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-347-354

ABSTRACT

Anemia of chronic diseases (ACD) refers to a group of anemias arising in various inflammatory infections, autoimmune or tumor diseases due to acute or chronic immune activation. ACD ranks second in incidence after iron deficiency anemia (IDA). Within the variety of pathogenetic mechanisms one of the primary ones is hepcidin synthesis in hepatocytes, which blocks iron absorption in the intestine and contributes to its deposition in cells of the monocyte-macrophage system. Besides, excessive cytokines in such diseases and pathologies lead to lower erythropoietin production which does not correspond to the severity grade of anemia. This results in impaired erythropoiesis in the bone marrow. The differential diagnosis should also specify iron deficiency type (the absolute one in IDA and the functional one in ACD). The effective treatment of the main disease and anemia correction speed up the improvement of patient’s status, rehabilitation, and quality of life.

Keywords: anemia, chronic diseases, immune system, hepcidin, cytokines, erythropoietin, ferritin, serum iron.

Received: January 17, 2021

Accepted: April 30, 2021

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Статистика Plumx английский

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Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation

AUTOIMMUNE THROMBOCYTOPENIA , ,

SP Svitina, ZhYu Sidorova, II Kostroma, AA Zhernyakova, AV Chechetkin, ZhV Chubukina, SV Gritsaev, SI Kapustin, SS Bessmeltsev

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

For correspondence: Svetlana Pavlovna Svitina, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; e-mail: shvetikova@gmail.com

For citation: Svitina SP, Sidorova ZhYu, Kostroma II, et al. Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(3):340–6. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-340-346

ABSTRACT

Aim. To assess polymorphism value of interleukins (IL6, IL1B, IL10) and tumor necrosis factor α (TNF) genes in multiple myeloma (MM) patients who received autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The study enrolled 37 MM patients (15 men and 22 women) aged 38–66 years (mean age 54.5 ± 6.4 years), who received auto-HSCT. After transplantation, partial (PR), very good partial (VGPR), and complete (CR) responses were reported in 11, 7, and 19 patients, respectively. In 23 (62.2 %) patients CD34+ cell collection on the day of the first leukocytapheresis session exceeded the suboptimal level of 2.5 × 106/kg. The control group included 236 healthy subjects. Genotyping by PCR with subsequent analysis of restriction fragment length polymorphism of amplified products was performed. To identify between-group differences in genotype distribution, Fisher’s exact test with measurements of odds ratio (OR) and р–value was used.

Results. The study group of patients was distinguished from the control group by more than twofold increased proportion of homozygous IL1B –31C (OR 2.7; p = 0.029). The proportion of heterozygous –174G/C allelic variant of IL6 gene in the subgroup of patients with CR after auto-HSCT was considerably higher than in patients with VGPR and PR (OR 5.6; p = 0.022). In the subgroup of patients with CD34+ cell collection > 2.5 × 106/kg the proportion of those with IL10 –592C/C genotype was twice as high as in patients with lower CD34+ cell collection (OR 3.9; p = 0.091).

Conclusion. The present study confirms the relationship of –31C/Т polymorphism in IL1B gene in homozygous state with higher MM risk. It proved the association of –174G/C polymorphism in IL6 gene and –592C/A polymorphism in IL10 gene with the chosen criteria for auto-HSCT efficacy. To precisely clarify the value of variants in the above genes for predicting chemotherapy effect in MM, further studies involving more patients are required.

Keywords: multiple myeloma, genes polymorphism, immune response, cytokines, autologous hematopoietic stem cell transplantation.

Received: March 4, 2021

Accepted: June 10, 2021

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Статистика Plumx английский

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Potential Predictors and Response Quality after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma

AUTOIMMUNE THROMBOCYTOPENIA ,

II Kostroma1, ZhYu Sidorova1, NYu Semenova1, AA Zhernyakova1, RR Sabitova1, SP Svitina1, EI Stepchenkova2,3, SS Bessmeltsev1, AV Chechetkin1, SV Gritsaev1

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

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

3 NI Vavilov Institute of General Genetics, Saint Petersburg branch, 7/9 Universitetskaya emb., Saint Petersburg, Russian Federation, 199034

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(921)784-82-82; e-mail: obex@rambler.ru

For citation: Kostroma II, Sidorova ZhYu, Semenova NYu, et al. Potential Predictors and Response Quality after Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma. Clinical oncohematology. 2021;14(3):333–9. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-333-339

ABSTRACT

Aim. To assess the rate of cases without antitumor response quality improvement after high-dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM). To assess the rate of allelic variants of IL1B, IL6, IL10, TNF genes and the status of hematopoietic niche cells as potential predictors of auto-HSCT efficacy.

Materials & Methods. A retrospective analysis was based on the data of 84 MM patients who received 112 auto-HSCTs, including 84 first and 28 repeated courses. Response variants were estimated according to IWG criteria. Molecular profiling of IL1B, IL6, IL10, and TNF genes was performed using polymerase chain reaction (PCR) with subsequent analysis of restriction fragment length polymorphism of PCR products. To analyze the status of hematopoietic niche cells histological, immunohistochemical, and morphometric methods were applied.

Results. The first auto-HSCT yielded response quality improvement in 29 (54.7 %) out of 84 patients. The rate of complete response was significantly higher in patients who showed very good partial response before HDCT with auto-HSCT, than in patients with partial response (PR), i.e., 57.9 % and 18.2 %, respectively (р = 0.005). No differences were identified in the groups of patients with other clinical and hematological parameters. After the second auto-HSCT in 4 out of 6 patients with PR the response variant did not change. A significant decrease of MM activity was associated with IL6 (–174С) mutant allele carrier status of 81.3 % vs. 41.6 % in the group with the unchanged response variant (р = 0.05). Response quality improvement was also related to a large number of cells on the endosteum in histological specimens of bone marrow (р = 0.038).

Conclusion. The carrier status of IL6 (–174С) pathologic allele as well as the number of cells on the endosteum in histological specimens of bone marrow can be regarded as predictors of response quality improvement or lack thereof in MM patients after auto-HSCT.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, IL6 gene, hematopoietic niche.

Received: January 29, 2021

Accepted: May 30, 2021

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Pharmacoeconomic Analysis of R-DA-EPOCH and R-mNHL-BFM-90 Combination Immunochemotherapy in Patients with Prognostically Unfavorable Diffuse Large B-Cell Lymphoma within Randomized Multi-Center Clinical Trial DLBCL-2015

AUTOIMMUNE THROMBOCYTOPENIA

MO Bagova1, AU Magomedova1, SK Kravchenko1, RI Yagudina2, VG Serpik2, SM Kulikov1, YuA Chabaeva1

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

2 NA Semashko National Scientific Research Institute for Public Health, 12 bld. 1 Vorontsovo pole str., Moscow, Russian Federation, 105064

For correspondence: Madina Olegovna Bagova, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(938)913-43-83; e-mail: mbagova89@mail.ru

For citation: Bagova MO, Magomedova AU, Kravchenko SK, et al. Pharmacoeconomic Analysis of R-DA-EPOCH and R-mNHL-BFM-90 Combination Immunochemotherapy in Patients with Prognostically Unfavorable Diffuse Large B-Cell Lymphoma within Randomized Multi-Center Clinical Trial DLBCL-2015. Clinical oncohematology. 2021;14(3):321–32. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-321-332

ABSTRACT

Aim. Pharmacoeconomic analysis of R-DA-EPOCH and R-mNHL-BFM-90 combination immunochemotherapy in patients with prognostically unfavorable diffuse large B-cell lymphoma within randomized multi-center clinical trial DLBCL-2015.

Materials & Methods. The pharmacoeconomic analysis conducted between September 2018 and February 2020 was based on the treatment data of 22 patients enrolled in the DLBCL-2015 randomized multi-center clinical trial. This paper deals with the estimation of treatment outcomes in only one center, i.e., the National Research Center for Hematology. The R-DA-EPOCH induction therapy was administered to 14 out of 22 patients, 8 patients received the R-mNHL-BFM-90 block treatment. Within the R-DA-EPOCH group the second-line therapy was administered subsequently to 5 (36 %) out of 14 patients with partial remission or disease progression. The R-mNHL-BFM-90 treatment resulted in no need to assign second-line regimens. At the first stage, the efficacy of the compared induction therapy regimens was assessed. The next stage of the pharmacoeconomic study sought to analyze only the direct medical costs associated with the whole chemotherapy process. Further, the cost-effectiveness analysis was carried out, which allowed to estimate the financial resources necessary to achieve 1 case of complete remission (CR). A pharmacoeconomic decision-tree model was developed.

Results. CR was achieved in all 8 patients (100 %) who received the R-mNHL-BFM-90 block treatment. In the R-DA-EPOCH group CR was achieved only in 9 (64 %) out of 14 patients. The total mean cost of achieving 1 CR case per patient at all stages of diagnosis and chemotherapy with account for bed turnover (induction, second-line therapy, total supportive care) using R-mNHL-BFM-90 was 1,640,757 rubles, whereas in the R-DA-EPOCH group it was 1,469,878 rubles per patient. However, cumulative treatment costs of R-DA-EPOCH including chemotherapy of the second and further lines and supportive care were 2,896,519 rubles which exceeded those in the R-mNHL-BFM-90 group. Due to its higher efficacy the R-mNHL-BFM-90 immunochemotherapy precludes additional costs associated with both chemotherapy of the second and further lines and supportive care.

Conclusion. R-mNHL-BFM-90 as intensive induction block immunochemotherapy for DLBCL patients with poor prognosis is more effective than R-DA-EPOCH and allows to considerably reduce cumulative costs. It is possible due to complete preclusion of the costs of second-line chemotherapy and supportive care including blood component transfusions.

Keywords: diffuse large B-cell lymphoma, pharmacoeconomic analysis, cost-effectiveness analysis.

Received: March 26, 2021

Accepted: June 13, 2021

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