Role of Bendamustine in Treatment of Multiple Myeloma

O.M. Votyakova

N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian Federation

For citation: Votyakova O.M. Role of Bendamustine in Treatment of Multiple Myeloma. Klin. onkogematol. 2014; 7(3): 301–10 (In Russ.).

ABSTRACT

Bendamustine is an antineoplastic drug with a double mechanism of action combining the properties of alkylating compound and purine analog; it has a promising activity in multiple myeloma (MM). In 2013, Bendamustine (Ribomustin) was registered in Russia for treatment of patients older than 65 years of age with newly diagnosed ММ who are not eligible for high dose chemotherapy (HDC) with autologous transplantation of hemopoetic stem cells and who have clinical signs of neuropathy which impede the use of thalidomide and/or bortezomib. The review presents data on the product efficacy and safety both as monotherapy and in combination with glucocorticoids and target therapy (bortezomib, thalidomide, lenalidomide), in newly diagnosed and relapsed MM patients. The presented data permit to recommend bendamustine combined with glucocorticoids and novel drugs for MM patients with relapses and as the first line therapy in some patients with polyneuropathy who are not eligible for HDC with autologous transplantation of hemopoetic stem cells.


Keywords: multiple myeloma, bendamustine, ribomustin.

Address correspondence to: omvtk@yandex.ru

Accepted: May 23, 2014

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Brain Bioelectrical Activity and its Correlation with Personality Traits of Children and Adolescents with Lymphoid Malignancies

N.L. Gorbachevskaya1,3, E.I. Kuznetsova2, N.A. Polyakova1

1 Research Center of Mental Health of RAMS, Moscow, Russian Federation

2 N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian Federation

3 Scientific Research Center of Neurobiological Diagnostics of Inherited Mental Diseases in Moscow State University of Psychology & Education, Moscow, Russian Federation

For citation: Gorbachevskaya N.L., Kuznetsova E.I., Polyakova N.A. Brain Bioelectrical Activity and its Correlation with Personality Traits of Children and Adolescents with Lymphoid Malignancies. Klin. onkogematol. 2014; 7(3): 296–300 (In Russ.).


ABSTRACT

We assessed both cerebral bioelectrical activity and psychological markers of aggressiveness in 23 children and adolescents (11–16 years old) with lymphoid malignancies. The reference group consisted of 32 healthy adolescents. LT adolescents presented both normal and specific for this patient population aggressive behavioral patterns. The correlation between the EEG rhythm and the aggressive behavior. We obtained data on sex- and age-related aggressive behavior of adolescents. It was shown that the malignant process and chemotherapy significantly affected the central nervous system of children and adolescents; this effect manifests itself through specific psychological and neurophysiological disorders. The latter may be considered markers of neurotoхicity thus requiring psychological support and specific therapy during the anti-tumor treatment.


Keywords: children and adolescents (11–16 years), lymphoid malignancies, electroencephalogram, aggressive behavior, сhemotherapy, neurotoхicity.

Address correspondence to: gorbachevskaya@yandex.ru

Accepted: May 21, 2014

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REFERENCES

  1. Spear L.P. The adolescent brain and age-related behavioral manifestations. Neurosci. Biobehav. Rev. 2000; 24(4): 417–63.
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Procedural Considerations for Bone Marrow Trephine Biopsy

Yu.A. Krivolapov

I.I. Mechnikov North-Western State Medical University, Saint Petersburg, Russian Federation

For citation: Krivolapov Yu.A. Procedural Considerations for Bone Marrow Trephine Biopsy. Klin. onkogematol. 2014; 7(3): 290–5 (In Russ.).

ABSTRACT

The aim of the bone marrow trephine biopsy procedure is to obtain proper specimen for histological evaluation of hematopoietic tissue. The review provides information for indications and contraindications for the procedure. It also describes the procedure of trephine biopsy using a Jamshidi needle in detail and discusses procedural errors and potential complications.


Keywords: trephine biopsy, bone marrow examination, Jamshidi needle, biopsy technique.

Address correspondence to: krivolapov.yuri@gmail.com

Accepted: May 14, 2014

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REFERENCES

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  20. Islam A.B. Bone marrow aspiration before bone marrow core biopsy using the same bone marrow biopsy needle: a good or bad practice? J. Clin. Pathol. 2007; 60: 212–5. 21. Bain B.J. Bone marrow biopsy morbidity and mortality. Br. J. Haematol. 2003; 121(6): 949–51.

New molecular markers of CML progression

V.A. Misyurin1,2, A.V. Misyurin1,2, L.A. Kesayeva1,2, Yu.P. Finashutina1,2, Ye.N. Misyurina2, I.N. Soldatova1,2, A.A. Krutov2, N.A. Lyzhko1,2, T.V. Akhlynina1,2, A.Ye. Lukina3, T.I. Kolosheynova3, N.V. Novitskaya1, Ye.G. Arshanskaya4, Ye.G. Ovsyannikova5, R.A. Golubenko6, V.A. Lapin7, T.I. Pospelova8, V.A. Tumakov9, and A.Yu. Baryshnikov1

1 N.N. Blokhin Russian Cancer Research Center, Moscow, Russian Federation

2 GeneTechnology Medical Center, Moscow, Russian Federation

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

4 Moscow Hematological City Center, S.P. Botkin City Clinical Hospital, Moscow, Russian Federation

5 Astrakhan State Medical Academy, Astrakhan, Russian Federation

6 Orel Regional Clinical Hospital, Orel, Russian Federation

7 Hematological Center, Yaroslavl City Clinical Hospital #1, Yaroslavl, Russian Federation

8 Novosibirsk State Medical University, Novosibirsk, Russian Federation

9 Ivanovo Regional Clinical Hospital #1, Ivanovo, Russian Federation


ABSTRACT

In the contrast to Ph’-negative chronic myeloproliferative disorders (cMPD), chronic myelogenous leukemia (CML) is prone to rather early transformation into the later stage disease, known as the acceleration phase (AP) and blast crisis (BC). Myeloproliferative disorders are termed myeloproliferative neoplasms in the WHO classification, 2008. Molecular mechanisms underlying CML progression are unclear and still being studied. Recently, it was shown that progression of some malignancies was associated with activation and hyperexpression of some genes from the cancer-testis (CT) family. In this study, we evaluated the gene expression profile of CT genes (GAGE1, NY-ESO-1, MAGEA1, SCP1, SEMG1, SPANXA1, SSX1 and PRAME) in the blood of patients with initially diagnosed cMPD, as well as in the blood and bone marrow of CML patients in CP, AP and BC. It was found that activation of these eight CT genes expression was strongly correlated with CML progression to AP and BP. These data suggest that at least some of CT genes can be involved in CML evolution towards the terminal phases. Expression of these genes can be used as an early molecular predictor of CML progression to AP and BC.


Keywords: cancer-testis genes, PRAME, gene expression, chronic myelogenous leukemia, chronic myeloproliferative diseases

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Organizational principles of neurologist’s work in hematological in-patient clinic

K.A. Panyushin, Yu.M. Potapkina, Ye.V. Ignatyeva, T.A. Moskovskaya, T.V. Zhbrykunova, and O.A. Rukavitsyn

N.N. Burdenko Principal Military Clinical Hospital, RF Ministry of Defense, Moscow, Russian Federation


ABSTRACT

37 patients with hematological disorders underwent complex neurological evaluation including examination by a neurologist and electroneuromyography (ENMG). It is found that the considerable portion (51.3 %) of hematological patients shows signs of polyneuropathy as early as at the time of diagnosis. The data obtained indicate the possible need in specific neurological treatment just at the time of the initial tumor diagnosis prior to chemotherapy. The doses of chemotherapeutic agents should also be discussed in order to decrease their adverse effect on the peripheral nervous system. The results obtained suggest that detection of any hematological disorder necessitates examination by a neurologist, and neurological monitoring in a hematological in-patient clinic is an important part of management of patients with hematological malignancies.

Keywords: lymphoproliferative diseases, polyneuropathy, ENMG, polychemotherapy

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REFERENCES

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PCR-based clonality detection in angioimmunoblastic T-cell lymphoma

Yu.V. Sidorova, Ye.Ye. Nikulina, N.G. Chernova, L.G. Gorenkova, Ye.A. Gilyazitdinova, S.K. Kravchenko, A.M. Kovrigina, and A.B. Sudarikov

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


ABSTRACT

In this article, we discuss the issues of angioimmunoblastic T-cell lymphoma diagnosis, particularly the PCR-based methods of clonality detection. Assessments of T-and B-cell clonality was based on TCRG (Vg-Jg), TCRB (Vb-Jb, Db-Jb), IGH (FR1, FR2, and FR3), IGK (Vk-Jk, Vk/intron-Kde), or IGL (Vl-Jl) gene rearrangements in 15 patients. Clonal TCRG gene rearrangements were found in 66.7 % of primary biopsy samples. The combined use of primers for TCRG and TCRB gene rearrangements confirmed T-cell monoclonal population in most cases (86.7 %). The rate of B-cell clonality detection was 26.6 %. The presence of B-cell clones was not associated with monoclonal secretion in the blood or detecting Epstein-Barr virus positive B-cells in the biopsy samples. PCR-based clonality analysis is an important step in diagnosis of angioimmunoblastic T-cell lymphoma that enables identifying monoclonal origin of T-lymphocytes in most cases. However, when interpreting the results obtained by this method, it is necessary to consider the possibility of detecting B-cell monoclonal products of unclear origin.


Keywords: angioimmunoblastic T-cell lymphoma, PCR, clonality, T-cell antigen receptor

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REFERENCES

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Quality of life in adolescent and young adult Hodgkin’s lymphoma survivors

Ye.G. Arshanskaya1,2, S.V. Semochkin2,3, and A.G. Rumyantsev2,3

1 S.P. Botkin City Clinical Hospital, Moscow, Russian Federation

2 Federal Clinical-and-Research Center of Pediatric Hematology, Oncology, and Immunology n.a. Dmitriy Rogachev, Moscow, Russian Federation

3 N.I. Pirogov Russian National Research Medical University, RF Ministry of Health, Moscow, Russian Federation


ABSTRACT

Background. Deterioration of quality of life (QoL) and late complications of antitumor therapy for Hodgkin’s lymphoma (HL) are the important medical issues, since they mostly relate to young patients with a high life-expectancy.

Objective. The study was to compare QoL of HL survivors versus healthy young adults.

Methods. 56 (22 males and 34 females) HL survivors with a median age of 27.5 (range 22–41) were evaluated. For the purpose of comparison, 94 (44 males and 50 females) healthy subjects with a median age of 28.0 (range 22–46) were enrolled into the study of QoL. All HL survivors were treated in our hospital according to the modified pediatric protocol DAL-HD-90 in 1997–2007. QoL was assessed using the Short Form 36 (SF-36) which enabled generating 8 separate scales and 2 final scores (0 = worst possible health, 100 = best possible health). All survivors were in complete remission of HL for ³ 5 years.

Results. The HL survivors had the lower scores than the normal controls according to all scales and SF-36. Statistically significant differences were found in: general health — 53.4 (95 %CI 47.8–59.1) vs. 72.3 (68.8–75.8; < 0,001), vitality — 54.7 (50.4–59.1) vs. 72.2 (69.3–75.2; < 0.001), and mental health — 57.4 (53.5–61.4) vs. 71.7 (68.6–74.8; < 0.001). The patients at the age ³ 18.5 years (ROC-curves; = 0.047) at the time of HL diagnosis had poorer QoL when compared to younger patients with respect to: general health — 48.3 (41.3–55.2) vs. 60.9 (51.6–70.2; = 0.027): vitality — 50.3 (44.7–55.9) vs. 61.1 (51.6–70.2; = 0.013). The patients with the unfavorable events including relapse (n = 6) and second malignancy (n = 2) showed the lowest scores of QoL, especially in physical role performance [34.4 (2.6–71.3) vs. 79.7 (77.8–89.6; = 0.002)] and emotional role performance [25.0 (7.5–57.5) vs. 77.8 (67.1–88.4; < 0.001)]. Duration of remission, age at the QoL evaluation, gender, therapy intensity (2, 4, or 6 cycles of primary chemotherapy plus radiotherapy), Ann-Arbor stages, bulky disease, current married status, and education levels showed no significant influence on the QoL parameters.

Conclusion. Long-term HL survivors had poorer physical and mental QoL than the general population of young adults. The age at the time of LH diagnosis ³ 18.5 years was associated with significantly reduced QoL. The relapsed HL and second malignancies were mostly associated with the deterioration of physical and emotional role functioning that may indicate uncertainty of patients about future well-being.


Keywords: Hodgkin’s lymphoma, quality of life, adolescents, young adults, DAL-HD-90, SF-36

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REFERENCES

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

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

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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Rituximab (MabThera) for subcutaneous administration, new opportunities well-studied drug

G.S. Tumyan

N.N. Blokhin Russian Cancer Research Center of RAMS, Moscow, Russian Federation


ABSTRACT

The current concept of anticancer therapy optimization means reduction of health care costs, decreased toxicity with the same or greater efficacy of the administered drug, and, as the result, more comfortable and convenient management of cancer patients. The new formulation of Rituximab (Mabthera) for subcutaneous (SC) administration meets all above criteria. The clinical studies of this drug demonstrate non-inferiority of the fixed dose 1400 mg SC compared to the approved dose of 375 mg/m2 intravenously. Mabthera SC shows the safety profile similar to the formulation for intravenous administration and makes the delivery of the drug faster (mean SC injection time = 10 minutes), safer, and more convenient for patients.


Keywords: Mabthera, formulation for subcutaneous administration.

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