rituximab

A Case of M-Paraprotein-Associated Polyneuropathy with Stable Response to Rituximab Therapy

RARE HEMATOLOGICAL TUMORS AND SYNDROMES , , ,

VG Potapenko1,3, VN Kiselev2

1 Municipal Clinical Hospital No. 31, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110

2 AM Nikiforov Russian Center of Emergency and Radiation Medicine, 4/2 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

3 IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Vsevolod Gennad’evich Potapenko, 3 Dinamo pr-t, Saint Petersburg, Russian Federation, 197110; Tel.: +7(905)284-51-38; e-mail: potapenko.vsevolod@mail.ru

For citation: Potapenko VG, Kiselev VN. A Case of M-Paraprotein-Associated Polyneuropathy with Stable Response to Rituximab Therapy. Clinical oncohematology. 2019;12(4):434–7 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-434-437

ABSTRACT

Monoclonal gammopathy of undetermined significance is diagnosed on the basis of an extensive search for a diagnostic reason as paraprotein secretion occurs in different diseases. One of polyneuropathies associated with M-paraproteinemia is anti-MAG demyelinating polyneuropathy (AMDP). The first-line treatment of this disease is based on prednisolone, and intravenous immunoglobulin. The second-line therapy of treatment-resistant patients is not determined. We report a case of a female patient with AMDP who received prednisolone, azathioprine, and plasmapheresis; however, stable response was reached only after the use of rituximab.

Keywords: paraprotein, monoclonal gammopathy of undetermined significance (MGUS), myelin-associated glycoprotein (MAG), polyneuropathy, rituximab.

Received: January 22, 2019

Accepted: September 5, 2019

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REFERENCES

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  13. Edwards JC, Szczepanski L, Szechinski J, et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N Engl J Med. 2004;350(25):2572–81. doi: 10.1056/nejmoa032534.

Effectiveness of the Initial Escalation of Immunochemotherapy in Patients with High Risk MALT-Lymphoma: Pilot Study Results

LYMPHOID TUMORS , , , , ,

AK Smol’yaninova, NG Gabeeva, SA Tatarnikova, AV Belyaeva, AM Kovrigina, EG Gemdzhyan, EE Zvonkov

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

For correspondence: Anna Konstantinovna Smol’yaninova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-48-10; e-mail: annmo8@mail.ru.

For citation: Smol’yaninova AK, Gabeeva NG, Tatarnikova SA, et al. Effectiveness of the Initial Escalation of Immunochemotherapy in Patients with High Risk MALT-Lymphoma: Pilot Study Results. Clinical oncohematology. 2018;11(4):338–48.

DOI: 10.21320/2500-2139-2018-11-4-338-348

ABSTRACT

Background. MALT-lymphoma is usually characterized with an indolent course. The factors underlying the effectiveness of the standard chemotherapy in patients with MALT-lymphomas include MALT-IPI risk group and a high SUVmax according to the results of positron emission tomography (PET). All well-known MALT-lymphoma risk factors indirectly indicate a high risk of transformation to large cell lymphoma. The search for an effective chemotherapy continues.

Aim. To evaluate the effectiveness of the R-EPOCH/R-BAC escalated immunochemotherapy for MALT-lymphoma patients with poor prognosis factors.

Materials & Methods. In the period of 2016–2017 the study included 5 female MALT-lymphoma patients (the mean age of 41 years), of which 1 patient had an early relapse after surgery and 4 patients were newly diagnosed. Prior to therapy 4 patients were evaluated with PET. The mean SUVmax was 10.04. According to MALT-IPI 2 patients belonged to a high-risk group and 3 belonged to a middle-risk group. All the patients received R-EPOCH/R-BAC regimen therapy. A month after completing the treatment all the patients were again evaluated with PET.

Results. In 4 patients with 10–24 months follow-up complete remission was reported, which was confirmed by the results of histology and PET. The treatment of 1 patient was not completed. The immunotherapy was well tolerated by the patients. Hematological toxicity grade 3–4 occurred only after completing R-BAC treatment regimens. No severe infectious complications were reported.

Conclusion. MALT-lymphoma patients need to be evaluated in terms of all prognostic factors to identify the high-risk patients for whom escalated therapy is to be used already in the first line treatment. This pilot study of the use of R-EPOCH/R-BAC for treatment of MALT-lymphoma patients with poor prognosis factors yielded positive results and showed its acceptable tolerance.

Keywords: MALT-lymphoma, immunochemotherapy, positron emission tomography, prognosis factors, rituximab, ribomustin, cytarabine.

Received: April 10, 2018

Accepted: August 3, 2018

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Minimal Residual Disease and IGHV-Genes Mutational Status as the Main Predictors of Response to Bendamustine-Rituximab Therapy in Previously Untreated Chronic Lymphocytic Leukemia

LYMPHOID TUMORS , , , , , ,

YuV Mirolyubova, EA Stadnik, VV Strugov, TO Andreeva, TS Nikulina, YuV Virts, PA Butylin, AG Rumyantsev, AYu Zaritskey

VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

For correspondence: Yuliya Vladimirovna Mirolyubova, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; e-mail: juli9702@yandex.ru

For citation: Mirolyubova YuV, Stadnik EA, Strugov VV, et al. Minimal Residual Disease and IGHV-Genes Mutational Status as the Main Predictors of Response to Bendamustine-Rituximab Therapy in Previously Untreated Chronic Lymphocytic Leukemia. Clinical oncohematology. 2018;11(2):167–74.

DOI: 10.21320/2500-2139-2018-11-2-167-174

ABSTRACT

Background. In patients with chronic lymphocytic leukemia (CLL) the eradication of minimal residual disease (MRD) is a prognostic factor of overall survival (OS) and progression-free survival (PFS). IGHV mutational status has also independent prognostic value.

Aim. To analyse the impact of mutational status and MRD eradication in CLL patients after first-line standard BR (bendamustine + rituximab) immunochemotherapy.

Materials & Methods. The prospective study included patients with immunophenotypically confirmed CLL who had not previously received anticancer therapy. All patients were treated by BR combination from 2012 to 2015. MRD level was determined in 109 patients after completing the 3rd and the 6th treatment courses. IGHV mutational status data were available for 98 patients. IGHV mutational status was evaluated in accordance with ERIC recommendations. MRD was assessed by standardized method of 4-color flow cytometry.

Results. MRD negativity was achieved in 37 (34 %) out of 109 patients. MRD eradication correlated with the best PFS (p = 0.04). IGHV mutational status had a statistically significant impact on PFS (p = 0.02). In patients with MRD-negative response and IGHV mutation no unfavorable events occurred during the period of monitoring. Conversely, PFS rates in MRD-negative patients having no IGHV mutation and in MRD-positive patients with mutation were significantly worse. MRD eradication resulted in statistically significant improvement of PFS rates after completing 3 treatment courses, compared with the cases with MRD persistence regardless of residual malignant clone level (p = 0.01).

Conclusion. BR therapy as first-line treatment statistically improved PFS in patients who achieved MRD-negative remission after completing the 3rd treatment course. PFS was significantly higher in MRD-negative patients with IGHV mutation after 6 treatment courses. MRD negativity resulting from 6 BR therapies in patients having no IGHV mutation was not accompanied by PFS improvement. It follows that by itself MRD negativity cannot be considered to be a universal prognostic factor.

Keywords: chronic lymphocytic leukemia, minimal residual disease, bendamustine, rituximab, BR, IGHV, mutational status.

Received: December 29, 2017

Accepted: February 27, 2018

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Effect of Patients’ Endocrine Status on Effectiveness of Treatment with Rituximab: State of the Art

LYMPHOID TUMORS , , , ,

YuV Komoza1, VA Komoza1, SV Chernavskii2, OA Rukavitsyn2

1 Bryansk Regional Oncology Dispensary, 96 Stanke Dimitrova pr-t, Bryansk, Russian Federation, 241033

2 Academician NN Burdenko Principal Military Clinical Hospital under the Ministry of Defence of the Russian Federation, 3 Gospital’naya pl., Moscow, Russian Federation, 105229

For correspondence: Yuliya Valer’evna Komoza, 96 Stanke Dimitrova pr-t, Bryansk, Russian Federation, 241033; e-mail: smile-32@mail.ru

For citation: Komoza YuV, Komoza VA, Chernavskii SV, Rukavitsyn OA. Effect of Patients’ Endocrine Status on Effectiveness of Treatment with Rituximab: State of the Art. Clinical oncohematology. 2017;10(2):187–90 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-187-190

ABSTRACT

The non-Hodgkin’s lymphoma morbidity rate is gradually increasing, and its peak is registered in patients aged 45–60 years. At the same time, the world population steadily becomes older. Monoclonal antibodies (Rituximab) have been used in the treatment of patients with CD20-positive lymphomas for more than 20 years. The use of this drug enhanced the effectiveness of the therapy significantly. However, when patients were divided into groups by age and sex, better results were obtained in the group of women over 60 years. The review presents the results of several studies which have analyzed the effectiveness of rituximab-based schemes in patients depending on their sex and age, using different dosages and administration regimens. The article also presents our personal conclusions about the possible causes of the differences in efficacy of the drug in some patient populations. Identification of the causes contributing to the improvement of the effectiveness of rituximab in elderly women may significantly change approaches to the treatment of lymphomas in patients of both sexes.

Keywords: non-Hodgkin’s lymphoma, rituximab, lymphoma therapy effectiveness, gender differences, age differences.

Received: November 30, 2016

Accepted: January 17, 2017

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Loss of CD20 Expression in Follicular Lymphoma after Program Anti-Tumor Therapy Including Rituximab: Literature Data and Case Report

LYMPHOID TUMORS , ,

OM Volodina, NA Kupryshina, NA Falaleeva, VA Doronin, AV Mozhenkova, MA Frenkel’, EN Sorokin, NV Kokosadze, NN Tupitsyn, GS Tumyan, EA Osmanov

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

For correspondence: Ol’ga Mikhailovna Volodina, post-graduate student, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-28-54; e-mail: volodi.olga2012@yandex.ru.

For citation: Volodina OM, Kupryshina NA, Falaleeva NA, et al. Loss of CD20 Expression in Follicular Lymphoma after Program Anti-Tumor Therapy Including Rituximab: Literature Data and Case Report. Clinical oncohematology. 2017;10(2):176–81 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-176-181

ABSTRACT

It is the first description of a case of follicular lymphoma with a loss of CD20 antigen expression during the anti-tumor treatment including rituximab in the NN Blokhin Russian Cancer Research Center. The article discusses the tactics of further management of such patients and the effect of the CD20-negative status of follicular lymphoma tumor cells acquired during immunochemotherapy.

Keywords: follicular lymphoma, CD20-negative, rituximab.

Received: November 18, 2016

Accepted: February 2, 2017

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REFERENCES

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Effect of IGHV Gene Mutation Status and BCR Structure Stereotypy on Effectiveness of BR Regimen in First-Line Therapy of Chronic Lymphocytic Leukemia

LYMPHOID TUMORS , , , , , , ,

VV Strugov1, EA Stadnik1,2, AM Rumyantsev1, TO Andreeva1, YuV Virts1, YuV Mirolyubova1, PA Butylin1, AYu Zaritskey1,2

1 Federal Almazov North-West Medical Research Centre, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

2 Internal medicine clinic, Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Vladimir Vladimirovich Strugov, staff scientist, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel: +7(812)702-37-49; e-mail: strugov@almazovcentre.ru

For citation: Strugov VV, Stadnik EA, Rumyantsev AM, et al. Effect of IGHV Gene Mutation Status and BCR Structure Stereotypy on Effectiveness of BR Regimen in First-Line Therapy of Chronic Lymphocytic Leukemia. Clinical oncohematology. 2017;10(2):141–9 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-141-149

ABSTRACT

Background & Aims. The IGHV gene mutation status is a constant biological feature of tumor cells in chronic lymphocytic leukemia (CLL). This parameter is an important predictor of the efficacy of immunochemotherapy. It was included into the CLL international prognostic index CLL-IPI developed recently. The aim is to evaluate the prognostic significance of the BR regimen in patients with different variants of the B-cell receptor (BCR) structure.

Methods. The study examined immediate and delayed treatment outcomes for 183 CLL patients included in a Russian, prospective, observational BEN-001 trial (NCT02110394). The median age was 61 years (range: 35–79); 53/179 (29.6 %) patients were older than 65; and 14/179 (7.8 %) patients were older than 75. Prevalence of males (110/179, 61.5 %) in the male/female ratio (1.6:1.0) was observed. Most patients had advanced disease: Binet B 116/173 (67 %) or Binet C 38/173 (22 %). The patients received the first-line therapy according to the BR regimen at standard doses in 36 hematological institutions in the Russian Federation over the period from 2012 until 2015. The genome DNA isolated from mononuclear leukocytes in the peripheral blood was used to assess the mutation status of the IGHV-genes.

Results. The study demonstrated that unmutated CLL (≥ 98 % of homology to germline gene) is associated with worsening of the event-free and overall survival rates most of all; at that, the complete remission rate and the MRD-free survival rate were the same.

Conclusion. It is reasonable to analyze the IGHV mutation status in all patients prescribed with the BR regimen as the first-line therapy.

Keywords: chronic lymphocytic leukemia, CLL, bendamustine, rituximab, BR, IGHV, mutation status, stereotypy.

Received: January 8, 2017

Accepted: January 26, 2017

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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

COMPLICATIONS OF ANTITUMOR TREATMENT , , , , ,

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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Monoclonal Antibodies: from Development to Clinical Application

REVIEWS , ,

YuI Budchanov

Tver’ Medical University, 4 Sovetskaya str., Tver’, Russian Federation, 170000

For correspondence: Yurii Ivanovich Budchanov, 3 1st per. Krasnoi Slobody, Tver’, Russian Federation, 170001; e-mail: budjur@mail.ru

For citation: Budchanov YuI. Monoclonal Antibodies: from Development to Clinical Application. Clinical oncohematology. 2016;9(3):237-44 (In Russ).

DOI: 10.21320/2500-2139-2016-9-3-237-244

ABSTRACT

The development of monoclonal antibodies (MABs) resulted in revolutionary achievements in diagnosing and treating of oncohematological disorders. The review dwells on the history of the development and improved technologies for production of monoclonal antibodies illustrated by anti-CD20-MABs which recognize different epitopes of the CD20 antigens and have a higher antitumor activity. Engineering techniques can contribute to understanding the effector mechanisms of the application of the novel anti-CD20-MABs and are intended for further improvement of the treatment results.

Keywords: monoclonal antibodies, rituximab, ofatumumab, obinutuzumab, hybridoma technology.

Received: January 13, 2016

Accepted: March 17, 2016

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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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