primary mediastinal (thymic) large B-cell lymphoma

Listeria monocytogenes Meningitis in a Female Patient with Primary Mediastinal (Thymic) Large B-Cell Lymphoma: A Case Report

AUTOIMMUNE THROMBOCYTOPENIA

AM Pronina1, SV Zhuravleva1, GS Yunaev1, IZ Zavodnova1, IA Kurmukov2

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

2 AS Loginov Moscow Clinical Scientific Center, 89 Entuziastov sh., Moscow, Russian Federation, 111123

For correspondence: Ildar Anvarovich Kurmukov, MD, PhD, 89 Entuziastov sh., Moscow, Russian Federation, 111123; e-mail: kurmukovia@gmail.com

For citation: Pronina AM, Zhuravleva SV, Yunaev GS, et al. Listeria monocytogenes Meningitis in a Female Patient with Primary Mediastinal (Thymic) Large B-Cell Lymphoma: A Case Report. Clinical oncohematology. 2020;13(4):420–5. (In Russ).

DOI: 10.21320/2500-2139-2020-13-4-420-425

ABSTRACT

Listeriosis with severe clinical manifestations in the form of bacteraemia, sepsis, and meningitis/meningoencephalitis is a rare but a challenging issue of supportive care in oncohematology. Early diagnosis of listeriosis, as well as any other infection, is hampered by severe general manifestations of a malignant lymphoproliferative disorder or tumor complications and its treatment. In patients with pronounced decreased drug-induced immunity listeriosis is usually characterized as a rapidly developing and, as a rule, severe disease with high immediate mortality. The present article offers a case report of severe listeria infection in a female patient admitted to the intensive care unit for the treatment of primary mediastinal (thymic) large B-cell lymphoma with a large tumor mass in anterior mediastinum complicated by mediastinal and superior vena cava compression syndromes.

Keywords: primary mediastinal (thymic) large B-cell lymphoma, listeriosis, meningitis, supportive care.

Received: June 14, 2020

Accepted: September 17, 2020

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REFERENCES

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Treatment of Aggressive Non-Hodgkin’s Lymphomas in Pregnancy

AUTOIMMUNE THROMBOCYTOPENIA , ,

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: v.k.jana@mail.ru

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

ABSTRACT

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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REFERENCES

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Rearrangement of Immunoglobulin Genes in Tumor Cells of Patients with Primary Mediastinal (Thymic) Large B-Cell Lymphoma

LYMPHOID TUMORS , , ,

YaK Mangasarova, YuV Sidorova, AU Magomedova, BV Biderman, EE Nikulina, AB Sudarikov, AM Kovrigina, SK Kravchenko

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

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

For citation: Mangasarova YaK, Sidorova YuV, Magomedova AU. Rearrangement of Immunoglobulin Genes in Tumor Cells of Patients with Primary Mediastinal (Thymic) Large B-Cell Lymphoma. Clinical oncohematology. 2019;12(3):271–7 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-271-277

ABSTRACT

Background. Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a malignant tumor with large atypical lymphoid cells expressing post-germinal differentiation markers. Rearrangements of immunoglobulin genes in PMBCL are revealed in 30–65 % of cases. Immunoglobulin molecules, however, are expressed neither on the surface, nor in cytoplasm of tumor cells.

Aim. To assess cell clonality rate on the basis of rearrangements of immunoglobulin heavy/light chain genes; to determine rearrangement stability at the time of relapse development; to study the range of rearrangements and clonal relationship with primary tumor in metachronous development of mediastinal gray zone lymphoma.

Materials & Methods. The assessment of rearrangements of immunoglobulin heavy/light chain genes was based on molecular analysis of 29 primary tumor biopsies and 4 tissue samples with histologically and immunohistochemically verified relapses or metachronous lymphoma development.

Results. In 16 (55.2 %) out of 29 cases a rearrangement of immunoglobulin heavy chain genes was reported, in 7 (24.1 %) cases a rearrangement of light chain genes was identified, in 6 (20.7 %) cases no rearrangements of immunoglobulin heavy/light chain genes were found. On the basis of immunoglobulin gene analysis in 2 patients with early relapse a tumor clone was detected that was identical with the one identified at the onset of the disease. In 2 patients with complete remission a metachronous development of mediastinal gray zone lymphoma was reported, whereas molecular genetic analysis revealed a change/disappearance of initial clonal rearrangements of immunoglobulin genes.

Conclusion. Total detection rate of B-cell clonality in PMBCL was 79.3 %. Molecular genetic analysis confirmed that initial clonal rearrangements of immunoglobulin genes were preserved in early relapses, and invalidated tumor clonal relationship in a metachronous development of mediastinal gray zone lymphoma.

Keywords: primary mediastinal (thymic) large B-cell lymphoma, rearrangement of immunoglobulin heavy/light chain genes, polymerase chain reaction, metachronous development of lymphoma.

Received: November 2, 2018

Accepted: May 29, 2019

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REFERENCES

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  2. Мангасарова Я.К., Магомедова А.У., Ковригина А.М. и др. Первичная медиастинальная (тимическая) В-крупноклеточная лимфома: диагностика отдаленных экстрамедиастинальных поражений и возможности лечения. Клиническая онкогематология. 2018;11(3):220–6. doi: 21320/2500-2139-2018-11-3-220-226.

    [Mangasarova YaK, Magomedova AU, Kovrigina AM, et al. Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Diagnostics of Extramediastinal Lesions and Treatment Opportunities. Clinical oncohematology. 2018;11(3):220–6. doi: 10.21320/2500-2139-2018-11-3-220-226. (In Russ)]

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Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Experience in Treating 131 Patients at a National Medical Research Center in Russia

LYMPHOID TUMORS , ,

IZ Zavodnova, MYu Kichigina, EV Paramonova, YuE Ryabukhina, OA Kolomeitsev, OP Trofimova, NV Volkova, YuI Pryamikova, NV Kokosadze, GS Tumyan

NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Prof. Gayane Sergeevna Tumyan, MD, PhD, 23 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-98-29; e-mail: gaytum@mail.ru

For citation: Zavodnova IZ, Kichigina MYu, Paramonova EV, et al. Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Experience in Treating 131 Patients at a National Medical Research Center in Russia. Clinical oncohematology. 2019;12(1):59–67.

DOI: 10.21320/2500-2139-2019-12-1-59-67

ABSTRACT

Background. Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is one of the primary extranodal tumors and originates from B-cells of thymic medulla. This disease is characterized by specific immunomorphologic and genetic features which distinguish it from other malignant lymphoproliferative disorders with similar parameters. Standard PMBCL treatment consists of immunochemotherapy and subsequent radiotherapy of residual mediastinal tumor. The advantages of one immunochemotherapy regimens over the other in controlled studies have not been shown.

Aim. To study current approaches to chemoradiation in PMBCL patients with an attempt to individualize them focusing on various prognostic factors.

Materials & Methods. The data of 131 patients with newly diagnosed PMBCL were analyzed, all of them were treated at NN Blokhin National Medical Cancer Research Center in the period from 2000 to 2017. More than a half were women (58 %), median age was 30 years (range 16–70). At different historical periods PMBCL treatment was performed using different immunochemotherapy regimens: MACOP-B±R in 55 (42 %) patients, R-CHOP  in 40 (30.5  %) patients, and R-DA-EPOCH  in 36 (27.5 %) patients.

Results. In general, the treatment of all PMBCL patients (n = 131) appeared to be highly effective. The remission rate was 87 %, 3-year progression-free survival (PFS) and overall survival (OS) was 78 % and 88 %, respectively. With median follow-up of 37 months relapses and progression of the disease were detected in 17 (13 %) out of 131 patients within a period of 13 months after initiation of antitumor treatment. There was not a single case of late relapse. The treatment of relapsed patients was not effective: 12-month OS was not higher than 37 %. Intensive immunochemotherapy regimens (МАСОР-В±R, R-DA-EPOCH) do not differ in their effectiveness, but they have significant advantages over the standard R-CHOP regimen. The results of positron emission tomography (PET) considered to be an important prognostic factor in PMBCL treatment: 3-year PFS in the PET-negative group was 92 % vs. 26 % in the PET-positive group.

Conclusion. The optimal algorithm of PMBCL treatment was elaborated with consideration of clinical factors, immunochemotherapy programs, degrees of tumor regression, its metabolic activity, and radiotherapy method and irradiation area.

Keywords: primary mediastinal (thymic) large B-cell lymphoma, treatment algorithm, prognostic factors.

Received: October 19, 2018

Accepted: December 23, 2018

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Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Diagnostics of Extramediastinal Lesions and Treatment Opportunities

LYMPHOID TUMORS , ,

YaK Mangasarova, AU Magomedova, AM Kovrigina, IE Kostina, ES Nesterova, LG Gorenkova, AE Misyurina, OV Margolin, SK Kravchenko

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

For correspondence: Yana Konstantinovna Mangasarova, MD, PhD, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: v.k.jana@mail.ru.

For citation: Mangasarova YaK, Magomedova AU, Kovrigina AM, et al. Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Diagnostics of Extramediastinal Lesions and Treatment Opportunities. Clinical oncohematology. 2018;11(3):220–26.

DOI: 10.21320/2500-2139-2018-11-3-220-226

ABSTRACT

Background. Current diagnostic methods and the introduction of molecular investigations into clinical practice allow to improve the understanding of classical primary mediastinal (thymic) large B-cell lymphoma (PMBCL).

Aim. To investigate clinical characteristics of PMBCL patients with extramediastinal lesions.

Materials & Methods. The study was performed from 2007 to 2017 in the National Medical Hematology Research Center and included 157 PMBCL patients. The data of 16 (10.2 %; 4 men and 12 women) patients with extramediastinal lesions were analyzed; the median age was 27 years (range 23–69).

Results. The extramediastinal lesions were found in pancreas (6; 37.5 %), kidneys (5; 31.2 %), ovaries (3; 18.7 %), liver (3; 18.7 %), bone marrow (3; 18.7 %), and breasts (2; 12 %); the lesions in stomach, bones, soft tissues, spleen, adrenals, and small pelvis were observed each in a single case. In 15 of 16 cases extramediastinal lesions were accompanied by involvement of superior mediastinum, and only 1 patient had an isolated lesion in thoracic soft tissues without mediastinal involvement. The samples of 8 out of 16 patients were analyzed using PCR. In all samples overexpression of 2 or more genes (JAK2, TRAF1, MAL, PDL1, PDL2) was determined which allowed to confirm, and in some cases to revise the diagnosis of PMBCL. Overall 5-year survival (93 %) of patients with classical PMBCL with thoracic involvement was similar to the cohort with extramediastinal lesions. All unfavourable events (progression/relapse) were identified at an early stage, i.e. within a year after the completion of therapy.

Conclusion. PMBCL patients can have not only superior mediastinum involvement, but extramediastinal lesions as well, including bone marrow. The spreading of the disease beyond superior mediastinum should be differentiated from diffuse large B-cell lymphoma using standard evaluation methods, and molecular analysis in some cases.

Keywords: primary mediastinal (thymic) large B-cell lymphoma, extramediastinal lesions, bone marrow involvement.

Received: January 22, 2018

Accepted: April 15, 2018

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

LYMPHOID TUMORS , , , , , ,

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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Primary Mediastinal (Thymic) Large B-Cell Lymphoma

REVIEWS , , , , , ,

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

LYMPHOID TUMORS , , , , , ,

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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