Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas

In memory of Academician A.I. Vorob’ev,
Russian Academy of Medical Sciences and Russian Academy of Sciences

KA Sychevskaya, SK Kravchenko, FE Babaeva, AE Misyurina, AM Kremenetskaya, AI Vorob’ev

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

For correspondence: Kseniya Andreevna Sychevskaya, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(910)409-79-44; e-mail:

For citation: Sychevskaya KA, Kravchenko SK, Babaeva FE, et al. Stable Chronology of Granulopoiesis under R(G)-DHAP Immunochemotherapy-Induced Cytotoxic Stress in Non-Hodgkin’s Lymphomas. Clinical oncohematology. 2021;14(2):204–19. (In Russ).

DOI: 10.21320/2500-2139-2021-14-2-204-219


Background. Chronology of granulopoiesis based on periodic hematopoiesis model has been thoroughly studied. However, the pattern of influence of chemotherapy- and immunotherapy-induced cytotoxic stress on the development rhythm of a stem cell requires further investigation. The interaction of antitumor drugs with normal hematopoietic cells is relevant for assessing the intensity of chemotherapy adverse events. Besides, there is a demand for studying hematopoiesis under cytotoxic stress to predict immunological reactivity as a condition for efficacy of immunotherapeutic agents, the effect of which is based on cell immunity.

Aim. To study the chronological pattern of leukocyte count dynamics after R(G)-DHAP immunochemotherapy in non-Hodgkin’s lymphomas.

Materials & Methods. The dynamics of leukocyte count changes after R(G)-DHAP immunochemotherapy was analyzed using the data of 39 treatment courses in 19 non-Hodgkin’s lymphomas patients. After 18 out of 39 cycles of treatment granulocyte colony-stimulating factor (G-CSF) was administered to prevent granulocytopenia, in other cases the previously planned hematopoietic stem cell mobilization was performed according to the accepted protocol.

Results. Time to activation of spontaneous granulopoiesis depends neither on G-CSF stimulation, nor on the total dose of growth-stimulating factor and corresponds on average to Day 10 or Day 11 of the break from the last day of immunochemotherapy. The tendency of shorter agranulocytosis duration on prophylactic use of G-CSF is associated with transient hyperleukocytosis at an early stage after completing immunochemotherapy. Regimens with platinum-based drugs, like R(G)-DHAP, are suggested to be combined with immunochemotherapeutic agents in patients with the failure of first-line chemotherapy. The time interval preceding myelopoiesis activation within the first days of the break between the courses is likely to contribute to the initiation of treatment with immunotherapeutic drugs after second-line chemotherapy.

Conclusion. The determination of granulopoiesis dynamics under R(G)-DHAP immunochemotherapy-induced cytotoxic stress enables to plan the optimum G-CSF regimen and to predict the optimum timing of immune antitumor effect combined with chemotherapy.

Keywords: periodic hematopoiesis, mathematical hematopoiesis model, non-Hodgkin’s lymphomas, chemotherapy, immunotherapy, G-CSF, antitumor immunity, R(G)-DHAP.

Received: November 15, 2020

Accepted: February 25, 2021

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Статистика Plumx английский


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Treatment of Aggressive Non-Hodgkin’s Lymphomas in Pregnancy

YaK Mangasarova1, AU Magomedova1, ES Nesterova1, LG Gorenkova1, FE Babaeva1, RG Shmakov2, SK Kravchenko1

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

2 VI Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, 4 Akademika Oparina str., Moscow, Russian Federation, 117997

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

For citation: Mangasarova YaK, Magomedova AU, Nesterova ES, et al. Treatment of Aggressive Non-Hodgkin’s Lymphomas in Pregnancy. Clinical oncohematology. 2020;13(3):316–21 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-316-321


Background. The management of aggressive lymphomas in pregnancy depends on the time of diagnosis and immunomorphological variant of tumor. The rarity of aggressive lymphomas in pregnant women, the absence of consistent approaches to the treatment of such patients, the lack of data on physical growth of children as well as the incidence of newborns’ congenital and acquired pathology make this subject of vital importance.

Aim. To analyze the treatment results in patients with newly diagnosed aggressive lymphoma at different stages of pregnancy.

Materials & Methods. From 1993 to 2020 at the National Research Center for Hematology 74 pregnant women with lymphomas were treated. Aggressive tumors were detected in 17 (23 %) of them: primary mediastinal (thymic) large B-cell lymphoma (n = 14), anaplastic large-cell lymphoma ALK+ (n = 1), high-grade B-cell lymphoma, unspecified (n = 1), and diffuse large B-cell lymphoma (n = 1). The median age of patients was 30 years (range 21–37 years). The median pregnancy stage on the diagnosis of aggressive lymphoma was 21 weeks (range 11–32 weeks).

Results. In 1 case on the diagnosis of aggressive lymphoma at 11 weeks gestation dexamethasone 8 mg daily was administered up to the second trimester of pregnancy, afterwards the patient received polychemotherapy. On the diagnosis of aggressive lymphoma in the second (n = 13) and third (n = 2) trimesters of pregnancy the patients received polychemotherapy followed by delivery. In the third trimester of pregnancy delivery was performed with subsequent polychemotherapy in 1 patient. There were born 18 babies (1 pregnancy was multifetal): 8 girls and 10 boys.

Conclusion. As a result of the chosen tactics and the work of interdisciplinary team of doctors all patients, who completed the treatment, are followed-up in complete remission. All born babies, despite chemotherapy and perinatal complications, are alive and develop without abnormalities.

Keywords: malignant lymphoproliferative disorders, chemotherapy, primary mediastinal (thymic) large B-cell lymphoma, pregnancy.

Received: April 1, 2020

Accepted: June 22, 2020

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Role of Biochemical Inflammatory Markers in Patients with Chemotherapy-Induced Neutropenia

YuN Dubinina1, VO Sarzhevskii2, VYa Melnichenko2

1 Oncology and Hematology Outpatient Clinic, 2 bld. 1 Molodogvardeiskaya str., Moscow, Russian Federation, 121467

2 NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

For correspondence: Yuliya Nikolaevna Dubinina, 2 bld. 1 Molodogvardeiskaya str., Moscow, Russian Federation, 121467; Tel.: +7(499)112-25-04; e-mail:

For citation: Dubinina YuN, Sarzhevskii VO, Melnichenko VYa. Role of Biochemical Inflammatory Markers in Patients with Chemotherapy-Induced Neutropenia. Clinical oncohematology. 2019;12(4):461–7 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-461-467


The growing number of autologous and allogeneic transplantations of bone marrow and hematopoietic stem cells as well as their technological effectiveness give rise to drug antineoplastic therapies with increased toxicity leading to development of complications. The most serious among this sort of complications are infections. Probability of infections in patients with chemotherapy-induced neutropenia reaches 90 %. In this context the search for an optimal marker of infectious complications becomes more and more important. The present review deals with basic biochemical inflammatory markers and the analysis of trials assessing diagnostic and prognostic value of C-reactive protein, procalcitonin, and presepsin.

Keywords: sepsis, autologous bone marrow transplantation, allogeneic bone marrow transplantation, chemotherapy, infection, procalcitonin, presepsin, C-reactive protein.

Received: May 7, 2019

Accepted: September 11, 2019

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  5. Саржевский В.О., Дубинина Ю.Н., Мельниченко В.Я. Диагностическое и прогностическое значение биохимических маркеров инфекционных осложнений высокодозной химиотерапии с аутологичной трансплантацией гемопоэтических стволовых клеток при злокачественных лимфопролиферативных заболеваниях. Клиническая онкогематология. 2017;10(1):113–9. doi: 10.21320/2500-2139-2017-10-1-113-119.

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The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity

KD Kaplanov1,2,3, TYu Klitochenko1,3, AL Shipaeva1, MN Shirokova1, IV Matveeva1, NB Lavrishina1

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

2 Volgograd Medical Research Center, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

3 Volgograd State Medical University, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

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

For citation: Kaplanov KD, Klitochenko TYu, Shipaeva АL, et al. The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity. Clinical oncohematology. 2017;10(3):358–65 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-358-365


Background. Among the newly diagnosed patients with Hodgkin’s lymphoma (HL), the proportion of elderly patients account for 15–35 %. In > 60 age group the choice of antitumor treatment requires an more individualised approach compared to a younger population. The ABVD regimen is acceptable in terms of efficiency and hematological toxicity, but is associated with a high risk of bleomycine-induced pulmonary complications. In ≥ 60 age group the morbitity and mortality of pulmonary complications account for 24 % and 18 %, respectively.

Aim. We aimed to evaluate the efficacy of the IVDG regimen in comparison with ABVD by the principle of “non-inferiority”.

Materials & Methods. This single centre, prospective, controlled, randomised study was started in 2009. The study included all primary patients aged ≥ 60 years with verified HL, regardless of the number and severity of comorbidities. The ABVD regimen was administered in 17 patients, and 20 patients received IVDG. The median age in the ABVD and IVDG groups was 67 and 70 years, respectively. The advanced stages of HL were reported in 13 (65 %) patients on IVDG, and in 12 (71 %) patients on ABVD (p = 0.9). Both of the groups were comparable in terms of the prevalence of chronic heart failure and chronic obstructive pulmonary disease. The prevalence of ischemic heart disease was higher in the IVDG group (n = 16) compared to ABVD (n = 8) (p = 0.04).

Results. IVDG and ABVD groups did not differ in the frequency of complete (14 and 10) and partial (3 and 4) remissions. Differences in 5-year overall survival were insignificant: 49 % in the IVDG group, vs 22 % in ABVD group (p = 0.41). No infectious or hemorrhagic complications were observed in both groups. The incidence of drug-induced pulmonary fibrosis after treatment was significantly lower in the IVDG group (n = 0) vs ABVD group (n = 4; 24 %) (p = 0.004).

Conclusion. The IVDG regimen may be used as first line treatment for HL in the elderly patients, especially in those having cardiac or pulmonary comorbidities. Compared to ABVD the IVDG regimen had similar efficacy and more beneficial safety profile in terms of cardiovascular and pulmonary toxicity.

Keywords: Hodgkin’s lymphoma, elderly patients, comorbidity, chemotherapy.

Received: December 22, 2016

Accepted: March 5, 2017

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WT1 Gene Overexpression in Oncohematological Disorders: Theoretical and Clinical Aspects (Literature Review)

NN Mamaev, YaV Gudozhnikova, AV Gorbunova

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Nikolai Nikolaevich Mamaev, DSci, Professor, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +(7)911-760-50-86; e-mail:

For citation: Mamaev NN, Gudozhnikova YaV, Gorbunova AV. WT1 Gene Overexpression in Oncohematological Disorders: Theoretical and Clinical Aspects (Literature Review). Clinical oncohematology. 2016;9(3):257-64 (In Russ).

DOI: 10.21320/2500-2139-2016-9-3-257-264


The article discusses recent data on the WT1 gene overexpression phenomenon in patients with acute leukemias, myelodysplastic syndromes, chronic myeloid leukemia, non-Hodgkin’s lymphomas, and multiple myeloma. It demonstrates that monitoring of the WT1 gene overexpression proves to be effective during the posttransplantation period, as well as after the induction chemotherapy. This approach may be applied in diagnosing the minimal residual disease and early detection of leukemia relapses, as well as their timely and controlled treatment. There are other promising fields of research, such as testing autografts for the presence or absence of tumor elements, as well as evaluation of the efficacy of induction chemotherapy in high risk patients.

Keywords: WT1 gene overexpression phenomenon, hematopoietic stem cell transplantation, chemotherapy, molecular treatment monitoring.

Received: February 8, 2016

Accepted: March 30, 2016

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Low Dose Cytarabine and Cladribine for Treatment of Relapsed or Refractory Acute Myeloid Leukemia: Clinical Experience

SV Gritsaev, II Kostroma, AA Kuzyaeva, IM Zapreeva, EV Litvinskaya, LV Stelmashenko, SA Tiranova, IS Martynkevich, NA Potikhonova, KM Abdulkadyrov

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

For correspondence: Sergei Vasil’evich Gritsaev, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-54-68; e-mail:

For citation: Gritsaev SV, Kostroma II, Kuzyaeva AA, et al. Low Dose Cytarabine and Cladribine for Treatment of Relapsed or Refractory Acute Myeloid Leukemia: Clinical Experience. Clinical oncohematology. 2016;9(1):48–53 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-48-53


Aim. The aim of this paper is to evaluate the effectiveness of low dose cytarabine (Ara-C) combined with cladribine for the treatment of relapsed or refractory acute myeloid leukemia (AML) and to determine clinical and lab factors associated with response to the therapy.

Methods. Data of 10 patients aged 26–58 years (median 48 years) were analyzed. The diagnoses were de novo AML (7 patients), secondary AML (sAML) (2 patients) and refractory anemia with excess of blasts (RAEB-2) (1 patient). Four patients had primary refractory AML. Relapse was diagnosed in 3 patients. The induction scheme 7+3 was ineffective in patient with RAEB-2. There was no response to any kind of therapy in sAML patients. The treatment scheme under trial consisted of Ara-C 10–15 mg/m2 subcutaneously twice a day for 1–14 days and cladribine 5 mg/m2 intravenously once a day for 1–5 days. The course was repeated in case of at least two-fold decrease in bone marrow blasts level in a punctate versus baseline. Medical examination and maintenance therapy were performed in accordance with protocols approved by the clinic.

Results. According to the protocol, the patients received 1–2 courses. Response was achieved in 5 patients: 2 patients achieved complete response (CR) and 3 achieved partial response (PR). The most common complication was hematologic toxicity. All patients received transfusions of blood components. No lethal outcomes were observed within 8 weeks. The duration of the response was 2 to 3 months. During this period of time, allogeneic stem cell transplantation was performed in 2 patients with CR; however, in one patient, the conditioning regimen began at the same time with the increase in blast cell count in the bone marrow. The search for unrelated donors of hematopoietic stem cells for 2 patients with CR was begun. The distinct features of all patients with CR and PR were the following factors: de novo AML, absence of FLT3 or c-KIT mutations and the course duration was not less than 10 days.

Conclusion. Low dose Ara-C in combination with cladribine may be considered a treatment option for some patients with relapsed or refractory de novo AML.

Keywords: acute myeloid leukemia, relapse, refractory, chemotherapy, low dose cytarabine, cladribine.

Received: June 4, 2015

Accepted: October 8, 2015

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Surgical Treatment of Perianal Infectious Complications in Hematologic Clinic

S.V. Shtyrkova, S.R. Karagyulyan, K.I. Danishyan, S.K. Kravchenko, V.V. Troitskaya, L.A. Kuz’mina

Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Svetlana Vital’evna Shtyrkova, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-61-91; e-mail:

For citation: Shtyrkova S.V., Karagyulyan S.R., Danishyan K.I., Kravchenko S.K., Troitskaya V.V., Kuz’mina L.A. Klin. Onkogematol. 2015; 8(3): 337-42. (In Russ.)


Background & Aims. In general surgical practice, the perianal infection is considered an emergency surgical defect and requires an urgent surgical intervention. However, the perianal infection complicating leukemia has its peculiar clinical manifestations and requires revision of the traditional approach. The aim of the study is to mark out possible risk factors of development of the perianal infection in patients with hematologic malignancy and to estimate efficacy of various treatment options.

Methods. Results of examination and treatment of 143 oncohematological patients with inflammatory anorectal pathology are presented. Among them, the largest group consisted of 110 patients with anal fissures and fistulas.

Results. The study demonstrated that the main mechanism of infection in these patients was associated with local damage of the wall of the anal canal: mechanical trauma ® crack ® paraproctitis or inflammation due to diarrhea or toxic effects of drugs ® anusitis ® cryptitis ® paraproctitis. In case of paraproctitis in patients with leukopenia, a combined parenteral antibiotic therapy is considered to be the basic treatment method.

Conclusion. In oncohematological patients when the underlying disease as well as the upcoming chemotherapy can lead to severe immunosuppression, the presence of persistent defect of the anal canal wall (anal fissure, fistula) should be considered as an indication for surgery. The surgical procedure reduces the risk of local inflammation and septic complications.

Keywords: perianal infection, disease of the anal canal, hematologic malignancies, leukemia, chemotherapy.

Received: May 19, 2015

Accepted: June 3, 2015

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Efficacy and Toxicity of Therapy for Patients with Intermediate-Risk Hodgkin’s Lymphoma: Results of Multicenter Randomized Study

IA Kryachok1, AA Amdiev2, IB Titorenko1, EM Aleksik1, EO Ulyanchenko1, OI Novosad1, ES Filonenko1, MI Kasich2, MYa Kiseleva2

1 National Cancer Institute, 33/43 Lomonosova str., Kyiv, Ukraine, 03022

2 V.M. Efetov Crimean National Clinical Oncology Dispensary, 49a Bespalova str., Simferopol, Russian Federation, 295023

For correspondence: Alim Anvarovich Amdiev, 49a Bespalova str., Simferopol, Russian Federation, 295023; Tel.: +38(0652)60-22-09; e-mail:

For citation: Kryachok IA, Amdiev AA, Titorenko IB, et al. Efficacy and Toxicity of Therapy for Patients with Intermediate-Risk Hodgkin’s Lymphoma: Results of Multicenter Randomized Study. Clinical oncohematology. 2015;8(3):281–6 (In Russ).


Objective. To study the efficacy and toxicity of various treatment schemes for patients with intermediate-risk Hodgkin’s lymphoma (HL).

Methods. This article presents an analysis of the immediate results of complex treatment of 103 intermediate-risk HL patients (stage IIA and IIB with one or more unfavorable prognostic factors), who have been treated at the National Cancer Institute (Kyiv) and the Crimean Oncology Dispensary (Simferopol) from 2009 to 2014 (study group). Patients were divided into two study groups and treated with 6xBEACOPP-esc or 2xBEACOPP-esc + 4xABVD, followed by radiotherapy on the affected areas at a dose of 30–36 Gy in both groups. The control group included 53 patients who received treatment according to the 6xABVD scheme, followed by radiotherapy on the affected areas at a dose of 30–36 Gy over the period from 2000 to 2008. The immediate efficiency of the therapy, as well as its toxicity was evaluated.

Results. The study results demonstrated that treatment of the intermediate-risk HL patients that included 6xBEACOPP-esc and 2xBEACOPP-esc + 4xABVD proved to be an effective approach. Overall immediate efficacy of 2xBEACOPP-esc + 4xABVD protocol with subsequent radiation therapy was 95.83 %, and that of the 6xBEACOPP-esc was 96.36 %, which was significantly higher than the efficacy in the control group (83.02 %; < 0.05). The toxicity level of the therapy was lower in the 2xBEACOPP-esc + 4xABVD group than that in the 6xBEACOPP-esc group (63.19 % and 83.03 %, respectively, < 0.001).

Conclusion. Treatment of patients with intermediate-risk HL with 2xBEACOPP-esc + 4xABVD is comparable to that with 6xBEACOPP-esc, but it demonstrates a better toxicity profile.

Keywords: Hodgkin’s lymphoma, chemotherapy, efficacy, toxicity.

Received: March 31, 2015

Accepted: May 31, 2015

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Importance of biochemical studies of brain natriuretic peptide in patients with diffuse large B-cell lymphoma

M.O. Yegorova, Ye.N. Komolova, and S.Ye. Samsonova

Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation


In this study, we measured the levels of the brain natriuretic peptide (BNP) in the blood of patients with diffuse large B-cell lymphoma (DBCL) before and after polychemotherapy. The study included 10 patients: 6 males and 4 females at the age of 39 to 63 (mean age = 51 ± 12). The control group consisted of 20 virtually healthy donors. It was shown that measurements of BNP plasma levels in DBCL could identify the patients with the high risk of heart failure. Screening tests with determination of BNP levels can influence the choice of chemotherapy for DBCL.

Keywords: diffuse large B-cell lymphoma, chemotherapy, BNP, myocardial infarction, congestive left ventricular heart failure.

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Pulmonary MALT-lymphoma: case report and literature review

A.K. Morozova, N.G. Gabeeva, and E.E. Zvonkov

Hematology Research Center, RF Ministry of Health, Moscow, Russian Federation


This article presents a rare case of pulmonary MALT-lymphoma and literature review. An elderly patient with pulmonary MALT lymphoma was successfully treated according to R-B (rituximab + bendamustine) chemotherapy program. After 6 R-B courses, sustained remission with minimal toxicity and good tolerability was achieved.

Keywords: pulmonary MALT-lymphoma, chemotherapy, bendamustine

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