AUTOIMMUNE THROMBOCYTOPENIA

Comparative Analysis of Myelofibrosis Treatment Outcomes with the Use of Ruxolitinib Versus Ruxolitinib with Subsequent Allogeneic Hematopoietic Stem Cell Transplantation

AUTOIMMUNE THROMBOCYTOPENIA ,

MV Barabanshchikova, EV Morozova, YuYu Vlasova, TL Gindina, AV Evdokimov, IM Barkhatov, VV Baikov, IO Ivanova, TA Rudakova, EA Bakin, IS Moiseev, AD Kulagin

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

For correspondence: Mariya Vladimirovna Barabanshchikova, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(911)164-01-57; e-mail: maria.barabanshikova.spb@gmail.com

For citation: Barabanshchikova MV, Morozova EV, Vlasova YuYu, et al. Comparative Analysis of Myelofibrosis Treatment Outcomes with the Use of Ruxolitinib Versus Ruxolitinib with Subsequent Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(1):22–30. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-22-30

ABSTRACT

Aim. To comparatively analyze myelofibrosis treatment outcomes with the use of ruxolitinib versus ruxolitinib with subsequent allogeneic hematopoietic stem cell transplantation (allo-HSCT) as well as to assess the efficacy of ruxolitinib in pre- and post-transplantation periods.

Materials & Methods. The study enrolled 78 myelofibrosis patients who were referred to the RM Gorbacheva Scientific Research Institute to determine the indications for allo-HSCT. Allo-HSCT was performed in 33 patients, among them 32 patients with ruxolitinib pre-conditioning (ruxolitinib + allo-HSCT group). They received reduced intensity conditioning (fludarabine 180 mg/m2 and busulfan 10 mg/kg). Graft-versus-host disease (GVHD) prophylaxis included cyclophosphamide 50 mg/kg on Day +3 and Day +4, ruxolitinib 10 mg per day from Day +5 to Day +100 (n = 31), rabbit antithymocyte globulin, tacrolimus, and mycophenolate mofetil (n = 2). Ruxolitinib without allo-HSCT was administered to 45 patients (ruxolitinib group). Between the groups there were no significant differences with respect to gender, age, diagnosis, and molecular genetic variant.

Results. Median therapy duration in ruxolitinib group was 16 months (range 2–78 months). In 2 (4 %) patients partial response was achieved, 8 (20 %) patients showed clinical improvement, in 16 (39 %) patients stable disease (SD) was reported, in 15 (37 %) patients disease progression (DP) was detected. The treatment succeeded in reducing the spleen size in 8 (20 %) patients and in relieving disease symptoms in 16 (39 %) patients. Cumulative incidence of progression within 3 years was 44 % (95% confidence interval [95% CI] 27–60 %). In ruxolitinib + allo-HSCT group median ruxolitinib therapy duration was 7 months (range 3–22 months.). As a result, clinical improvement in 9 (28 %) cases, SD in 17 cases (53 %), and DP in 6 (19 %) cases were observed. In 5 (20 %) patients acute GVHD of grade 2–4, in 3 (12 %) patients acute GVHD of grade 3–4, and in 6 (24 %) patients chronic medium severity GVHD were identified. Within 1 year non-relapse mortality was 28 % (95% CI 14–44 %). The 3-year cumulative incidence of relapse was 12 % (95% CI 3–28 %) in ruxolitinib + allo-HSCT group. According to the landmark analysis performed throughout 6 months from the first visit to the center, the 3-year overall survival in the group with allo-HSCT was 80 %, whereas in ruxolitinib group it was 41 % (p = 0.022), 12-month landmark analysis resulted in 77 % and 43 % (p = 0.028), and 18-month landmark analysis showed 86 % and 46 % (p = 0.015) in two groups, respectively.

Conclusion. Despite the efficacy of JAK1/2 inhibitor ruxolitinib, the risk of myelofibrosis progression is not to be underestimated. Therefore, in DIPSS intermediate-2 and high-risk patients the issue about performing allo-HSCT should be promptly clarified.

Keywords: myelofibrosis, ruxolitinib, allogeneic hematopoietic stem cell transplantation.

Received: September 28, 2020

Accepted: December 15, 2020

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Identification of Mutations in IDH1/2, DNMT3A, ASXL1 Genes of Genome Epigenetic Regulation and Their Co-Occurrence with FLT3, NPM1, RUNX1 Mutations in Acute Myeloid Leukemia

AUTOIMMUNE THROMBOCYTOPENIA ,

EV Belotserkovskaya1,2, EK Zaikova1,2, AV Petukhov1,2,3, ON Demidov2, KA Levchuk1, IG Budaeva1, DV Zaitsev1, YuD Rogovaya1, AA Shatilova1, KV Bogdanov1, YuV Mirolyubova1, TS Nikulina1, AYu Zaritskey1, LL Girshova1

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: Ekaterina Vasilevna Belotserkovskaya, PhD in Biology, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; e-mail: belotserkovskaya.ev@gmail.com

For citation: Belotserkovskaya EV, Zaikova EK, Petukhov AV, et al. Identification of Mutations in IDH1/2, DNMT3A, ASXL1 Genes of Genome Epigenetic Regulation and Their Co-Occurrence with FLT3, NPM1, RUNX1 Mutations in Acute Myeloid Leukemia. Clinical oncohematology. 2021;14(1):13–21. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-13-21

ABSTRACT

Aim. To identify mutations in IDH1/IDH2, DNMT3A, and ASXL1 genes responsible for genome epigenetic regulation and their co-occurrence with FLT3, NPM1, and RUNX1 mutations in newly diagnosed adult acute myeloid leukemias (AML).

Materials & Methods. The study included 56 patients with newly diagnosed AML treated at the VA Almazov National Medical Research Center. Among them there were 34 men and и 22 women aged 18–76 years (median 46 years). Mutation status of IDH1, IDH2, DNMT3A, and ASXL1 genes of epigenetic regulation was assessed by Sanger sequencing method. Molecular genetic analysis of FLT3, NPM1, and RUNX1-RUNX1T1 genes was performed using commercial kits.

Results. Mutations in epigenetic regulation genes were detected in 14 (25 %) out of 56 patients. Mutation prevalence was not associated with risk groups (p = 0.072). IDH1/2 mutations were identified in 15.6 % of patients and were significantly oftener observed concurrent with NPM1 mutations (62.5 %; p = 0.01) compared to patients with wild-type IDH1/2. In most patients IDH1/2 mutations were associated with normal karyotype (p = 0.002). DNMT3A (R882) mutation was identified in 4 (7.1 %) out of 56 patients within the analyzed group. In 6 patients (11.1 %) ASXL1 mutations were detected co-occurring with RUNX1-RUNX1T1 and FLT3-ITD mutations.

Conclusion. Mutations in epigenetic regulation genes are often identified in AML patients and can be concurrent with abnormalities in NPM1, FLT3 и RUNX1 genes.

Keywords: acute myeloid leukemias, IDH1, IDH2, DNMT3A, and ASXL1 genes of epigenetic regulation, epigenetic factors.

Received: August 20, 2020

Accepted: December 2, 2020

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Factors for Sustaining Molecular Remission after Discontinuation of Tyrosine Kinase Inhibitors Therapy in Chronic Myeloid Leukemia: Results of Non-Randomized Prospective Clinical Trial

AUTOIMMUNE THROMBOCYTOPENIA ,

OA Shukhov, AN Petrova, EYu Chelysheva, AV Bykova, IS Nemchenko, AG Turkina

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

For correspondence: Oleg Aleksandrovich Shukhov, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-16-36, +7(985)287-12-69; e-mail: shuhov@list.ru

For citation: Shukhov OA, Petrova AN, Chelysheva EYu, et al. Factors for Sustaining Molecular Remission after Discontinuation of Tyrosine Kinase Inhibitors Therapy in Chronic Myeloid Leukemia: Results of Non-Randomized Prospective Clinical Trial. Clinical oncohematology. 2021;14(1):1–12. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-1-12

ABSTRACT

Aim. To study the impact of different clinical and biological factors on sustaining molecular remission after discontinuation of tyrosine kinase inhibitors (TKI) therapy in chronic myeloid leukemia (CML) patients with a stable deep molecular response (MR).

Materials & Methods. The prospective multi-center trial on molecular remission sustainability after TKIs withdrawal, held from 2015 to 2019, enrolled 98 CML patients. The trial included patients with chronic phase CML treated with TKIs at least during 3 years and having a stable deep MR (≤ МО4; BCR-ABL < 0.01 %) during at least 2 years. Molecular monitoring was carried out every month during first 6 months after TKIs withdrawal, every 2 months during 0.5–1 year, and every 3 months after 1-year follow-up. In case of the loss of major MR (BCR-ABL > 0.1 %) therapy was reinitiated.

Results. Three-year molecular relapse-free survival was 51 % (95% confidence interval 41–61 %) in all patients, 25 % in patients with the failure of prior treatment discontinuation, and 53 % in patients who discontinued TKI therapy for the first time. According to univariate analysis, the following factors proved to be significant: persistance of deep MR, duration of therapy, and depth of MR. It was shown that TKI therapy duration, but not deep MR persistance, has independent prognostic value for the Russian population of CML patients. No significant differences were identified in 3-year molecular relapse-free survival in the groups of patients treated only with imatinib (55 %) compared with patients who received 2nd generation TKI (TKI2) as first-line (70 %; p = 0.26) and second-line (39 %; p = 0.09) therapy. However, duration of therapy in patients treated with TKI2 as first-line therapy was more than twice as short as in patients treated with imatinib as first-line therapy (median 41.5 vs. 96.4 months, respectively; p < 0.0001).

Conclusion. Longer therapy duration and MR depth (≤ MО4.5) before TKI withdrawal raise the probability of sustaining off-treatment remission. The study showed that molecular relapse-free survival does not significantly increase with the use of TKI2 as first-line treatment compared to imatinib. Nevertheless, TKI2 as first-line treatment enables to halve the duration of therapy needed to achieve comparable molecular relapse-free survival, as compared with imatinib.

Keywords: chronic myeloid leukemia, tyrosine kinase inhibitors, deep molecular response, off-treatment remission.

Received: July 30, 2020

Accepted: December 1, 2020

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The Improvement of Treatment Outcomes in Multiple Myeloma Patients Non-Eligible for HDCT and Auto-HSCT Using New Approaches to Early Lines of Therapy (Meeting of Expert Panel)

AUTOIMMUNE THROMBOCYTOPENIA

ПРЕДСЕДАТЕЛЬ ЭКСПЕРТНОЙ ГРУППЫ:

Лариса Павловна Менделеева — д-р мед. наук, профессор, заместитель генерального директора по научной работе и инновациям ФГБУ «НМИЦ гематологии» Минздрава России, г. Москва.

ЭКСПЕРТЫ:

Вадим Вадимович Птушкин — д-р мед. наук, профессор кафедры онкологии, гематологии и лучевой терапии РНИМУ им. Н.И. Пирогова Минздрава России, главный внештатный специалист-гематолог ДЗ г. Москвы, заместитель главного врача по гематологии ГКБ им. С.П. Боткина.

Максим Валерьевич Соловьев — канд. мед. наук, заведующий отделением интенсивной высокодозной химиотерапии парапротеинемических гемобластозов ФГБУ «НМИЦ гематологии» Минздрава России, г. Москва.

Сергей Вячеславович Семочкин — д-р мед. наук, профессор кафедры онкологии и гематологии РНИМУ им. Н.И. Пирогова Минздрава России, г. Москва.

Станислав Семенович Бессмельцев — д-р мед. наук, профессор, заместитель директора по научной работе ФГБУ РосНИИГТ ФМБА России, г. Санкт-Петербург.

Камиль Даниялович Капланов — заведующий отделением гематологии ГБУЗ «Волгоградский областной клинический онкологический диспансер», главный гематолог Комитета по здравоохранению администрации Волгоградской области, г. Волгоград.

Андрей Александрович Мацуга — врач-гематолог, главный внештатный гематолог МУ «Управление здравоохранения г. Ростова-на-Дону».

Валентина Захаровна Молоствова — главный внештатный гематолог МЗ ДФО, заместитель главного врача по терапии, Краевая клиническая больница № 1, г. Хабаровск.

Елена Евгеньевна Зинина — главный внештатный специалист гематолог ДЗ Ханты-Мансийского автономного округа Югры, заведующий отделением гематологии Центра клинико-диагностического (гематологии) Ханты-Мансийского автономного округа Югры.

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New Technology Capabilities of Direct Antiglobulin Test

AUTOIMMUNE THROMBOCYTOPENIA

EA Poponina, EV Butina, AV Iovdii, OD Maksimov, GA Zaitseva, IV Paramonov

Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

For citation: Elena Aleksandrovna Poponina, MD, PhD, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(8332)54-51-83; e-mail: senkina.elena@rambler.ru

For correspondence: Poponina EA, Butina EV, Iovdii AV, et al. New Technology Capabilities of Direct Antiglobulin Test. Clinical oncohematology. 2020;13(4):426–9. (In Russ).

DOI: 10.21320/2500-2139-2020-13-4-426-429

ABSTRACT

Background. Direct antiglobulin test (DAT) is used to identify erythrocyte-fixed antibodies and complement components. Gel methods are applied to differentiate immunoglobulin class and subclass in positive DAT, which allows to study the nature of anemia and assess the risk of immune hemolysis.

Aim. To assess the rate of positive DAT in oncohematological patients, to determine class and subclass of erythrocyte-fixed immunoglobulins, and to evaluate their contribution in hemolytic complications.

Materials & Methods. In 393 oncohematological patients at the Kirov Research Institute of Hematology and Transfusiology differentiated DAT was studied using gel test with Bio-Rad (USA) testing sets.

Results. The rate of positive DAT in oncohematological patients varied for different diseases from 6.2 % to 25.2 %, in the total group it was 15.5 %. It accounted for 6.2 % in acute leukemias, 6.3 % in myelodysplastic syndrome, 10 % in chronic myeloid leukemia, 11.9 % in Hodgkin’s lymphoma, 15.4 % in chronic lymphocytic leukemia, 21 % in non- Hodgkin’s lymphoma, and 25.2 % in multiple myeloma. In multiple myeloma, acute leukemia, Hodgkin’s lymphoma, and chronic myeloid leukemia patients the positive test was associated with IgG subclasses 2 and 4. In chronic lymphocytic leukemia and non-Hodgkin’s lymphoma patients IgG1 subclass 1, IgM and C3c, C3d complement components were detected on erythrocyte surfaces. It was shown that IgG2/IgG4 detection was not accompanied by any clinical or laboratory signs of immune hemolysis, IgG1 was responsible for destruction of erythrocytes in 50 % of cases, whereas the detection of C3c, C3d complement components was associated with hemolytic manifestations in 100 % of cases.

Conclusion. Positive DAT should be interpreted in light of laboratory and clinical data. Differentiated test helps to predict hemolytic complications in oncohematological patients.

Keywords: direct antiglobulin test, immunoglobulin class and subclass, immune hemolysis.

Received: April 27, 2020

Accepted: August 20, 2020

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Статистика Plumx английский

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Listeria monocytogenes Meningitis in a Female Patient with Primary Mediastinal (Thymic) Large B-Cell Lymphoma: A Case Report

AUTOIMMUNE THROMBOCYTOPENIA

AM Pronina1, SV Zhuravleva1, GS Yunaev1, IZ Zavodnova1, IA Kurmukov2

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

2 AS Loginov Moscow Clinical Scientific Center, 89 Entuziastov sh., Moscow, Russian Federation, 111123

For correspondence: Ildar Anvarovich Kurmukov, MD, PhD, 89 Entuziastov sh., Moscow, Russian Federation, 111123; e-mail: kurmukovia@gmail.com

For citation: Pronina AM, Zhuravleva SV, Yunaev GS, et al. Listeria monocytogenes Meningitis in a Female Patient with Primary Mediastinal (Thymic) Large B-Cell Lymphoma: A Case Report. Clinical oncohematology. 2020;13(4):420–5. (In Russ).

DOI: 10.21320/2500-2139-2020-13-4-420-425

ABSTRACT

Listeriosis with severe clinical manifestations in the form of bacteraemia, sepsis, and meningitis/meningoencephalitis is a rare but a challenging issue of supportive care in oncohematology. Early diagnosis of listeriosis, as well as any other infection, is hampered by severe general manifestations of a malignant lymphoproliferative disorder or tumor complications and its treatment. In patients with pronounced decreased drug-induced immunity listeriosis is usually characterized as a rapidly developing and, as a rule, severe disease with high immediate mortality. The present article offers a case report of severe listeria infection in a female patient admitted to the intensive care unit for the treatment of primary mediastinal (thymic) large B-cell lymphoma with a large tumor mass in anterior mediastinum complicated by mediastinal and superior vena cava compression syndromes.

Keywords: primary mediastinal (thymic) large B-cell lymphoma, listeriosis, meningitis, supportive care.

Received: June 14, 2020

Accepted: September 17, 2020

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Quality of Life of Hematologists in the Russian Federation According to the RAND SF-36 Questionnaire

AUTOIMMUNE THROMBOCYTOPENIA

NN Tsyba1, TI Ionova2,3, OV Lazareva1, TP Nikitina2,3, NM Porfir’eva3, AN Petrova1, TTs Garmaeva1,4, AG Turkina1

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

2 NI Pirogov Clinic for High Medical Technology, Saint Petersburg State University, 13-15 Kadetskaya line, Saint Petersburg, Russian Federation, 199004

3 Multinational Center for Quality of Life Research, 1 Artilleriiskaya str., Saint Petersburg, Russian Federation, 191014

4 RUDN University, 6 Miklukho-Maklaya str., Moscow, Russian Federation, 117198

For correspondence: Nikolai Nikolaevich Tsyba, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-15-10; e-mail: tsyba2007@yandex.ru; Olga Veniaminovna Lazareva, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: stakhino@gmail.com

For citation: Tsyba NN, Ionova TI, Lazareva OV, et al. Quality of Life of Hematologists in the Russian Federation According to the RAND SF-36 Questionnaire. Clinical oncohematology. 2020;13(4):411–9. (In Russ).

DOI: 10.21320/2500-2139-2020-13-4-411-419

ABSTRACT

Medical profession is notable for its enormous social value and associated with no less responsibility. At the same time, society’s requirements for doctors constantly increase. The regulation of medical activities in various disciplines becomes more and more stringent. The aim of the present article was to study the quality of life of 104 hematologists working in different regions of the Russian Federation. For this purpose, the Russian-language version of RAND SF-36 health survey questionnaire was used. Young doctors aged 35–44 years showed lowest scores on mental health inventory which may indicate negative emotional status and a low level of positive emotions. Compared to relatively healthy respondents, hematologists show a low level of emotional role functioning that may also indicate negative emotional status which in turn negatively affects the quality of health care delivery and appears to be a contributing factor in burnout syndrome. Compared to relatively healthy respondents, hematologists show higher pain scores which may indicate a specific attitude of doctors to pain due to their professional approach. Similar quality of life indicators indirectly suggest that hematologists in different regions of the Russian Federation regard their professional activities as a priority, and it affects their quality of life. Both the results obtained and the literature review prove the relevance of the study of human resources and development of programs aimed at continuity of personnel in the health care system. The quality of life of doctors in different disciplines should become the object of comprehensive sociological, clinical, and sanitation studies which will permit to design a program to improve the quality of life of the medical professionals.

Keywords: quality of life, hematologist, doctors’ quality of life, RAND SF-36 questionnaire.

Received: May 18, 2020

Accepted: September 4, 2020

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Successful Treatment of Aplastic Anemia in the Kyrgyz Republic

AUTOIMMUNE THROMBOCYTOPENIA

SM Mamatov, EM Sadabaev, OA Dzhakypbaev, MO Eralieva

IK Akhunbaev Kyrgyz State Medical Academy, 92 Akhunbaev str., Bishkek, Kyrgyz Republic, 720020

For correspondence: Sagynali Murzaevich Mamatov, 92 Akhunbaev str., Bishkek, Kyrgyz Republic, 720020; Tel.: 996(555)48-00-77; е-mail: s.480077@mail.ru

For citation: Mamatov SM, Sadabaev EM, Dzhakypbaev OA, Eralieva MO. Successful Treatment of Aplastic Anemia in the Kyrgyz Republic. Clinical oncohematology. 2020;13(4):406–10. (In Russ).

DOI: 10.21320/2500-2139-2020-13-4-406-410

ABSTRACT

Aim. To assess the outcomes of combined immunosuppressive therapy in patients with severe aplastic anemia (АА) reflecting the first experience with the use of antithymocyte globulin and cyclosporine A at the National Center of Oncology and Hematology of Kyrgyz Republic Ministry of Health.

Materials & Methods. The trial included 24 AA patients (14 men and 10 women) aged 18–70 years. All patients received combined immunosuppressive therapy at the Hematology Department of the National Center of Oncology and Hematology of Kyrgyz Republic Ministry of Health (Bishkek).

Results. Initially the effect of immunosuppressive therapy was observed in 15 (62.5 %) out of 24 AA patients, 9 (37.5 %) patients did not respond to it. In 12 months after the start of combined immunosuppressive therapy the effect of it was reported in 18 (75 %) patients, 6 (25 %) patients showed no effect. The outcomes of combined immunosuppressive therapy in our study were independent of the age of patients and severity of the disease.

Conclusion. The first experience with the use of combined immunosuppressive therapy in patients with severe AA proved to be highly successful in terms of its efficacy. Immunosuppressive therapy comes first when allogeneic hematopoietic stem cell transplantation from a relative donor is not possible. Combined immunosuppressive therapy started immediately after AA diagnosis gives hope for achieving stable remission and blood components (erythrocytes, thrombocytes) transfusion independence.

Keywords: aplastic anemia, combined immunosuppressive therapy, antithymocyte globulin, cyclosporine A.

Received: May 15, 2020

Accepted: September 3, 2020

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REFERENCES

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Pattern of Immunocompetent Peripheral Blood Cell Subpopulations in B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA

EG Kuzmina, TYu Mushkarina, TV Konstantinova, SV Zatsarenko, SV Shakhtarina, AYu Terekhova, NA Falaleeva, LYu Grivtsova

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

For correspondence: Svetlana Valer’evna Zatsarenko, 4 Koroleva str., Obninsk, Kaluga Region, Russian Federation, 249031; e-mail: vesper04@mail.ru

For citation: Kuzmina EG, Mushkarina TYu, Konstantinova TV, et al. Pattern of Immunocompetent Peripheral Blood Cell Subpopulations in B-Cell Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Clinical oncohematology. 2020;13(4):395–405. (In Russ).

DOI: 10.21320/2500-2139-2020-13-4-395-405

ABSTRACT

Background. In the WHO classification small lymphocytic lymphoma (SLL) and B-cell chronic lymphocytic leukemia (В-CLL) are combined into one nosological entity of lymphoid tumors due to their similar tumor cell immunophenotype. Up to now, there is no consensus on either their similarities or the differences between them. Distinction between В-CLL and SLL is drawn with respect to clinical and hematological manifestations of tumors. The reason for the differences that determine tumor spreading in a patient may lie in specific states of some immune system components. Comparison of immune system parameters within the CLL/SLL model provides a unique opportunity to trace the behavior of immunity indicators in local und disseminated pathogenetically similar neoplastic processes and to identify possible prognostic factors.

Aim. To compare quantitative representations of peripheral blood lymphocyte subpopulations in SLL and В-CLL.

Materials & Methods. Immunocompetent cells (relative and absolute Т- and NK-cell counts), immunophenotype, and tumor clone volume were assessed using multicolor flow cytometry based on the expression of СD3, CD4, CD8, CD16, CD19, CD20, CD23, CD5, CD79b, FMC7, CD22, CD43, CD38 antigens, and immunoglobulins light chain Igκ and Igλ. Before chemotherapy onset, the data of 17 SLL and 81 CLL patients (22 of them with B-lymphocyte count of 35–79 % and 59 with 80–99 %) were compared. As a control, peripheral blood lymphocyte subpopulations in 50 relatively healthy individuals (blood donors) were analyzed.

Results. The analysis of NK-cells and Т-lymphocyte subpopulations in SLL showed the preserved number of killer/cytotoxic cells of innate and adaptive immunity (CD16+, CD8+), the reduction of CD4+ Т-cell count, and CD4/CD8 ratio. In CLL a considerable increase of main subpopulations of residual normal lymphocytes was detected. However, the extent of their increase proved to be considerably lower than increase in the volume of tumor B-cell clone, which signifies a rising exhaustion of immune system effector components.

Conclusion. The present study yielded characteristic features of residual normal lymphocyte subpopulations in SLL and CLL with different leukocytosis grades. SLL patients demonstrated the reduction of relative and absolute Т-cell counts with Т-helper (CD3+, СD4+) phenotype, and the increase of cytotoxic CD8+ Т-cells and NK-cells. Lymphocytosis (35–79 %) in the CLL-I group was due not only to tumor В-cells but also to Т-killer (CD16+, CD8+) and Т-helper (CD4+) absolute counts, which were 1.7–2.5 times higher than in SLL and the control group. Residual lymphocyte subpopulation pattern (80–99 %) in the CLL-II group compared with the control group was characterized by a significantly higher absolute count of CD8+ T-cells and CD16+ NK-cells, as well as higher Т-regulatory index compared with SLL and CLL-I groups. These data point to the necessity for further and more detailed study of residual lymphocyte subpopulation pattern within the CLL/SLL model in order to identify additional predisposing factors.

Keywords: chronic lymphocytic leukemia/small lymphocytic lymphoma, tumor B-cell clone, peripheral blood lymphocyte subpopulations, flow cytometry.

Received: April 22, 2020

Accepted: August 30, 2020

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Clinical and Immunomorphological Characteristics of Lymphomatoid Papulosis Type E (Literature Review and Case Report)

AUTOIMMUNE THROMBOCYTOPENIA ,

TT Valiev1, AM Kovrigina2, TS Belysheva1

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, Kovrigina AM, Belysheva TS. Clinical and Immunomorphological Characteristics of Lymphomatoid Papulosis Type E (Literature Review and Case Report). Clinical oncohematology. 2020;13(4):389–94. (In Russ).

DOI: 10.21320/2500-2139-2020-13-4-389-394

ABSTRACT

Lymphomatoid papulosis (LP) is a rare variant of benign lymphoproliferative disease with skin involvement. Based on clinical, morphological, and immunobiological characteristics, WHO hematopoietic and lymphoid tissue tumor classification (2016) differentiates between several LP types: А, В, С, D, Е, and with 6p25.3 rearrangement. The present article reviews the literature on clinical course, pathomorphological, immunological, and biomolecular characteristics of LP in adults and children. For the first time in the domestic literature, it provides a case report of LP, type E, in a 2-year-old child. Differential diagnosis and optimal disease management of LP are also described in detail.

Keywords: lymphomatoid papulosis, clinical features, diagnosis, treatment.

Received: June 9, 2020

Accepted: September 15, 2020

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