Characteristics of Hematopoiesis in Follicular Lymphoma Patients

MA Frenkel, AV Mozhenkova, NA Kupryshina, NA Falaleeva, NN Tupitsyn

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

For correspondence: Prof. Marina Abramovna Frenkel, MD, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-45-60; e-mail: marinafren@yandex.ru

For citation: Frenkel MA, Mozhenkova AV, Kupryshina NA, et al. Characteristics of Hematopoiesis in Follicular Lymphoma Patients. Clinical oncohematology. 2020;13(1):50–57 (In Russ).

DOI: 10.21320/2500-2139-2020-13-1-50-57


ABSTRACT

Aim. To assess hematopoiesis in follicular lymphoma (FL) patients at different disease stages with different morphologic structures of tumor and bone marrow microenvironment.

Materials & Methods. The trial included 152 FL patients treated from 2006 to 2016. In all of them the diagnosis was based on immunohistochemical analysis of extramedullar tumor as well as the analysis of bone marrow aspirates and core biopsy samples. In cases of bone marrow lesions (n = 33) a detailed morpho-immunophenotypic evaluation of tumor cells was carried out by means of flow cytometry, and lymphocyte subset panel evaluation was performed.

Results. Anemia, thrombocytopenia, and monocytosis in blood of FL patients are not associated with bone marrow lesions. In the absence of signs of these lesions anemia was detected in 23 (19 %) patients, thrombocytopenia was identified in 8 (7 %) patients, and 11 (9.1 %) patients showed monocytosis. Among patients with bone marrow lesions 9 (27.2 %) anemia, 11 (33.8 %) thrombocytopenia, and 7 (21 %) monocytosis cases were reported. Depth of cytopenia was determined by the degree of bone marrow tumor infiltration. Based on lymphocyte subset panel evaluation the following types of tumor cells in bone marrow aspirates were characterized: elements with blastic structure of nuclear chromatin, atypical lymphoid cells, and those similar to normal lymphocytes. Immunophenotypic heterogeneity of tumor cells in bone marrow was demonstrated. The trial showed that hemoglobin level, the count of blood thrombocytes and monocytes as well as the count of bone marrow T-cells are not associated with types of tumor cells.

Conclusion. Arrest of hematopoiesis and increasing number of monocytes in blood correlate with the degree of bone marrow tumor infiltration and are not affected by morphoimmunological characteristics of FL tumor cells.

Keywords: follicular lymphoma, centrocyte, centroblast, aspirate, core biopsy sample, immunophenotype.

Received: February 8, 2019

Accepted: December 2, 2019

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Prognostic Value of PRAME Activity in Tumor Cells of Follicular Lymphoma

VA Misyurin1, AE Misyurina2, SK Kravchenko2, NA Lyzhko1, YuP Finashutina1, NN Kasatkina1, DS Mar’in2, ES Nesterova2, NN Sharkunov3, MA Baryshnikova1, AV Misyurin1

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

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

3 SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

For correspondence: Vsevolod Andreevich Misyurin, PhD in Biology, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

For citation: Misyurin VA, Misyurina AE, Kravchenko SK, et al. Prognostic Value of PRAME Activity in Tumor Cells of Follicular Lymphoma. Clinical oncohematology. 2019;12(2):173–8.

DOI: 10.21320/2500-2139-2019-12-2-173-178


ABSTRACT

Aim. To set survival parameters for follicular lymphoma (FL) patients with different PRAME expression levels in tumor cells.

Materials & Methods. The study was conducted on samples of lymph nodes, blood, and bone marrow of 34 patients with newly diagnosed FL. PRAME expression levels were measured in tumor cells (centrocytes and centroblasts) by quantitative real-time PCR. The impact of different PRAME expression levels on survival parameters was studied with median follow-up of 29 months. Clinical and laboratory characteristics used for FLIPI-1 and FLIPI-2 calculations in different patient groups were compared.

Results. A high (> 5 % against ABL control gene) PRAME expression level correlates with higher Ki-67 activity (= 0.043) and larger tumor mass (= 0.04). Survival parameters were worse with high PRAME expression level in FL cells. Combination of both high FLIPI-1/FLIPI-2 risk and high PRAME expression level determines extremely unfavorable prognosis and may result in death.

Conclusion. In FL patients high PRAME expression level in tumor cells has negative prognostic value, but only in the presence of parameters determining high FLIPI-1 and FLIPI-2 risk. Juxtaposition of PRAME expression level and FLIPI-1/FLIPI-2 values enables most reliable prediction of early mortality in FL patients.

Keywords: PRAME gene, follicular lymphoma.

Received: November 4, 2018

Accepted: February 24, 2019

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

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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  13. Clarke LE, Bayerl MG, Ehmann WC, Helm KF. Cutaneous B-cell lymphoma with loss of CD20 immunoreactivity after rituximab therapy. J Cutan Pathol. 2003;30(7):459–62. doi: 10.1034/j.1600-0560.2003.00078.x.
  14. Hiraga J, Tomita A, Sugimoto T, et al. Down-regulation of CD20 expression in B-cell lymphoma cells after treatment with rituximab-containing combination chemotherapies: its prevalence and clinical significance. Blood. 2009;113(20):4885–93. doi: 10.1182/blood-2008-08-175208.
  15. Davis TA, Czerwinski DK, Levy R. Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression. Clin Cancer Res. 1999;5(3):611–5.
  16. Alvaro-Naranjo T, Jaen-Martinez J, Guma-Padro J, et al. CD20-negative DLBCL transformation after rituximab treatment in follicular lymphoma: a new case report and review of the literature. Ann Hematol. 2003;82(9):585–8. doi: 10.1007/s00277-003-0694-1.
  17. Matsuda I, Hirota S. Bone marrow infiltration of CD20-negative follicular lymphoma after rituximab therapy: a histological mimicker of hematogones and B-cell acute lymphoblastic leukemia/lymphoma. Int J Clin Exp Pathol. 2015;8(8):9737–41.
  18. Kennedy GA, Tey SK, Cobcroft R, et al. Incidence and nature of CD20-negative relapses following rituximab therapy in aggressive B-cell non-Hodgkin’s lymphoma: a retrospective review. Br J Haematol. 2002;119(2):412–6. doi: 10.1046/j.1365-2141.2002.03843.x.

Diagnosis of Pediatric-Type Follicular Lymphoma in Young Adults (Own Data)

AM Kovrigina, LV Plastinina, SK Kravchenko, ES Nesterova, TN Obukhova

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

For correspondence: Alla Mikhailovna Kovrigina, DSci, Professor, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel: +7(495)612-62-12; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM, Plastinina LV, Kravchenko SK, et al. Diagnosis of Pediatric-Type Follicular Lymphoma in Young Adults (Own Data). Clinical oncohematology. 2017;10(1):52–60 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-52-60


ABSTRACT

Aim. Pathomorphological, immunophenotypical and clinical characteristics of a new clinico-morphological form of pediatric-type follicular lymphoma (FL) in young adults discovered in 2008 (WHO classification).

Background. FL is a heterogeneous disease according to its morphological, immunophenotypical and molecular-genetic characteristics. FL de novo includes transformed FL, FL without t(14;18), FL with diffuse growth associated with del(1p.36) and TNFRSF14 mutation. Pediatric-type FL in young adults is poorly studied; and it is especially interesting because of its clinical diversity and molecular-genetic heterogeneity of FL, in general.

Methods. Biopsy materials taken from 5 patients (aged 18–25 years; median age: 22 years; the female/male ratio 3:2) were included in the study; all patients were examined, diagnosed and treated in the Hematology Research Center over the period from 2012 to 2016. Clinical stage I with isolated involvement a palatine tonsil or an inguinal lymph node was diagnosed in 4/5 patients; clinical stage II with involvement of a palatine tonsil and cervical lymph node was diagnosed in 1/5 patients. Morphological, immunophenotypical and FISH tests were performed with paraffin blocks.

Results. The morphological pattern was typical for FL 3B (n = 2) and FL 3 with blastoid nucleus morphology (n = 3). Immunophenotypical features demonstrated an intermediate position between FL 3 de novo and transformed FL 3. No BCL-2 rearrangement was detected in any observation.

Conclusion. The comparison of our data on characteristics of pediatric-type FL with those published in the literature demonstrated that lack or weak expression (< 30 % of tumor substrate cells) of MUM1 was the key feature of the experimental group of young adults with pediatric-type FL. This, in turn, indicates the absence of IRF4 rearrangements and possible presence of other genetic abnormalities. The clinical, morphological, and immunophenotypical characteristics broaden the FL heterogeneity spectrum in young adults.

Keywords: pediatric-type follicular lymphoma, follicular lymphoma, young adults, pathomorphology, immunohictochemistry, MUM1.

Received: August 14, 2016

Accepted: November 27, 2016

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High-Dose Chemotherapy for Grade 3B Relapsed Follicular Lymphoma with Deletions of Loci of BCL6 (3q27) and TP53 (17p13) Genes: Case Report and Literature Review

EE Zvonkov, NG Gabeeva, MV Firsova, EV Moiseeva, VV Troitskaya, LA Kuz’mina, TN Obukhova, AM Kovrigina, EN Parovichnikova, VG Savchenko

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

For correspondence: Nelli Georgievna Gabeeva, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-48-10; e-mail: dr.gabeeva@gmail.com

For citation: Zvonkov EE, Gabeeva NG, Firsova MV, et al. High-Dose Chemotherapy for Relapsed Follicular Lymphoma Grade 3B with Deletions of Loci of BCL6 (3q27) and TP53 (17p13) Genes: Case Report and Literature Review. Clinical oncohematology. 2015;8(1):36–43 (In Russ).


ABSTRACT

Background. The article describes a rare case of grade 3В follicular lymphoma (FL) with a nodular-diffuse growth; it also presents a literature review. Grade 3В follicular lymphoma with a nodular-diffuse growth is a rare lymphoid neoplasm, and no optimal therapeutic strategies have been developed for it. In addition to the absence of the classic t(14;18), combined deletions of 17p13 (TР53 gene locus) and 3q27 (BCL6 gene locus) are observed in a very few cases. This combination may negatively affect the FL prognosis. The unique ability of bendamustine to induce ТР53-independent apoptosis offers new opportunities for the high-dose chemotherapy of lymphomas.

Objective. To evaluate efficacy and tolerance of the ВеЕАМ conditioning regimen using high-dose bendamustine followed by autologous HSCT in a patient with 3B FL relapse and combined 17p13 and 3q27 deletion.

Methods. A 58-year-old man was diagnosed with 3B grade FL. After 8 R-CHOP courses and a two-year maintenance therapy with Rituximab, he developed a generalized enlargement of lymph nodes, and a neoplasm in left liver lobe. A liver biopsy confirmed the relapse of grade 3B FL with a nodular-diffuse growth and a high Ki-67 level (60 %). Cytogenetic analysis identified 17p13 and 3q27 deletions.

Results. Four courses of anti-relapse therapy were performed (2 — DHAP and 2 — ICE). PET scanning showed a complete regression in lymph nodes, whereas the size of the focus in the liver and the rate of accumulation of radiopharmaceuticals in it remained unchanged. ВеЕАМ conditioning regimen (bendamustine 600 mg) followed by autologous HSCT were performed. 46 days after the autologous HSCT, the tumor focus in the liver was PET-negative. The remission retained for 10 months.

Conclusions. Further study of the efficacy of high-dose bendamustine in the therapy of aggressive lymphoid tumors with TP53 mutation seems promising.


Keywords: follicular lymphoma, TP53-independent apoptosis, bendamustine.

Received: October 24, 2014

Accepted: October 27, 2014

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Follicular lymphoma: current trends and my choice

G.S. Tumyan

FSBI «N.N. Blokhin Russian Cancer Research Center» RAMS, Moscow, Russian Federation


ABSTRACT

In this first publication in the series «My Choice», we summarize recent data on the diagnosis and treatment of follicular lymphoma and suggest an algorithm of diagnostic and therapeutic measures, which allows a hematologist to individualize treatment for untreated and relapse patients. We discuss determination of «tumor burden» criteria and disease transformation and review variants of follicular lymphoma.


Keywords: follicular lymphoma, treatment.

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