Herpes Virus Reactivation in Lymphoma Patients During and After Autologous Hematopoietic Stem Cell Transplantation

YaK Mangasarova, YuO Davydova, DS Tikhomirov, OV Margolin, LG Gorenkova, ES Nesterova, FE Babaeva, AE Misyurina, MO Bagova, EA Fastova, AU Magomedova, IV Galtseva, TA Tupoleva, SK Kravchenko

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

For correspondence: Yana Konstantinovna Mangasarova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(926)395-82-52; e-mail: v.k.jana@mail.ru

For citation: Mangasarova YaK, Davydova YuO, Tikhomirov DS, et al. Herpes Virus Reactivation in Lymphoma Patients During and After Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2022;15(3):289–97. (In Russ).

DOI: 10.21320/2500-2139-2022-15-3-289-297


ABSTRACT

Aim. To assess the detection rate of human herpes virus DNA (of cytomegalovirus, herpes simplex virus types 1 and 2 [HSV-1/2], human herpes virus type 6 [HHV-6], and Epstein-Barr virus) in different biological environments at different stages of autologous hematopoietic stem cell transplantation (auto-HSCT) as well as the effect of immune factors on reactivation of viruses under study.

Materials & Methods. From 2019 to 2021 the study enrolled 87 lymphoma patients during and after auto-HSCT. Virological monitoring was performed on biological fluids (blood, saliva, urine, etc.) on therapeutic grounds prior to conditioning regimen on Day 0 as well as on Day +5 and Day +10 after auto-HSCT. On these days (Day 0, Day +5, and Day +10) the immune factors (IgM, IgG, and IgA levels and pattern of lymphocyte subpopulation in peripheral blood) in 15 % (14/87) of patients were assessed in terms of their effect on herpes virus reactivation.

Results. The overall rate of viral DNA detection increased from 26 % (26/87) to 42 % (37/87) of cases in the period of granulocytopoietic recovery. The most frequent were HHV-6 and HSV-1/2 reactivations reported in 23 % (20/87) and 16 % (14/87) of cases, respectively. The median B-lymphocyte proportion in peripheral blood of patients with herpes virus reactivation was 0.26 %, whereas in patients without reactivation it was 6.7 % (= 0.019). The median absolute B-lymphocyte count in the cohort of patients with detected viral DNAs was 0.001 × 109/L, whereas in patients without them it was 0.098 × 109/L (= 0.026).

Conclusion. A high rate of herpes virus DNA detection in lymphoma patients after auto-HSCT affected neither transplant engraftment nor transplantation mortality. Immune predictors of virus infection reactivation were the decreasing proportion of B-cells in the total lymphocyte count and the absolute B-lymphocyte count in the peripheral blood prior to auto-HSCT.

Keywords: herpes virus infections, transplantation, lymphoma, lymphocyte subpopulation.

Received: January 25, 2022

Accepted: May 15, 2022

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Статистика Plumx английский

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Clinical and Prognostic Value of Molecular Markers of Diffuse Large B-Cell Lymphoma

SM Rastorguev1, DA Koroleva2, ES Boulygina1, SV Tsygankova1, NG Goncharov1, OS Naraikin1, NG Gabeeva2, EE Zvonkov2, AV Nedoluzhko1

1 National Research Center “Kurchatov Institute”, 1 Akademika Kurchatova sq., Moscow, Russian Federation, 123182

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

For correspondence: Artem Valer’evich Nedoluzhko, PhD in Biology, 1 Akademika Kurchatova sq., Moscow, Russian Federation, 123182; Tel.: +7(916)670-55-95; e-mail: nedoluzhko@gmail.com

For citation: Rastorguev SM, Koroleva DA, Bulygina ES, et al. Clinical and Prognostic Value of Molecular Markers of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019:12(1):95–100.

DOI: 10.21320/2500-2139-2019-12-1-95-100


ABSTRACT

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid tumor in adults which is associated with approximately 30–40 % of all non-Hodgkin’s lymphomas. Diagnostic criteria include diffuse growth of large anaplastic tumor cells, expression of В-cell markers, and a high proliferative index. Due to the development of molecular genetic technologies it became obvious that underlying cause of clinical diversity is a huge amount of genetic failures which determine epigenetic modification of gene expression, activation variability of certain signaling pathways, and immunological properties of tumor cells. The study and systemization of molecular markers present a significant trend in DLBCL diagnosis and treatment. This review discusses most important molecular markers and current view on their clinical value.

Keywords: lymphoma, DLBCL, B-cells, transcriptomics, gene expression, epigenomics, genomics.

Received: July 3, 2018

Accepted: December 10, 2018

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Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT

VA Balashova, VI Rugal’, SS Bessmel’tsev, SV Gritsaev, NYu Semenova, SV Voloshin, ZhV Chubukina, AV Shmidt, AD Garifullin, IM Zapreeva, AA Kuzyaeva, II Kostroma, AYu Kuvshinov, AV Chechetkin

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

For correspondence: Valentina Andreevna Balashova, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-19-37; e-mail: vbspb37@mail.ru

For citation: Balashova VA, Rugal’ VI, Bessmel’tsev SS, et al. Correlation of CD34+ Hematopoietic Stem Cells and CFU in Peripheral Blood Apheresis Products in Patients with Malignant Lymphoproliferative Diseases Before and After Cryopreservation Prior to auto-HSCT. Clinical oncohematology. 2018;11(4):368–77.

DOI: 10.21320/2500-2139-2018-11-4-368-377


ABSTRACT

Aim. To establish correlation between CD34+ autologous hematopoietic stem cell (HSC) count and colony-forming units (CFU) in the same peripheral blood apheresis product samples before and after cryopreservation in multiple myeloma and lymphoma patients, and to assess clinical value of these parameters.

Materials & Methods. Cell samples of peripheral blood cytapheresis product and cell cultures were studied before and after cryopreservation in 32 multiple myeloma and 25 lymphoma patients who underwent autologous HSC transplantation. The material was analyzed using culture technique and flow cytometry.

Results. The paper provides information on the relationship between CD34+ HSC count obtained by flow cytometry, and CFU in cell culture obtained by cytapheresis of the same peripheral blood samples. A direct correlation was confirmed between CD34+ count and all the CFUs before and after cryopreservation in lymphoma patients. Correlation between CD34+ count and granulocyte-macrophage CFUs was revealed in multiple myeloma and lymphoma patients before cryopreservation.

Conclusion. The parameter of colony-forming capacity used for the assessment of the functional HSC was shown to be equally reliable criterion for condition evaluation of autotransplant proliferative pool than CD34+ cells. Both methods should be applied for qualitative and quantitative evaluation of an autotransplant for multiple myeloma and lymphoma patients.

Keywords: CD34+ cells, CFU, CFU-GM, correlation, lymphoma, multiple myeloma, apheresis, auto-HSCT.

Received: April 11, 2018

Accepted: July 28, 2018

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Clinical Significance of the PRAME Gene Expression in Oncohematological Diseases

VA Misyurin

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

For correspondence: Vsevolod Andreevich Misyurin, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

For citation: Misyurin AV. Clinical Significance of the PRAME Gene Expression in Oncohematological Diseases. Clinical oncohematology. 2018;11(1):26–33.

DOI: 10.21320/2500-2139-2018-11-1-26-33


ABSTRACT

Although the PRAME activity was first discovered in solid tumors, this gene is very frequently expressed in oncohematological diseases. PRAME can be regarded as a reliable biomarker of tumor cells. Determination of PRAME transcripts is used in residual disease monitoring and molecular relapse diagnostics. Experimentation with PRAME expressing lines of leukemia cells yielded controversial results. Therefore, it is hardly possible to estimate the prognostic value of PRAME activity in oncohematological diseases. In chronic myeloproliferative disease and chronic myeloid leukemia, however, PRAME activity proves to be a predictor of negative prognosis, and on the contrary, it can be regarded as a positive prognostic factor in acute myeloid or lymphoid leukemia. Despite many clinical studies prognostic value of PRAME expression in some diseases requires further investigation. The present literature review contains the data concerning PRAME expression in oncohematological diseases.

Keywords: PRAME, leukemia, lymphoma, prognosis.

Received: September 14, 2017

Accepted: December 2, 2017

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Application of Modern Genome Technologies in Treatment of Lymphomas

MV Nemtsova1, MV Maiorova2

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

2 PA Hertzen Moscow Oncology Research Institute, 3 2-y Botkinskii pr-d, Moscow, Russian Federation, 125284

For correspondence: Marina Vyacheslavovna Nemtsova, DSci, Professor, 2/1 Barrikadnaya str., Moscow, Russian Federation, 125993; Tel: +7(499)252-21-04; e-mail: nemtsova_m_v@mail.ru

For citation: Nemtsova MV, Maiorova MV. Application of Modern Genome Technologies in Treatment of Lymphomas. Clinical oncohematology. 2016;9(3):265-70 (In Russ).

DOI: 10.21320/2500-2139-2016-9-3-265-270


ABSTRACT

Modern achievements in genomics and cancer biology have provided an unprecedented body of knowledge regarding the molecular pathogenesis of lymphoma. Genome-wide association studies and modern computer technologies demonstrated that various histological and immunomorphological subtypes of lymphomas differ at the molecular level, and result from various oncogenic mechanisms. It is clear that the variability of clinical symptoms presented by patients with lymphomas is based on the heterogeneity of tumor cells and features of the molecular pathogenesis. Based on data obtained, strategies for the development of new drugs for treatment of lymphoma have been proposed, including identification of the molecular pathogenesis, assessment of the significance of each stage for the development of tumors and synthesis of a drug with a targeted effect. As a result, several new classes of molecular targeted agents for treatment of lymphomas have been proposed and are being tested in clinical trials. In the modern era of personalized medicine, correct targeted therapy for each type of lymphoma characterized by a unique molecular mechanism of tumor formation is a major challenge in lymphoma treatment.


Keywords: lymphoma, genes expression profile, microRNA, signaling pathways, NF-kB.

Received: February 13, 2016

Accepted: March 14, 2016

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Video-Assisted Thoracoscopic Surgery in Diagnosing Lymphomas

IG Komarov1,2, SYu Sletina1, MI Komarov2, АА Sukhov1

1 N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 Russian Medical Academy of Postgraduate Education, 23 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Igor’ Gennad’evich Komarov, DSci, Professor, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-12-70; e-mail: komarovig@mail.ru

For citation: Komarov IG, Sletina SYu, Komarov MI, Sukhov AA. Video-Assisted Thoracoscopic Surgery in Diagnosing Lymphomas. Clinical oncohematology. 2016;9(1):30–41 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-30-41


ABSTRACT

This article continues a series of papers dwelling on endo-surgery techniques in diagnosing lymphomas. It describes the history of the thoracoscopic surgery and its potential and current use when malignant lymphoproliferative diseases with involvement of chest organs and tissues. It provides brief description of basic instruments, equipment and technique of surgical interventions via the thoracic access. It lists indications and contraindications for the thoracoscopic surgery. In addition, the paper presents analysis of video-assisted thoracoscopic surgeries in 178 patients with suspected malignant lymphoproliferative diseases. During these surgeries, samples for further morphological assessment were obtained from all patients. Lymphomas were confirmed in 120 patients. The article contains two case reports on the video-assisted thoracoscopic interventions performed.


Keywords: lymphoma, diagnostics, video-assisted surgery, thoracoscopy.

Received: November 6, 2015

Accepted: December 24, 2015

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Secondary Hemophagocytic Syndrome in the Adult Patients. Literature Review and Authors’ Experience

VG Potapenko1,2, NA Potikhonova4, VV Baikov2, MB Belogurova1, IA Lisukov3, AV Klimovich1, SV Lapin2, MO Ivanova2, VM Kravtsova2, EI Podol’tseva1, NV Medvedeva1, BV Afanas’ev2

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

2 R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 12 Rentgena str., Saint Petersburg, Russian Federation, 197022

3 I.I. Mechnikov North-Western State Medical University, 41 Kirochnaya str., Saint Petersburg, Russian Federation, 197022

4 Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Vsevolod Gennad’evich Potapenko, Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(812)230-19-33; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko V.G., Potikhonova N.A., Baikov V.V., Belogurova M.B., Lisukov I.A., Klimovich A.V., Lapin S.V., Ivanova M.O., Kravtsova V.M., Podol’tseva E.I., Medvedeva N.V., Afanas’ev B.V. Secondary Hemophagocytic Syndrome in the Adult Patients. Literature Review and Authors’ Experience. Klin. Onkogematol. 2015;8(2):169–84. (In Russ.).


ABSTRACT

Background & Aims. The hemophagocytic syndrome is a dangerous hyperinflammatory syndrome usually caused by an infection. It is a result of excessive cell activation in the mononuclear phagocyte system which is manifested itself through cytopenia, systemic inflammatory reaction, liver and spleen impairment. Since the disease is rare and its diagnosing is very complicated, this syndrome has not been studied thoroughly and is overlooked very often. The aim of this work is to describe authors’ experience in dealing with the secondary hemophagocytic syndrome (HPS) and to present a literature review.

Methods. Clinical and laboratory data of 15 patients aged 16 to 64 (median age 48 years) with secondary HPS observed over the period from 2009 till 2013 were analyzed. Secondary HPS was diagnosed in patients with malignant lymphoproliferative and infectious diseases. HPS signs were found in lymphoproliferative disorders (n = 5), chronic active EBV-infection (n = 3), allogeneic hematopoietic stem cell transplantation (n = 3), acute leukemia (n = 1), multiple myeloma (n = 1), pneumonia (n = 1), and glomerulonephritis (n = 1). 8 patients underwent treatment for HPS: etoposide (n = 1), glucocorticoids (n = 1), intravenous immunoglobulin (n = 2), combination of rituximab + glucocorticoids (n = 2), etoposide + cyclosporine A (n = 1), as well as combined HLH-2004 chemotherapy (n = 1). The median observation period was 42 months.

Results. Among 15 adult patients enrolled into the retrospective analysis, malignant lymphoproliferative disorders and chronic EBV-infection were most common underlying disorders in case of secondary HPS. Early diagnosing is very complicated, because diagnostic criteria accepted at present are typical for the late-phase HPS. The above factors require development of more sensitive and universal diagnostic criteria.

Conclusion. In oncohematological practice, the secondary HPS is a severe complication requiring differential diagnosing with other critical conditions and intensive care. In case of HPS associated with oncohematological disorders, patients require close monitoring throughout the antitumor treatment period and after it.


Keywords: secondary hemophagocytic syndrome, lymphoma, Epstein-Barr virus, etoposide, hematopoietic stem cells transplantation.

Received: December 9, 2014

Accepted: February 7, 2015

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Modern Aspects of Diagnosis and Treatment of Complicated Forms of Non-Hodgkin’s Lymphomas of Small and Large Intestine

OA Malikhova, AO Tumanyan, VA Shalenkov, AG Malikhov, YuP Kuvshinov, GV Ungiadze

N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Ol’ga Aleksandrovna Malikhova, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-43-27; e-mail: malikhova@inbox.ru

For citation: Malikhova OA, Tumanyan AO, Shalenkov VA, et al. Modern Aspects of Diagnosis and Treatment of Complicated Forms of Non-Hodgkin’s Lymphomas of Small and Large Intestine. Clinical oncohematology. 2015;8(2):129–35 (In Russ).


ABSTRACT

Background & Aims. Lymphomas constitute 5 to 10 % of gastrointestinal tumors and most of them are non-Hodgkin’s lymphomas (NHLs). They constitute 30–45 % of all extranodal NHLs. Primary involvement of the gastrointestinal tract is observed in 2/3 of patients. The objective of this study is to determine clinical and morphological features and treatment outcomes of complicated forms of NHLs of the small and large intestine.

Methods. NHLs of the small and large intestine were studied in 189 patients treated in the N.N. Blokhin Russian Cancer Research Center within the period of 1985–2010. Large intestine involvement was observed in 64 patients and small intestine involvement in 125 patients.

Results. Surgical interventions for ileus, bleeding or perforation of a hollow organ were performed in 92 patients with primary or secondary involvement of the small and large intestine (48.7 %). The intestine involvement was primary in 58.9 % of cases and secondary in 41.0 % of cases.

Conclusion. Complications of gastrointestinal NHLs deteriorate the overall survival rate. Patients with small or large intestine involvement require a special approach to diagnosis and treatment because of a high risk of surgical complications.


Keywords: lymphoma, small intestine, large intestine, oncohematology, non-Hodgkin’s lymphomas.

Received: January 30, 2014

Accepted: February 12, 2015

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Positron Emission Tomography in Modern Management of Lymphomas

IP Aslanidi, OV Mukhortova, TA Katunina, IV Ekaeva, MG Shavman

A.N. Bakulev Scientific Center of Cardiovascular Surgery, 135 Rublevskoe sh., Moscow, Russian Federation, 121552

For correspondence: Ol’ga Valentinovna Mukhortova, DSci, 135 Rublevskoe sh., Moscow, Russian Federation, 121552; Tel.: +7(495)414-77-31; e-mail: olgamukhortova@yandex.ru

For citation: Aslanidi IP, Mukhortova OV, Katunina TA, et al. Positron Emission Tomography in Modern Management of Lymphomas. Clinical oncohematology. 2015;8(1):13–25 (In Russ).


ABSTRACT

Objective. The objective is to determine areas of effective application of positron emission tomography (PET) with fluorodeoxyglucose labeled with 18-fluorine (18F-FDG) in patients with lymphomas.

Methods. 56 scientific papers published in 2005–2014 were examined. They analyzed results of recent large studies of PET in patients with lymphomas.

Results. 18F-FDG PET has become an essential part of a diagnostic algorithm for patients with lymphomas which are characterized by active accumulation of 18F-FDG. High precision of PET in patients with some types of lymphomas permit to use this method effectively in clinical practice for staging of the disease, assessment of the treatment efficacy, more precise diagnosis of the relapse prevalence, assessment of results of the anti-relapse therapy, as well as in case of suspected lymphoma transformation. The use of PET at other stages of treatment of lymphoma patients is still pending further scientific research. In case of indolent lymphomas with known low glycolytic activity or lymphomas of rare histological types, PET is used for assessment of the treatment efficacy only if baseline study results (before initiation of treatment) are available. The Deauville five-score scale criteria should be used for assessment of the treatment efficacy. Timely examination during antitumor treatment permits to increase the precision of the PET diagnosing significantly. Solitary foci found by PET are crucial for the choice of treatment and they should be verified by other diagnostic techniques. It is considered unreasonable to use PET for follow-up observation over patients in remission.

Conclusions. PET is a gold standard for staging and assessing the treatment efficacy of lymphomas characterized by active accumulation of 18F-FDG.


Keywords: PET, lymphoma, international guidelines, Deauville five-score scale.

Received: November 14, 2014

Accepted: November 18, 2014

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Video-Assisted Laparoscopic Surgeries in Lymphomas Diagnostics

I.G. Komarov1,2, S.S. Stepanenkova3, M.I. Komarov2

1 Surgical Unit No. 2, N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 Subdepartment of Oncology, Russian Medical Academy of Postgraduate Education, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

3 Subdepartment of Oncology, A.I. Evdokimov Moscow State University of Medicine and Dentistry, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: I.G. Komarov, DSci, Professor, N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-12-70; e-mail: komarovig@mail.ru

For citation: Komarov I.G., Stepanenkova S.S., Komarov M.I. Video-Assisted Laparoscopic Surgeries in Lymphomas Diagnostics. Klin. Onkogematol. 2014; 7(4): 540–550 (In Russ.).


ABSTRACT

The article describes application of modern minimally invasive surgical technologies in oncohematology. The history of the video-assisted surgery is presented. Modern opportunities of the video-assisted laparoscopic surgery in diagnosing of malignant lymphoproliferative disorders were described. The main tools and the equipment, stages of intervention and technique used in video-assisted surgery are briefly described. Indications and contraindications for laparoscopic interventions are presented.


Keywords: lymphoma, diagnosis, video-assisted surgery, laparoscopy.

Accepted: September 17, 2014

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