treatment

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

LYMPHOID TUMORS , , ,

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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Modern Aspects of Diagnosis and Treatment of Anaplastic Large Cell Lymphoma in Children (Literature Review)

LYMPHOID TUMORS , , ,

AS Levashov1, TT Valiev1, AM Kovrigina2, AV Popa1, GL Mentkevich1

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

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

For correspondence: Andrei Sergeevich Levashov, scientific worker, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(916)233-05-75; e-mail: andreyslevashov@mail.ru

For citation: Levashov AS, Valiev TT, Kovrigina AM, et al. Modern Aspects of Diagnosis and Treatment of Anaplastic Large Cell Lymphoma in Children (Literature Review). Clinical oncohematology. 2016;9(2):199–207 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-199-207

ABSTRACT

Anaplastic large cell lymphoma (ALCL) includes different types of the disease that are heterogeneous according to clinical, morphological, immunological, cytogenetic and molecular biological features. The review demonstrates not only main clinical and morphoimmunological characteristics of ALCL, but also presents data about expression and prognostic significance of STAT3, pSTAT3tyr705, and survivin (transcription factor). It demonstrates the value of defining the minimal disseminated disease (the minimal disseminated disease is evaluated using the PCR test before initiation of the treatment, and the minimal residual disease is evaluated during the treatment and after its completion), and clinical and molecular biological prognostic factors are also identified. There is still no a standard therapeutic regimen for pediatric ALCL patients. However, the following therapeutic protocols are considered most effective: NHL-BFM 90/95, CCG5941, SFOP-LM 89/91, UKCCSG, ALCL99-Vinblastine, POG АРО 9315, AIEOP LNH-92/97. Treatment outcomes are presented in this paper. Particular attention is paid to different molecular biological markers that allow further improvement of patients’ stratification in risk groups and possible use of target medications (multikinase inhibitors and monoclonal antibodies) improving the therapy outcomes.

Keywords: anaplastic large cell lymphoma, diagnosis, treatment, children.

Received: February 3, 2016

Accepted: February 10, 2016

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Treatment of Advanced Stage Hodgkin’s Lymphoma: Literature Review

REVIEWS , , , ,

AA Leont’eva, EA Demina

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

For correspondence: Anna Aleksandrovna Leont’eva, graduate student, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-90-89; e-mail: aurevoir-nut@yandex.ru

For citation: Leont’eva AA, Demina EA. Treatment of Advanced Stage Hodgkin’s Lymphoma: Literature Review. Clinical oncohematology. 2015;8(3):255–66 (In Russ).

ABSTRACT

Over the past decade, major research centers with large databases in Europe and the USA have conducted a comprehensive analysis of the effectiveness of treatment programs, delayed treatment-related complications and long-term survival of patients with advanced stage Hodgkin’s lymphoma. This analysis allowed us to develop new, more effective programs and introduce them into practical medicine, as well as to start searching for less toxic treatment options. However, in Russian scientific literature, this complex analysis has not been presented. Available publications and scientific investigations cover only some aspects of diagnosis and treatment of Hodgkin’s lymphoma or selectively discuss the problem of complications. The proposed literature review allows the reader to see the changes in the approach to management of advanced-stage Hodgkin’s lymphoma over the last 75 years: from absolutely pessimistic prognosis for the disease to modern high achievements with further improvement of treatment options for this disease.

Keywords: Hodgkin’s lymphoma, advanced stages, treatment, effectiveness of treatment, toxicity.

Received: February 20, 2015

Accepted: May 28, 2015

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Rare Disease — Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma: Literature Review and Own Data

LYMPHOID TUMORS , , , ,

E.A. Demina1, G.S. Tumyan1, A.A. Chekan1, M.Yu. Kichigina1, A.S. Antipova1, N.A. Probatova1, A.I. Pavlovskaya1, N.V. Kokosadze1, A.M. Kovrigina2, O.P. Trofimova1, E.A. Osmanov1

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

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

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

For citation: Demina E.A., Tumyan G.S., Chekan A.A., Kichigina M.Yu., Antipova A.S., Probatova N.A., Pavlovskaya A.I., Kokosadze N.V., Kovrigina A.M., Trofimova O.P., Osmanov E.A. Rare Disease — Nodular Lymphocyte-Predominant Hodgkin’s Lymphoma: Literature Review and Own Data. Klin. Onkogematol. 2014; 7(4): 522–532 (In Russ.).

ABSTRACT

Nodular lymphocyte-predominant Hodgkin’s lymphoma (NLPHL) is a rare disorder; it constitutes only 5 % of all cases of Hodgkin’s lymphoma (the morbidity rate is 1.5 per one million). The disease differs from classical Hodgkin’s lymphoma (cHL) in both immunohistochemical (marked CD20 expression in LP cells) and clinical features (prevalence of the early stage disease, indolent course with delayed relapses and trends toward transformation into diffuse large B cell lymphoma). Since the number of patients in prospective NLPHL-focused trials is limited, treatment algorithms have been based on retrospective data; these are usually obtained from cHL and indolent B cell lymphoma treatment strategies. Patients rarely die from NLPHL; in fact, secondary malignancies and other treatment related toxicities generally contribute to overall mortality. Over the past decade, there has been a series of NLPHL-related publications describing prescription of rituximab for newly diagnosed diseases and for relapses, including patients at high risk of diseases transformation. Besides, the role of the “wait and watch”, radiation treatment, and chemotherapy has been discussed. Our own experience in the use of rituximab in NLPLH patients demonstrated its efficacy at different stages and at different phases of the disease.

Keywords: nodular lymphocyte-predominant Hodgkin’s lymphoma, diagnosis, clinical characteristics, treatment, rituximab.

Accepted: September 8, 2014

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Lymphomas in HIV-Infected Patients: Literature Review

REVIEWS , , , , , , ,

A.V. Pivnik1, N.V. Seregin2, Yu.G. Parkhomenko3,4, O.A. Tishkevich4, A.M. Kovrigina5, Е.B. Likunov6

1 N.N. Pletnev Moscow Clinical Research Center, Department of Health, Moscow, Russian Federation

2 Moscow Municipal Cancer Dispensary No. 3, Moscow, Russian Federation

3 Research Institute of Human Morphology, RAMS, Moscow, Russian Federation

4 Clinical Infectious Diseases Hospital No. 2, Department of Health, Moscow, Russian Federation

5 Hematology Research Center, RF MH, Moscow, Russian Federation

6 American Medical Center, Moscow, Russian Federation

Address correspondence to: pivnikav@gmail.com

For citation: Pivnik A.V., Seregin N.V., Parkhomenko Yu.G., Tishkevich O.A., Kovrigina A.M., Likunov E.B. Lymphomas in HIV-Infected Patients: Literature Review. Klin. onkogematol. 2014; 7(3): 264–77 (In Russ.).

ABSTRACT

This review presents data on incidence, pathogenesis, diagnosis, and treatment of lymphoid malignancies in HIV-infected patients. Articles published by Russian and foreign authors are being reviewed. The principle role of decreased CD4+ lymphocyte count in development of secondary diseases in HIV patients is emphasized. Data on the structure of death causes in HIV-infected patients published by Russian authors are presented. They demonstrate that lymphoma is the 5th most common death cause (of 6 leading death causes). Hodgkin’s lymphoma in HIV-infected patients is not discussed in the review, because its pathogenesis differs from that of aggressive lymphomas and requires a separate discussion.

Keywords: lymphomas in HIV-infected patients, HIV, AIDS, secondary disorders, death causes, pathogenesis, diagnosis, treatment.

Accepted: May 15, 2014

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Optimization of diagnosis and treatment of Burkitt’s lymphoma in children, adolescents, and young adults

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , , , ,

T.T. Valiyev1, Ye.A. Baryakh2, P.A. Zeynalova3, A.M. Kovrigina2, S.K. Kravchenko2, T.N. Obukhova2, N.А. Falaleyeva3, A.I. Senderovich3, I.N. Serebryakova3, I.V. Kaminskaya1, A.S. Levashov1, and G.L. Mentkevich1

1 Pediatric Oncology and Hematology Research Institute, N.N. Blokhin Russian Cancer Center, Moscow, Russian Federation

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

3 Clinical Oncology Research Institute, N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation

ABSTRACT

We present the combined experience of the leading centers in diagnosis and treatment of Burkitt’s lymphoma (BL) in children, adolescents, and young adults, that is the first one in the national scientific literature. It includes immunolomorphologic and cytogenetic criteria of BL. The clinical features of BL in various age groups and treatment outcomes according to B-NHL-BFM 90/95 and CODOX-M/IVAC programs are described. Also, the treatment outcomes according to the original national LB-M-04 protocol are shown. The place of rituximab in BL treatment is discussed.

Keywords: Burkitt’s lymphoma, children, adolescents, young adults, clinical features, diagnosis, treatment.

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Management of relapsed and refractory multiple myeloma: literature review and our data. Part III

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , , , , , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

Abstract

Advances in treatment options for patients with multiple myeloma have made a significant impact on overall survival and have helped to achieve the rates of response and duration of remission previously not unachievable with standard chemotherapy-based approaches. These improvements are due, in a large part, to the development of the novel agents, including bortezomib, thalidomide, and lenalidomide, each of which has substantial single-agent activity. Combinations of bortezomib, thalidomide, and lenalidomide with conventional agents or among each other have resulted in enhanced response rates and efficacy. However, when patients are unresponsive to immunomodulatory drugs and bortezomib, the prognosis becomes poor. A number of novel agents are being tested in multiple myeloma, but relapsed/refractory multiple myeloma still represents a challenge and difficult area for drug development. Therefore, the new agents are needed. In addition, a large number of second- or third-generation agents are also in clinical development, such that the repertoire of available treatment options continues to expand. Such agents as carfilzomib, pomalidomide, vorinostat, panobinistat, romidepsin, perifosine, tanespimycin, bendamustine, and elotuzumab are just a few out of many exciting new compounds that are being tested in phases I, II, or III of clinical trials for relapsed patients. This review covers the new strategies, based on clinical trials and our own data and intended for optimizing treatment outcomes in relapsed/refractory multiple myeloma. We describe the various classes of novel drugs under investigation and discuss the pros and cons of the data obtained in preclinical and clinical studies. The adverse effects of the new drugs are presented in detail.

Keywords: multiple myeloma, relapsed/refractory multiple myeloma, bortezomib, thalidomide, lenalidomide, carfilzomib, pomalidomide, treatment, complete remission, overall survival, neuropathy.

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Stable donor hematopoiesis reconstitution after post-transplantation relapse of acute myeloid leukemia in patient with inv(3)(q21q26), –7 and EVI1 oncogene overexpression treated by donor lymphocyte infusions and hypomethylating agents

BONE MARROW TRANSPLANTATION , , , , , ,

N.N. Mamaev, A.V. Gorbunova, T.L. Gindina, O.A. Slesarchuk, V.N. Ovechkina, S.N. Bondarenko, O.V. Goloshchapov, V.M. Kravtsova, and B.V. Afanasev

I.P. Pavlov Saint Petersburg State Medical University, R.M. Gorbacheva Institute of Pediatric Oncology, Hematology and Transplantology, Saint Petersburg, Russian Federation

ABSTRACT

We present the case of successful treatment of post-transplantation relapse of prognostically unfavorable AML with inv(3)(q21q26), –7 and EVI1 oncogene overexpression, when stable donor hematopoiesis reconstitution was achieved due to one high-dose cytarabine course, DLI, and hypomethylating agents (decitabine, 5-azacitidine). Possible molecular mechanisms of this effect are discussed with respect to the new approaches to management of such patients.

Keywords: acute myeloid leukemia, inv(3)(q21q26), EVI1 high expression, hematopoietic stem cell transplantation, relapse, treatment, donor lymphocyte infusions, hypomethylating agents.

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REFERENCES

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Evolution of concepts for diagnosis and treatment of Burkitt’s lymphoma

EXPERIMENTAL STUDIES , , ,

T.T. Valiev1 and E.A. Baryakh2

1 Pediatric Oncology and Hematology Institute, N.N. Blokhin Russian Cancer Research Center, RAMS, Moscow, Russian Federation

2 Hematology Research Center, RF MH, Moscow, Russian Federation

ABSTRACT

The issues of diagnosis and treatment of the most aggressive lymphoid tumor, namely, Burkitt’s lymphoma (BL), are presented in the historical context. The clinical and laboratory features of endemic and sporadic BL variants are described. Possible mechanisms of Epstein-Barr virus and Plasmodium falciparum involvement in BL pathogenesis are suggested. Also, the morphologic, immunologic and cytogenetic BL diagnostic criteria are described. Based on molecular and genetic features, the issues of differential diagnosis with the heterogeneous group of diffuse large B-cell and highly aggressive mature B-cell lymphomas with additional proto-oncogene aberrations («double» and «triple» hit lymphomas) are presented. BL therapy and the role of rituximab in it is emphasized.

Keywords: Burkitt’s lymphoma, clinical presentation, diagnosis, treatment.

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Multiple myeloma (management of newly diagnosed patients): literature review and our on data. Part II

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , , , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

ABSTRACT

Over the last decades, survival rates for young patients with multiple myeloma markedly increased mainly due to the use of autologous stem cell transplantation (ASCT) and new highly efficacious rescue therapies. In patients with multiple myeloma over 65 years of age, a combination of melphalan and prednisone (MP) is traditionally used. Introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors substantially changed the therapeutic approach to the disease. Many double-, triple-, and quadruple-agent combinations were studied in the patients with newly diagnosed multiple myeloma. It was established that the achievement of complete response (CR) is an independent predictor of prolonged progression-free survival (PFS) and overall survival (OS). The data from prospective trials completed suggest that the best available strategy to achieve high CR rates and prolong its duration includes an induction therapy with a triple-agent bortezomib- or IMiDs-based regimen followed by ASCT and consolidation/maintenance with IMiDs or proteasome inhibitors. The vast majority of elderly patients with MM are ineligible for ASCT. Introduction of novel agents such as thalidomide, bortezomib, or lenalidomide considerably improved the treatment outcomes. MPT (MP + thalidomide), VMP (MP + bortezomib), and MPR-R (MP + lenalidomide) regimens are currently regarded as the new standards of care for elderly patients with multiple myeloma. The prognosis for multiple myeloma is determined by numerous factors, all of which should be considered when choosing the initial therapy. This review covers the new strategies based on the current studies being conducted that are aimed at optimizing treatment outcomes in the patients with newly diagnosed multiple myeloma.

Keywords: multiple myeloma, bortezomib, thalidomide, lenalidomide, treatment, complete remission, overall survival, neuropathy, autologous stem cell transplantation

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