Intermediate Results of Prospective, Randomized, Comparative Study of NHL BFM-90 and СНОЕР Efficacy in Primary ALK-Positive Anaplastic Large-Cell Lymphoma

LG Gorenkova1, SK Kravchenko1, EE Klebanova1, AM Kovrigina1, KA Sychevskaya1, EG Gemdzhian1, ES Nesterova1, YaK Mangasarova1, AU Magomedova1, AV Misyurin2, YuV Sidorova1, TN Obukhova1

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

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

For correspondence: Liliya Gamilevna Gorenkova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: l.aitova@mail.ru

For citation: Gorenkova LG, Kravchenko SK, Klebanova EE, et al. Intermediate Results of Prospective, Randomized, Comparative Study of NHL BFM-90 and СНОЕР Efficacy in Primary ALK-Positive Anaplastic Large-Cell Lymphoma. Clinical oncohematology. 2020;13(4):382–8. (In Russ).

DOI: 10.21320/2500-2139-2020-13-4-382-388


ABSTRACT

Aim. To compare NHL BFM-90 and CHOEP efficacy in adult patients with ALK-positive anaplastic large-cell lymphoma (ALK+ ALCL).

Materials & Methods. Within the period from June 2014 to December 2019 the prospective randomized comparative study at the National Research Center for Hematology in Moscow included 23 ALK+ ALCL patients. In one study arm (n = 11) CHOEP was administered, whereas the other one (n = 12) received high-dose chemotherapy (CT) according to NHL BFM-90 protocol. The median age of patients in both arms was 33 and 40 years, respectively.

Results. Overall survival (OS) and event-free survival (EFS) within 3 years were 91 % in the arm receiving CHOEP (this protocol was administered to all 11 patients), and 100 % in the arm receiving NHL BFM-90 (complete remission was achieved in all patients). Due to its toxicity NHL BFM-90 was fully implemented in 9 out of 12 patients. The 3-year OS and EFS in the CHOEP and NHL BFM-90 arms are comparable, and the difference between them is not significant.

Conclusion. In ALK+ ALCL treatment high-dose CT according to NHL BFM-90 protocol has no advantage in terms of the 3-year OS and EFS compared to less toxic regimen CHOEP. A larger sample of patients is required to achieve significant results, which will further lead to a final judgement on feasibility of high-dose regimens in the treatment of adult patients with ALK+ ALCL.

Keywords: ALK-positive anaplastic large-cell lymphoma, ALK+ ALCL, treatment, adults, CHOEP, NHL BFM-90, survival.

Received: April 8, 2020

Accepted: August 30, 2020

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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: drdemina@yandex.ru

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


ABSTRACT

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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Non-Hodgkin’s Lymphomas in Children: 25-Year Clinical Experience

TT Valiev, AV Popa, AS Levashov, ES Belyaeva, NS Kulichkina, BV Kurdyukov, RS Ravshanova, GL Mentkevich

Scientific Research Institute of Pediatric Oncology and Hematology, NN Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Timur Teimurazovich Valiev, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-98-69; e-mail: timurvaliev@mail.ru

For citation: Valiev TT, Popa AV, Levashov AS, et al. Non-Hodgkin’s Lymphomas in Children: 25-Year Clinical Experience. Clinical oncohematology. 2016;9(4):420–37 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-420-437


ABSTRACT

Background & Aims. Current polychemotherapeutic protocols based on differentiated and risk-adopted approaches permitted to consider non-Hodgkin’s lymphomas (NHL) potentially curable diseases although they had been considered fatal previously. The aim of this study is to summarize and analyze outcomes of NHL therapy over a 25-year period.

Methods. 246 patients were enrolled in the study. They were treated in the department of chemotherapy of hemoblastoses in the Scientific Research Institute of Pediatric Oncology and Hematology under the NN Blokhin Russian Cancer Research Center over the period of 25 years: from April 1, 1991, till June 1, 2016. B-NHL-BFM 90/95 protocols and a modified B-NHL-BFM 95 protocol (with rituximab) were used for B-cell NHLs (n = 130). Patients with lymphocytic leukemia (n = 75) were treated using ALL-mBFM 90/95 and ALL IC-BFM 2002 protocols. 21 patients with anaplastic large cell lymphomas (ALCL) received treatment according to the B-NHL-BFM 90/95 protocol, and 20 patients received the НИИ ДОГ-АККЛ-2007 protocol.

Results. Taking into account clinical and immunological characteristics of ALCL, the authors invented an original НИИ ДОГ-АККЛ-2007 protocol. Special attention was paid to potential modification of standard treatment regimens for B-cell NHL by adding rituximab. The article demonstrates the evolution in prescription of rituximab for B-cell NHL and possibilities for reduction of the total number of polychemotherapy cycles for late-stage tumors without deterioration of treatment outcomes.

Conclusion. The obtained results permit to conclude that introduction of achievements of oncoimmunology, molecular biology, and cytogenetics will become the basis for further modification of existing treatment options for NHL.


Keywords: Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, T- and B-cell lymphoblastic lymphomas, treatment, children.

Received: June 12, 2016

Accepted: June 17, 2016

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Stevens-Johnson Syndrome after Treatment of Female Patient with Small Lymphocytic B-Cell Lymphoma, Autoimmune Hemolytic Anemia and Antiphospholipid Antibody Syndrome with Rituximab

AL Melikyan, IN Subortseva, AM Kovrigina, TI Kolosheinova, EK Egorova, EI Pustovaya

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

For correspondence: Irina Nikolaevna Subortseva, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-44-71; e-mail: soubortseva@yandex.ru

For citation: Melikyan AL, Subortseva IN, Kovrigina AM, et al. Stevens-Johnson Syndrome after Treatment of Female Patient with Small Lymphocytic B-Cell Lymphoma, Autoimmune Hemolytic Anemia and Antiphospholipid Antibody Syndrome with Rituximab Clinical oncohematology. 2017;10(1): 120–7 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-120-127


ABSTRACT

Stevens-Johnson syndrome is a severe delayed type systemic allergic reaction which affects the skin and mucous membranes. In adults, Stevens-Johnson syndrome is usually caused by the administration of drugs or a malignant process. The paper presents a case of Stevens-Johnson syndrome after the treatment of a female patient with small lymphocytic B-cell lymphoma, autoimmune hemolytic anemia and antiphospholipid antibody syndrome with rituximab. A rare combination of Stevens-Johnson syndrome and small lymphocytic B-cell lymphoma of small lymphocytes, as well as the development of severe delayed type systemic allergic reaction to introduction of rituximab are of special interest. A detailed medical history and the clinical manifestations of the disease allowed to diagnose Stevens-Johnson syndrome at early stages and prescribe an adequate therapy. As a result of the treatment, the patient’s condition has improved considerably. Symptoms of general toxicity were arrested completely; there was a complete epithelization of erosive defects. Therefore, the presented clinical observation shows that timely diagnosis, complex drug therapy, and comprehensive care can cure the diseases as soon as possible and prevent complications.

Keywords: Stevens-Johnson syndrome, pathogenesis, clinical manifestations, diagnosis, treatment, rituximab.

Received: July 28, 2016

Accepted: December 6, 2016

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Primary Mediastinal (Thymic) Large B-Cell Lymphoma

GS Tumyan, IZ Zavodnova, MYu Kichigina, EG Medvedovskaya

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

For correspondence: Gayane Sergeevna Tumyan, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-98-29; e-mail: gaytum@mail.ru

For citation: Tumyan GS, Zavodnova IZ, Kichigina MYu, Medvedovskaya EG. Primary Mediastinal (Thymic) Large B-Cell Lymphoma. Clinical oncohematology. 2017;10(1):13–24 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-13-24


ABSTRACT

Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is one of the primary extranodal tumors and originates from thymic medulla B cells. The disease is more common in young women and declares itself by mainly locally advanced growth within the anterior upper mediastinum with frequent involvement of chest organs. PMBCL has specific morphological, immunological, and genetic characteristics that permit to differentiate it from other similar diseases: diffuse large В-cell lymphoma, nodular sclerosis Hodgkin’s lymphoma, and mediastinal gray zone lymphoma. Immunochemotherapy with subsequent irradiation of the residual mediastinal tumor is the standard treatment of PMBCL. No benefits of one drug therapy over another have been demonstrated to date in controlled studies. Application of new imaging techniques (PET/CT) may result in withdrawal of the radiotherapy in some PMBCL patients without impairment of delayed survival rates.

Keywords: primary mediastinal (thymic) large B-cell lymphoma, primary extranodal lymphomas, diagnosis, pathogenesis, morphological, immunological/genetic characteristics, treatment.

Received: August 22, 2016

Accepted: December 17, 2016

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Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region

VI Bakhtina1,2, IV Demko2, AN Narkevich2, DS Gushchin3

1 Regional Clinical Hospital, 3а Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

2 Professor VF Voyno-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

3 Norilsk Inter-District Hospital No. 1, Solnechnyi pr-d, 7a Norilsk, Russian Federation, 663300

For correspondence: Varvara Ivanovna Bakhtina, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022; Tel: +7(923)357-57-77; е-mail: doctor.gem@mail.ru

For citation: Bakhtina VI, Demko IV, Narkevich AN, Gushchin DS. Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region. Clinical oncohematology. 2016;9(4):413–419 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-413-419


ABSTRACT

Background & Aims. B-cellular chronic lymphocytic leukemia (CLL) is a disease with heterogeneous clinical manifestations and biological characteristics. The age of 70 % of patients is more than 65 years by the date of the diagnosis; most of them have several comorbidities. The aim of the study is to identify factors affecting the survival, as well as to determine causes of mortality in CLL patients (according to data from hematological hospitals of Krasnoyarsk Region).

Methods. In order to identify the most significant factors affecting the course and the outcome of CLL, a retrospective analysis of data on patients who died in hematological hospitals was carried out. 45 cases with the lethal outcome were registered within six years. All patients were under hematologist’s supervision after diagnosing the disease, and they were followed throughout the treatment period up to the lethal outcome.

Results. Тhe overall and progression-free survival depended, first of all, on the type of the first line therapy and its efficacy. The progression of the underlying disease and infectious complications became the main reason of the lethal outcome in CLL patients.

Conclusion. Most patients received ineffective treatment as first line therapy. The analysis of the comorbidities showed that a more effective chemotherapy could be performed with achievement of longer complete remissions.


Keywords: chronic lymphocytic leukemia, oncohematological diseases, comorbidities, survival, treatment.

Received: May 16, 2016

Accepted: June 17, 2016

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Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas

EA Demina

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

For correspondence: Elena Andreevna Demina, DSci, Professor, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7 (499)324-90-89; e-mail: drdemina@yandex.ru

For citation: Demina EA. Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas. Clinical oncohematology. 2016;9(4):398–405 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-398-405


ABSTRACT

The concept of total curability of Hodgkin’s lymphoma was introduced as early as in 1970s. However, 10–30 % of patients develop relapses; in addition, resistant tumors cannot be excluded. A high-dose chemotherapy with autologous hematopoietic stem cell transplantation is a modern treatment standard for relapses and refractory Hodgkin’s lymphomas. However, long-term remissions are achieved only in a half of these patients. The toxicity of effective first-line treatment regimens and insufficient effectiveness of regimens prescribed for relapses and refractory disease are the reason for further search of new therapeutic options for this malignant tumor. Invention of an immunoconjugate, brentuximab vedotin, became one of the new steps in the treatment of Hodgkin’s lymphomas. This review presents data on the pharmacological properties of the drug, the mechanism of the anti-tumor effect, as well as results of large international, randomized clinical trials.


Keywords: brentuximab vedotin, Hodgkin’s lymphoma, relapse, treatment.

Received: June 14, 2016

Accepted: June 17, 2016

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Non-Hodgkin’s Lymphomas in Children: 25-Year Clinical Experience

TT Valiev, AV Popa, AS Levashov, ES Belyaeva, NS Kulichkina, BV Kurdyukov, RS Ravshanova, GL Mentkevich

Scientific Research Institute of Pediatric Oncology and Hematology, NN Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Timur Teimurazovich Valiev, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-98-69; e-mail: timurvaliev@mail.ru

For citation: Valiev TT, Popa AV, Levashov AS, et al. Non-Hodgkin’s Lymphomas in Children: 25-Year Clinical Experience. Clinical oncohematology. 2016;9(4):420–37 (In Russ).

DOI: http://dx.doi.org/10.21320/2500-2139-2016-9-4-420-437


ABSTRACT

Background & Aims. Current polychemotherapeutic protocols based on differentiated and risk-adopted approaches permitted to consider non-Hodgkin’s lymphomas (NHL) potentially curable diseases although they had been considered fatal previously. The aim of this study is to summarize and analyze outcomes of NHL therapy over a 25-year period.

Methods. 246 patients were enrolled in the study. They were treated in the department of chemotherapy of hemoblastoses in the Scientific Research Institute of Pediatric Oncology and Hematology under the NN Blokhin Russian Cancer Research Center over the period of 25 years: from April 1, 1991, till June 1, 2016. B-NHL-BFM 90/95 protocols and a modified B-NHL-BFM 95 protocol (with rituximab) were used for B-cell NHLs (n = 130). Patients with lymphocytic leukemia (n = 75) were treated using ALL-mBFM 90/95 and ALL IC-BFM 2002 protocols. 21 patients with anaplastic large cell lymphomas (ALCL) received treatment according to the B-NHL-BFM 90/95 protocol, and 20 patients received the НИИ ДОГ-АККЛ-2007 protocol.

Results. Taking into account clinical and immunological characteristics of ALCL, the authors invented an original НИИ ДОГ-АККЛ-2007 protocol. Special attention was paid to potential modification of standard treatment regimens for B-cell NHL by adding rituximab. The article demonstrates the evolution in prescription of rituximab for B-cell NHL and possibilities for reduction of the total number of polychemotherapy cycles for late-stage tumors without deterioration of treatment outcomes.

Conclusion. The obtained results permit to conclude that introduction of achievements of oncoimmunology, molecular biology, and cytogenetics will become the basis for further modification of existing treatment options for NHL.

Keywords: Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, T- and B-cell lymphoblastic lymphomas, treatment, children.

Received: June 12, 2016

Accepted: June 17, 2016

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Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region

VI Bakhtina1,2, IV Demko2, AN Narkevich2, DS Gushchin3

1 Regional Clinical Hospital, 3а Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

2 Professor VF Voyno-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

3 Norilsk Inter-District Hospital No. 1, Solnechnyi pr-d, 7a Norilsk, Russian Federation, 663300

For correspondence: Varvara Ivanovna Bakhtina, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022; Tel: +7(923)357-57-77; е-mail: doctor.gem@mail.ru

For citation: Bakhtina VI, Demko IV, Narkevich AN, Gushchin DS. Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region. Clinical oncohematology. 2016;9(4):413–419 (In Russ).

DOI: http://dx.doi.org/10.21320/2500-2139-2016-9-4-413-419


ABSTRACT

Background & Aims. B-cellular chronic lymphocytic leukemia (CLL) is a disease with heterogeneous clinical manifestations and biological characteristics. The age of 70 % of patients is more than 65 years by the date of the diagnosis; most of them have several comorbidities. The aim of the study is to identify factors affecting the survival, as well as to determine causes of mortality in CLL patients (according to data from hematological hospitals of Krasnoyarsk Region).

Methods. In order to identify the most significant factors affecting the course and the outcome of CLL, a retrospective analysis of data on patients who died in hematological hospitals was carried out. 45 cases with the lethal outcome were registered within six years. All patients were under hematologist’s supervision after diagnosing the disease, and they were followed throughout the treatment period up to the lethal outcome.

Results. Тhe overall and progression-free survival depended, first of all, on the type of the first line therapy and its efficacy. The progression of the underlying disease and infectious complications became the main reason of the lethal outcome in CLL patients.

Conclusion. Most patients received ineffective treatment as first line therapy. The analysis of the comorbidities showed that a more effective chemotherapy could be performed with achievement of longer complete remissions.

Keywords: chronic lymphocytic leukemia, oncohematological diseases, comorbidities, survival, treatment.

Received: May 16, 2016

Accepted: June 17, 2016

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REFERENCES

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Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas

EA Demina

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

For correspondence: Elena Andreevna Demina, DSci, Professor, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7 (499)324-90-89; e-mail: drdemina@yandex.ru

For citation: Demina EA. Brentuximab Vedotin: New Possibilities for Treatment of Relapses and Refractory Hodgkin’s Lymphomas. Clinical oncohematology. 2016;9(4):398–405 (In Russ).

DOI: http://dx.doi.org/10.21320/2500-2139-2016-9-4-398-405


ABSTRACT

The concept of total curability of Hodgkin’s lymphoma was introduced as early as in 1970s. However, 10–30 % of patients develop relapses; in addition, resistant tumors cannot be excluded. A high-dose chemotherapy with autologous hematopoietic stem cell transplantation is a modern treatment standard for relapses and refractory Hodgkin’s lymphomas. However, long-term remissions are achieved only in a half of these patients. The toxicity of effective first-line treatment regimens and insufficient effectiveness of regimens prescribed for relapses and refractory disease are the reason for further search of new therapeutic options for this malignant tumor. Invention of an immunoconjugate, brentuximab vedotin, became one of the new steps in the treatment of Hodgkin’s lymphomas. This review presents data on the pharmacological properties of the drug, the mechanism of the anti-tumor effect, as well as results of large international, randomized clinical trials.

Keywords: brentuximab vedotin, Hodgkin’s lymphoma, relapse, treatment.

Received: June 14, 2016

Accepted: June 17, 2016

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