Carmustine in the Therapy of B-Cell Lymphomas

DA Koroleva, EE Zvonkov

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

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

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

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


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

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

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

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

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

Received: July 15, 2021

Accepted: September 10, 2021

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Familial Aggregation in Hodgkin’s Lymphoma

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:

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


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

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:

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


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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Hodgkin’s Lymphoma in HIV-Infected Patients

AV Pivnik1, AM Vukovich2, NV Kremneva1, MG Dubnitskaya1, AV Tsakhilova1

1 AS Loginov Moscow Clinical Scientific Center, 86 Entuziastov sh., Moscow, Russian Federation, 111123

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

For correspondence: Prof. Aleksandr Vasilevich Pivnik, MD, PhD, 86 Entuziastov sh., Moscow, Russian Federation, 111123; Tel.: +7(906)065-99-32; e-mail:

For citation: Pivnik AV, Vukovich AM, Kremneva NV, et al. Hodgkin’s Lymphoma in HIV-Infected Patients. Clinical oncohematology. 2021;14(1):63–8. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-63-68


Aim. To assess clinical and laboratory characteristics of the unique category of HIV-positive patients with hepatitis C or B co-infection combined with Hodgkin’s lymphoma (HL).

Materials & Methods. The paper provides data on 85 HIV-positive patients with HL followed-up at the Department of Hematology and Secondary Immunodeficiencies of the AS Loginov Moscow Clinical Scientific Center from 2002 to 2019 (data on 2008–2010 are not available). The distribution of patients by sex was approximately equal, median age was 35 years (range 20–74 years).

Results. Histological HL variant is predominantly mixed-cell with many positive tests for Epstein-Barr virus. More than 80 % of patients with concomitant HIV infection were admitted to the AS Loginov Center with HL stage III/IV. Most of them received highly active anti-retroviral therapy (HAART) before HL diagnosis. The distinguishing feature of HIV-positive patients with HL appeared to be high (as compared to HIV patients with other lymphoma variants) CD4+ lymphocyte count. This phenomenon is considered within the framework of immune reconstitution inflammatory syndrome (IRIS). A clue to this phenomenon may lay the foundation in addressing the issue of lymphoma genesis and development. Viral load was moderate and undetectable. Hepatitis C and/or B co-infection was identified in 75 % of patients. Antiviral therapy for concomitant hepatitis C was administered concurrent with HAART. All patients received АBVD, BEACOPP-14, BEACOPP-escalated, DHAP, ESHAP antitumor regimens. Radiotherapy was used if necessary. In hepatitis C HAART and direct-acting drugs were administered concurrent with chemotherapy. No severe adverse reactions were observed. Even before starting antitumor treatment of HL patients with concomitant HIV and/or hepatitis viral infections, mortality was 8 %. But in the group of patients with the same co-infections who received HL chemotherapy, mortality was 10 %. The cause of death was HL stage IVB with viral liver cirrhosis, agranulocytosis, and sepsis.

Conclusion. Diseases considered incurable in the past, such as HL and hepatitis C, can be healed today. Compromised immunity of HIV-positive patients can be successfully stabilized with HAART.

Keywords: Hodgkin’s lymphoma, HIV infection, immune reconstitution inflammatory syndrome (IRIS).

Received: April 4, 2020

Accepted: November 9, 2020

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Long-Term Outcomes of Nivolumab Therapy in Patients with Relapsed/Refractory Classic Hodgkin’s Lymphoma after High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Real Clinical Practice

KV Lepik1, NP Volkov1, NB Mikhailova1, EV Kondakova1, LA Tsvetkova1, YuR Zalyalov1, EE Lepik1, LV Fedorova1, AV Beinarovich1, MV Demchenkova2, OG Smykova1, PV Kotselyabina1, IS Moiseev1, VV Baikov1, BV Afanasyev1

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

2 Regional Oncologic Dispensary, 32 Frunze str., Irkutsk, Russian Federation, 664035

For correspondence: Kirill Viktorovich Lepik, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; е-mail:

For citation: Lepik KV, Volkov NP, Mikhailova NB, et al. Long-Term Outcomes of Nivolumab Therapy in Patients with Relapsed/Refractory Classic Hodgkin’s Lymphoma after High-Dose Chemotherapy with Autologous Hematopoietic Stem Cell Transplantation in Real Clinical Practice. Clinical oncohematology. 2020;13(3):280–8 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-280-288


Aim. To assess prognostic factors and to analyze the outcomes of nivolumab therapy in patients with relapsed/refractory classic Hodgkin’s lymphoma (cHL) after autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The retrospective analysis included 42 patients treated with nivolumab 3 mg/kg after auto-HSCT in the period from 2016 to 2020. The response to nivolumab therapy was assessed every three months by whole-body PET/CT based on LYRIC criteria. Toxicity profile was assessed by establishing adverse events (AE) based on NCI CTCAE 4.03 criteria.

Results. The study included 42 patients with relapsed/refractory cHL: 21 (50 %) men and 21 (50 %) women. The median age was 32.5 years (range 22–43 years). At diagnosis the following cHL stages were identified: stage II in 14 pts (33.3 %), stage III in 12 pts (28.6 %), and stage IV in 16 pts (38.1 %). Primary chemoresistance after the first-line therapy was observed in 26 pts (61.9 %) and early relapse in 4 pts (9.52 %). The median follow-up was 38 months, 3-year overall survival was 97 % (95% confidence interval, 95% CI, 83.2–99.6 %), 3-year progression-free survival (PFS) was 34.8 % (95% CI 20.3–49.9 %; median 12.9 months). Objective response was reported in 69 % of patients, complete response (CR) in 33.3 %, partial response in 35.7 %, stable disease in 7.1 %, indeterminate response in 14.3 %, and progression in 9.5 % of patients. The analysis of factors affecting PFS revealed significant differences in patients who reached CR after 6 nivolumab cycles: 3-year PFS 56.2 % (95% CI 24.4–79.1 %) vs. 25.2 % (95% CI 10.46–43.1 %) in patients who did not reach CR (= 0.054). If extranodal lesions were identified at nivolumab therapy onset, PFS was 29 % (95% CI 7.8–37.5 %) vs. 68 % (95% CI 35.9–86.8 %) in their absence (= 0.0079). The overall rate of AEs on nivolumab therapy was 92.9 %, severe AEs of grade 3–4 were observed in 19.1 % of patients.

Conclusion. Nivolumab shows high efficacy in the treatment of patients with relapsed/refractory cHL after the failure of auto-HSCT and considerably improves prognosis compared with historical control. The efficacy of nivolumab is independent of brentuximab vedotin use and duration of prior therapy. Throughout the follow-up period the toxicity level of nivolumab was acceptable and controlled. Clinical factors that affect prognosis for patients on immunotherapy were identified.

Keywords: Hodgkin’s lymphoma, nivolumab, brentuximab vedotin, auto-HSCT, immunotherapy.

Received: March 24, 2020

Accepted: June 15, 2020

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Bendamustine in the Treatment of Relapsed/Refractory Hodgkin’s Lymphoma: Literature Review and Clinical Experience

SS Shklyaev, NA Falaleeva, TI Bogatyreva, AYu Terekhova, MA Danilova

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

For correspondence: Stanislav Sergeevich Shklyaev, MD, PhD, 4 Koroleva str., Kaluga Region, Obninsk, Russian Federation, 249036; Tel.: +7(484)399-30-31; e-mail:

For citation: Shklyaev SS, Falaleeva NA, Bogatyreva TI, et al. Bendamustine in the Treatment of Relapsed/Refractory Hodgkin’s Lymphoma: Literature Review and Clinical Experience. Clinical oncohematology. 2020;13(2):136–49 (In Russ).

DOI: 10.21320/2500-2139-2020-13-2-136-149


Aim. To assess the efficacy of bendamustine combined with dexamethasone in the treatment of relapsed/refractory Hodgkin’s lymphoma (HL).

Materials & Methods. The article provides an updated review of literature as well as the data of prospective observational clinical trial in 47 HL patients (17 men and 30 women aged 20–65 years, median age 36 years) with relapses after standard and high-dose chemotherapy with autologous hematopoietic stem cell transplantation. The therapy regimen included 120 mg/m2 of bendamustine IV on Days 1 and 2 and 20 mg of oral dexamethasone from Day 1 to Day 4. Retreatment was administered 21 days after the start of the previous one. Radiotherapy was applied only to the regions of massive relapsed lesions and bone destructions with pain syndrome.

Results. From April 2011 to September 2017 all 47 patients received 149 bendamustine + dexamethasone therapy regimens with the overall response of 57 % (complete response 27 %, partial response 30 %). Disease progression on therapy was reported in 20 (43 %) patients, its incidence was the highest after the first (n = 8) or the second cycle (n = 4). In the group of 27 patients with overall response 19 (70 %) patients showed new relapses. In these cases the treatment-free period was from 8 to 31 months (median 11 months). The repeated administration of 57 bendamustine + dexamethasone therapy regimens in 12 out of 47 patients achieved clinical effect for 4–36 months (median 6 months). After the first failure of bendamustine-based therapy 13 patients were treated with brentuximab vedotin and nivolumab, the new salvage therapy drugs. With median follow-up of 22 months (range 1–69 months) median overall survival (OS) and time to the next progression were 35 and 10 months, respectively, in all patients. Multivariate analysis showed that OS was unfavorably affected only by B-symptoms on bendamustine + dexamethasone administration (= 0.046), and the time to the next progression was shorter in the presence of B-symptoms (= 0.017) and in histological variant “nodular sclerosis type II” (= 0.006).

Conclusion. Bendamustine + dexamethasone therapy is a relatively low-toxic and effective method of life prolongation in HL patients with chemotherapy-refractory tumors and recurrent relapses, provided no B-symptoms occur by the start of antitumor therapy.

Keywords: Hodgkin’s lymphoma, bendamustine, chemotherapy-refractory disease, relapses.

Received: December 15, 2019

Accepted: March 20, 2020

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Hodgkin’s Lymphoma: Analysis Results of Volgograd Regional Registry

KD Kaplanov1,2, NP Volkov1, TYu Klitochenko1, IV Matveeva1, AL Shipaeva1, MN Shirokova1, NV Davydova3, EG Gemdzhian4

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

2 Volgograd Medical Scientific Center, 1G Rokossovskogo str., Volgograd, Russian Federation, 400081

3 Consultation and Diagnosis Polyclinic No. 2, 114A Angarskaya str., Volgograd, Russian Federation, 400081

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

For correspondence: Kamil Daniyalovich Kaplanov, MD, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail:

For citation: Kaplanov KD, Volkov NP, Klitochenko TYu, et al. Hodgkin’s Lymphoma: Analysis Results of Volgograd Regional Registry. Clinical oncohematology. 2019;12(4):363–76 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-363-376


Background. The present paper discusses feasibility of first- and second-line therapies as well as the significance of different risk factors in the population of all patients with newly diagnosed Hodgkin’s lymphomas (HL) in a 14-year period based on the data of Volgograd regional registry.

Materials & Methods. During the period 2003 to 2017 the population registry of Department of Hematology of Volgograd Regional Clinical Oncology Dispensary included the data of all the patients with newly diagnosed HL (n = 622): 272 (44 %) men and 350 (56 %) women aged 18 to 84 years (mean age 38 years, median age 33 years). There were 97 (16 %) patients with early stages and without risk factors, 165 (27 %) patients with early stages and risk factors, 360 (59 %) patients with advanced stages, 308 (50 %) patients with toxic symptoms (stage B), and 179 (29 %) patients with bulky tumor lesions (≥ 10 cm). ABVD treatment regimen was administered in 190 (30.5 %) patients, increased-dose BEACO(D)PP in 39 (6 %) patients, BEACO(D)PP-14 in 159 (26 %) patients, standard BEACO(D)PP in 200 (32 %) patients, IVDG in 25 (4 %) patients, and other regimens in 9 (1.5 %) patients. The second-line treatment was administered in 120 (19 %) out of 622 patients. By the end of August 2018, the number of followed-up patients was 514 (83 %), 108 (17 %) patients had died. The prognostic value of the International Prognostic Score (IPS), PET, and other factors was assessed by means of Cox’s multivariate regression analysis. Pharmacoeconomic analysis of differences between options of first-line therapy was based on Markov model.

Results. In the group of patients with advanced HL stages treated with escalated BEACO(D)PP (the increased-dose regimen and BEACO(D)PP-14) 5- and 10-year overall survival (OS) was 83 % and 74 %, respectively, OS median was not reached. On standard BEACO(D)PP patients with advanced HL stages had OS median of 139 months (11.6 years) and 5- and 10-year OS of 68 % and 54 %, respectively (= 0,012). In the group of patients with early stages and poor prognosis treated with escalated regimens BEACO(D)PP 5- and 10- year OS was 100 % and 90 %, respectively, in the combined group treated with ABVD and standard BEACO(D)PP it was 83 % and 75 % (= 0.035). Replacement of procarbazine with dacarbazine in the standard and increased-dose BEACOPP regimens did not affect treatment efficacy. Markov analysis demonstrated the advantages of the escalated regimens for treatment of early stages with poor prognosis and advanced stages in terms of life years gained. Out of 7 IPS factors male sex, age ≥ 45 years, hemoglobin < 105 g/L, and albumin < 40 mg/L significantly impacted OS. Based on these data an adjusted prognostic index was suggested.

Conclusion. The advantage of the escalated strategy of first-line therapy in HL is reflected in survival parameters and is based on pharmacoeconomic evidence. The significance of some laboratory IPS risk factors can be reviewed; most obvious is increasing importance of PET for predicting the need for salvage therapy.

Keywords: Hodgkin’s lymphoma, BEACO(D)PP, ABVD, International Prognostic Score, survival analysis, pharmacoeconomics, Markov model, life years gained (LYG), incremental cost-effectiveness ratio (ICER).

Received: February 21, 2019

Accepted: September 17, 2019

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PD-1 Blockade with Nivolumab as a New Immunotherapy for Classical Hodgkin’s Lymphoma

EA Demina

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

For correspondence: Prof. Elena Andreevna Demina, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; e-mail:

For citation: Demina EA. PD-1 Blockade with Nivolumab as a New Immunotherapy for Classical Hodgkin’s Lymphoma. Clinical oncohematology. 2018;11(3):213–19.

DOI: 10.21320/2500-2139-2018-11-3-213-219


During the last two decades individualization of programmed treatment combined with intensified chemotherapy has proven to be effective treatment for the majority of classical Hodgkin’s lymphoma (cHL) patients. However, in 10–30 % of cases relapses and resistance to therapy still occur. Further intensification of therapy induces toxicity that leads to decrease in overall survival and quality of life. The standard second-line treatment with high-dose chemotherapy (HDCT) and autologous hematopoietic stem cell transplantation (auto-HSCT) allows for the achievement of long-term 5-year progression-free survival only in 50–60 % of patients with relapsed disease and not more than 40–45 % of patients with refractory disease. Approximately 50 % of patients relapse after HDCT and auto-HSCT. The median overall survival of relapsed patients does not exceed 2 years. Allogeneic HSCT improves treatment results to some extent, but is not an optimal strategy in all patients. A search for new treatment options has been made to improve effectiveness of relapsed and refractory cHL treatment and to reduce toxicity of highly effective programs. А new CD30-targeted conjugate brentuximab vedotin was developed to use anti-CD30 monoclonal antibodies against a specific marker of tumor Reed-Sternberg cells allowing for the transfer of the highly effective antitumor compound of monomethyl auristatin E directly to tumor cells. This drug showed high effectiveness, although failed to provide a complete solution to the problem. The development of anti-PD1 antibody nivolumab opened up new opportunities for cHL treatment. This paper reviews literature information on pharmacological data and antitumor mechanisms of the drug as well as the results of significant international randomised studies.

Keywords: nivolumab, Hodgkin’s lymphoma, relapse, resistance, treatment.

Received: February 5, 2018

Accepted: April 30, 2018

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Polymerase Chain Reaction for Prognosis Assessment and Monitoring of the Epstein-Barr Virus-Associated Hodgkin’s Lymphoma

MA Katin1, IV Zhil’tsov1, VM Semenov1, DK Novik2

1 Vitebsk State Medical University, 27 Frunze pr-t, Vitebsk, Republic of Belarus, 210023

2 Republican Applied Research Center for Radiation Medicine and Human Ecology, 290 Il’icha str., Gomel, Republic of Belarus, 246040

For correspondence: Prof. Ivan Viktorovich Zhil’tsov, MD, PhD, 27 Frunze pr-t, Vitebsk, Republic of Belarus, 210023; Tel.: +375(29)7104368-93-29; e-mail:

For citation: Katin NA, Zhil’tsov IV, Semenov VM, Novik DK. Polymerase Chain Reaction for Prognosis Assessment and Monitoring of the Epstein-Barr Virus-Associated Hodgkin’s Lymphoma. Clinical oncohematology. 2018;11(2):182–6.

DOI: 10.21320/2500-2139-2018-11-2-182-186


The review provides the analysis of 34 papers on polymerase chain reaction (PCR) as a method of the Epstein-Barr virus (EBV) DNA detection in biological material of patients with EBV-associated cancer diseases including Hodgkin’s lymphoma (HL). A comparative analysis of different methods of EBV DNA detection in biological material is presented. EBV is associated with HL in 20 to 100 % of cases depending on a geographic region and HIV status. EBV-associated HLs are characterized by latency type II. EBV is found in all the atypical cells and can be detected in blood of EBV-associated HL patients by means of the PCR method. The review includes the results of studies on EBV detection using the PCR method compared to in situ methods of hybridization and immunohistochemistry in various EBV-associated cancer diseases including HL. The obtained data indicate that PCR can be used for quantitative determination of EBV DNA in blood plasma of HL patients for therapeutic efficacy monitoring and prognosis assessment of disease and relapses. Quantitative determination of EBV DNA in blood plasma of HL patients using the real time PCR method is a promising technique. Its further practical application requires standardization of the method, larger trials, and comparison to positron emission tomography.

Keywords: Epstein-Barr virus, Hodgkin’s lymphoma, polymerase chain reaction.

Received: December 20, 2017

Accepted: February 28, 2018

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Conventional and Conformal Radiotherapy with and without Beam Intensity Modulation in Patients with Stage II Hodgkin’s Lymphoma with Supradiaphragmal Lesions

YuN Vinogradova1, EI Ivanova1, AI Chumachenko1, EV Smirnova2, GI Andreev2, AM Kalesnik2, NA Vorob’ev2, NV Il’in1

1 AM Granov Russian Research Centre of Radiology and Surgery Technologies, 70 Leningradskaya str., Pesochnyi, Saint Petersburg, Russian Federation, 197758

2 Nuclear Medicine Centre of SM Berezin International Institute of Biological Systems, 43 Karl Marx str., Pesochnyi, Saint Petersburg, Russian Federation, 197758

For correspondence: Nikolai Vasil’evich Il’in, PhD, Professor, 70 Leningradskaya str., Pesochnyi, Saint Petersburg, Russian Federation, 197758; Tel.: +7(812)596-90-35; e-mail:

For citation: Vinogradova YuN, Ivanova EI, Chumachenko AI, et al. Conventional and Conformal Radiotherapy with and without Beam Intensity Modulation in Patients with Stage II Hodgkin’s Lymphoma with Supradiaphragmal Lesions. Clinical oncohematology. 2018;11(1):70-7.

DOI: 10.21320/2500-2139-2018-11-1-70-77


Aim. To increase the efficacy of chemo-radiotherapy in patients with stage II Hodgkin’s lymphoma (HL) with supradiaphragmal lesions by different fractionation (conventional fractionation [CF] and multi-fractionation [MF]) and various radiation volume (mantle radiotherapy, involved field radiotherapy [IFRT] or involved site radiotherapy [ISRT]).

Materials & Methods. The clinical trial included 317 patients with stage II classical HL with supradiaphragmal lesions who have received chemo-radiotherapy in AM Granov Russian Scientific Centre of Radiology and Surgery Technologies from 1986 to 2015 (n = 301) and in SM Berezin International Institute of Biological Systems from 2014 to 2016 (n = 16). The mean age was 30.9 years (range 18–65); the study group included 107 men and 210 women. The diagnosis in all the cases was confirmed by immunomorphologic analysis. The treatment program included 2 to 6 cycles of ABVD regimen followed by CF (n = 153) or MF (n = 148) radiation therapy. The patients received mantle radiotherapy or IFRT with the cumulative dose of 30 to 40 Gy (2D planning, 237 patients) or ISRT with the cumulative dose of 30 to 40 Gy (3D planning, n = 80, CF only). The MF-regimen was administered only with 2D planning, mantle radiotherapy and IFRT. The CF-regimen was administered with 2D-planning (n = 89) with the same volume of radiation and 3D planning using conformal RT (3D-CRT) as ISRT with the cumulative dose of 30 to 36 Gy (n = 80). From the total of 80 patients 16 patients were treated with beam intensity modulation (IMRT) and 64 patients were treated without IMRT.

Results. The treatment response (both complete and partial remission) was reported in 235 (99.2 %) of 237 patients of 2D planning group. In 2 cases (0.8 %) a progression of disease was diagnosed. Out of 235 patients with remission 222 (94.5 %) had a complete remission and 13 (5.5 %) had a partial remission. Within the group treated with the conventional RT 19 (8.1 %) patients had recurrent disease. Overall 5- and 10-year survival (OS) was equal and accounted for 98.0 ± 1.4 %, the disease-free survival (DFS) was also equal between groups and accounted for 85.9 ± 1.3 %. The rate of 5- and 10-year OS in patients who received CF was 97.8 ± 1.7 %; the DFS rate for the same period was 85.0 ± 1.5 % with standard fractionation and 86.2 ± 1.6 % with MF (> 0.1). The total number of local radiation reactions and the number of radiation pulmonitis were significantly smaller with the exposure twice daily compared to CF at 2D planning and mantle irradiation. Decreasing the radiation volume from the mantle type to IFRT was shown to reduce the incidence of pulmonitis. The incidence of esophagitis remained the same with different fractionation and the irradiation volumes specified above. The results of the analysis proved the total absence of radiation pericarditis with both types of conformal RT with or without IMRT. No pulmonitis cases were observed with IMRT; the use of 3D-CRT and 2D-RT significantly increased the incidence of pulmonitis. The incidence of esophagitis within the CRT-group (n = 80) was 2 times lower compared to the conventional RT (22.5 % and 43.9 %; < 0.01).

Conclusion. The innovative technologies of radiation therapy allowed to reduce the incidence of early local radiation reactions. These technologies will be the basis for preventing severe late radiation complications that reduce the life expectancy and quality of life of patients with HL.

Keywords: Hodgkin’s lymphoma, radiotherapy, fractionation, 2D and 3D planning.

Received: September 16, 2017

Accepted: December 5, 2017

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