LYMPHOID TUMORS

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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  4. Salles G, Mounier N, de Guibert S, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008;112(13):4824–31. doi: 10.1182/blood-2008-04-153189.
  5. Hiddemann W, Kneba M, Dreyling M, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106(12):3725–32. doi: 10.1182/blood-2005-01-0016.
  6. Herold M, Haas A, Srock S, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007;25(15):1986–92. doi: 10.1200/JCO.2006.06.4618.
  7. Marcus R, Imrie K, Solal-Celigny P, et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008;26(28):4579–86. doi: 10.1200/JCO.2007.13.5376.
  8. Cartron G, Dacheux L, Salles G, et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor Fc gamma gene. Blood. 2002;99(3):754–8. doi: 10.1182/blood.V99.3.754.
  9. Van Meerten T, Van Rijn RS, Hol S, et al. Complement-induced cell death by rituximab depends on D20 expression level and acts complementary to antibody-dependent cellular cytotoxicity. Clin Cancer Res. 2006;12(13):4027–35. doi: 10.1158/1078-0432.CCR-06-0066.
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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.

Role of Superficial CD200 Marker in Differential Diagnosis of Malignant B-Cell Lymphoproliferative Diseases

LYMPHOID TUMORS , , , , ,

YuV Mirolyubova, EA Stadnik, TS Nikulina, VV Strugov, TO Andreeva, YuV Virts, RV Grozov, AYu Zaritskey

Federal Almazov North-West Medical Research Centre, 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, Nikulina TS, et al. Role of Superficial CD200 Marker in Differential Diagnosis of Malignant B-Cell Lymphoproliferative Diseases. Clinical oncohematology. 2017;10(2):169–75 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-169-175

ABSTRACT

Background & Aims. Flow cytometry is successfully used for diagnosis of malignant lymphoproliferative disorders. However, there are atypical cases that are difficult to interpret; thus, new markers relevant for the differential diagnosis are to be searched for. The aim is to analyze CD200 expression in patients with B-cell lymphoproliferative disorders.

Materials & Methods. 187 patients with chronic lymphocytic leukemia (CLL), 14 patients with mantle cell lymphoma (MCL), 9 patients with marginal zone lymphoma (MZL), and 5 patients with hairy cell leukemia (HCL) were enrolled in the study. Neoplasm was not confirmed in 12 subjects. The patients underwent the following tests: CBC, immunophenotyping of peripheral blood or bone marrow lymphocytes, and a cytogenetic test. In some cases, an additional immunohistochemical test of bone marrow trepanobiopsy or lymph node biopsy samples was required.

Results. In all cases of CLL and HCL, the CD200 expression was positive; mean fluorescence intensity was higher in these cases as compared to other groups. Negative expression of CD200 prevailed in MCL patients; however, at the same time 2 cases of intermediate and positive expression were reported, both showing moderate fluorescence intensity values. CD200 expression was heterogeneous in MZL patients.

Conclusion. The CD200 negative expression excludes typical HCL and CLL. Additional cytogenetic and immunnohistoсhemical tests should be performed in such cases to verify the diagnosis, first of all, MCL or MZL.

Keywords: CD200, flow cytometry, diagnosis, chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, hairy cell leukemia.

Received: September 7, 2016

Accepted: January 3, 2017

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REFERENCES

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  18. Kretz-Rommel A, Qin F, Dakappagari N, et al. CD200 expression on tumor cells suppresses antitumor immunity: new approaches to cancer immunotherapy. J Immunol. 2007;178(9):5595–605. doi: 10.4049/jimmunol.178.9.5595.
  19. Moreaux J, Hose D, Reme T, et al. CD200 is a new prognostic factor in multiple myeloma. Blood. 2006;108(13):4194–7. doi: 10.1182/blood-2006-06-029355.
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Evaluation of Minimal Residual Disease in B-Lineage Acute Lymphoblastic Leukemia Using EuroFlow Approaches

LYMPHOID TUMORS , ,

OA Beznos, LYu Grivtsova, AV Popa, MA Shervashidze, IN Serebryakova, OYu Baranova, EA Osmanov, NN Tupitsyn

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

For correspondence: Ol’ga Alekseevna Beznos, junior researcher, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: 8(916)480-03-35; e-mail: beznos.olga@gmail.com

For citation: Beznos OA, Grivtsova LYu, Popa AV, et al. Evaluation of Minimal Residual Disease in B-Lineage Acute Lymphoblastic Leukemia Using EuroFlow Approaches. Clinical oncohematology. 2017;10(2):158–68 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-158-168

ABSTRACT

Background & Aims. Evaluation of the minimal residual disease (MRD) at different stages of chemotherapy is one of key prognostic factors and a factor of stratification of patients into risk groups in acute lymphoblastic leukemia (ALL). The MRD detection on Day 15 and at later stages is based on identifying blast cells with a leukemia-associated immune phenotype. The aim is to assess the potential of 8-color standardized EuroFlow panels and to detect individual criteria for MRD monitoring during primary diagnosis.

Materials & Methods. The analysis included data on the primary immune phenotype and MRD assessment during chemotherapy in 10 adults and 35 children with a confirmed diagnosis of B-cell precursors ALL.

Results. The ALL phenotype characteristics at the stage of primary diagnosis permit to make the most complete description of the of 8-color standardized EuroFlow panels. This gives an opportunity to select the most informative antigen combinations for further MRD monitoring. Combinations with CD58/CD38, CD81/СD9 antigen expression, as well as assessment of pan-myeloid CD13, CD33 antigen co-expression may be recommended as the most frequent aberrant immune phenotypes of blast cells in ALL. As for B-lineage progenitor cells in children on Day 15 of the induction therapy, a detection of TdT+ сyCD22+ cell population is necessary in addition to the quantification of CD10+ and/or CD34+ В-lineage progenitor cells.

Conclusion. Therefore, the 8-color standardized EuroFlow panels permit not only to characterize the primary ALL immune phenotype in details, but may also be widely used for MRD evaluation at all stages of chemotherapy.

Keywords: B-lineage acute lymphoblastic leukemia, multicolor flow cytometry, minimal residual disease.

Received: January 14, 2017

Accepted: January 29, 2017

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REFERENCES

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    [Grivtsova LYu, Popa AV, Kupryshina NA, et al. Detection of minimal residual disease in children with B-cell precursor acute lymphoblastic leukemia with simplified protocols. Immunologiya gemopoeza. 2008;5(2):8–33. (In Russ)]
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    [Grivtsova LYu, Popa AV, Serebryakova IN, Tupitsyn NN. To further standardization in detection of residual blasts in bone marrow of children with B-cell acute lymphoblastic leukemia on Day 15 of induction therapy. Immunologiya gemopoeza. 2011;8(1):35–54. (In Russ)]
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Relevance of Positron-Emission Therapy for Optimization of Treatment of Advanced Hodgkin’s Lymphoma Using Intensive ЕАСОРР-14 Program

LYMPHOID TUMORS , ,

EA Demina1, AA Leont’eva1, GS Tumyan1, YuE Ryabukhina1, EG Medvedovskaya1, OP Trofimova1, VM Sotnikov2, VB Larionova1, EV Paramonova1, LV Manzyuk1, NV Kokosadze1, OV Mukhortova3, IP Aslanidi3, AYu Zaitseva4, LA Radkevich4, MS Rudas5, VA Manukova5, EA Osmanov1

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

2 Russian Scientific Center of Roentgenoradiology under the Ministry of Health of the Russian Federation, 86 bld. 5 Profsoyuznaya str., Moscow, Russian Federation, 117997

3 AN Bakulev Scientific Center for Cardiovascular Surgery, 8 bld. 7 Leninskii pr-t, Moscow, Russian Federation, 117931

4 Clinical Hospital No. 1 under the Administration of Presidential Affairs of the Russian Federation, 45 Losinoostrovskaya str., Moscow, Russian Federation, 107150

5 Central Clinical Hospital under the Administration of Presidential Affairs of the Russian Federation, 15 Marshala Timoshenko str., Moscow, Russian Federation, 121359

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, Leont’eva AA, Tumyan GS, et al. Relevance of Positron-Emission Therapy for Optimization of Treatment of Advanced Hodgkin’s Lymphoma Using Intensive ЕАСОРР-14 Program. Clinical oncohematology. 2017;10(2):150–7 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-150-157

ABSTRACT

Aim. To evaluate the relevance of the positron-emission therapy (PET) for optimization of the therapy of advanced Hodgkin’s lymphoma (HL) using the intensive EACOPP-14 program.

Materials & Methods. 91 patients with advanced HL (IIX–IIE, III–IV) received the treatment according to the “ЛХМосква1-3” protocol over the period from November 2009 to February 2015, and then the treatment was analyzed. The median age was 29 years (range: 17–50); there were 42 men (46.3 %) and 49 (53.7 %) women. The treatment included 6 cycles of polychemotherapy according to the regimen ЕА(50)СОРР-14 ± radiation therapy. The radiation therapy was performed in 66 patients (72.5 %) after the completion of the chemotherapy. The cumulative focal dose was 30 Gy onto the areas of residual lesions and/or initially large tumor masses.

Results. PET performed during the initial HL diagnosing permited to identify new areas of neoplastic lesions without changes in staging and treatment scheme, as well as specify areas and field size of planned radiation consolidation. The paper confirms the prognostic value of the intermediate PET in patients with advanced HL during the intensive first-line chemotherapy. The intensive therapy at the beginning of the treatment program is associated with higher chances for survival for patients with extremely unfavorable prognosis. After completion of the drug therapy, negative PET findings had a higher prognostic value, than the positive ones. The analysis of the relevance of residual tumor dimensions in the PET negative group demonstrated that the relapses were more common, if the residual tumor was more than 4.5 cm (according to CT findings).

Conclusion. This study confirmed that it reasonable to discuss the discontinuation of the radiation therapy in patients with advanced HL, negative PET findings and small (< 2.5 cm) residual tumor after the intensive ЕАСОРР-14 program. This tactics permits avoiding a number of delayed complications.

Keywords: Hodgkin’s lymphoma, advanced disease, intensive first-line therapy, PET.

Received: January 2, 2017

Accepted: January 14, 2017

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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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V(D)J Recombination Excision Circles of B- and T-cells as Prognostic Marker in B-Cell Chronic Lymphocytic Leukemia

LYMPHOID TUMORS , , , ,

IV Obraztsov1,2, MA Gordukova 3, NA Severina4, BV Biderman4, SYu Smirnova4, AB Sudarikov4, EA Nikitin5, AG Rumyantsev1

1 Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology under the Ministry of Health of the Russian Federation, 1 Samory Mashela str., Moscow, Russian Federation, 117198

2 AN Ryzhikh State Scientific Center for Coloproctology under the Ministry of Health of the Russian Federation, 2 Salyama Adilya str., Moscow, Russian Federation, 123423

3 GN Speranskii Municipal Children’s Hospital No. 9, 29 Shmitovskii pr-d, Moscow, Russian Federation, 123317

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

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

For correspondence: Igor’ Vladimirovich Obraztsov, junior researcher, 1 Samory Mashela str., Moscow, Russian Federation, 117997; е-mail: igor_obraztsov@yahoo.com

For citation: Obraztsov IV, Gordukova MA, Severina NA, et al. V(D)J Recombination Excision Circles of B- and T-cells as Prognostic Marker in B-Cell Chronic Lymphocytic Leukemia. Clinical oncohematology. 2017;10(2):131–40 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-131-140

ABSTRACT

Background & Aims. T-cell receptor excision circles (TREC) and κ-deleting recombination excision circles (KREC) are extrachromosomal DNA segments generated during V(D)J re combination process that characterize the diversity of the antigen repertoire of T- and B-cells. The aim of our study is to identify the prognostic value of the excision circles in the chronic lymphocytic leukemia (CLL) setting.

Methods. The excision circles’ levels were assessed by means of real time PCR in 109 patients with high-risk CLL and 16 matched healthy individuals.

Results. KREC levels were signifi cantly (p < 0.001) lower in CLL patients vs. the reference group. TREC levels were lower in groups with unmutated status of immunoglobulin heavy chain variable region genes (p < 0.05) and 11q deletions (p < 0.1). Moreover, the KREC levels were higher in NOTCH1 mutation carriers than in noncarriers (p < 0.05). The comparison of treatment outcomes demonstrated a correlation between a high TREC level and achievement of complete remission. The prognostic value of the biomarker was confirmed by ROC-analysis: AUCTREC = 0.713 (p = 0.001)

Conclusion. Association between excision circles’ levels and clinical/laboratory CLL prognostic factors, as well as complete remission achievement, makes possible the implementation of the test for early prediction of the treatment outcome.

Key words: CLL, TREC, KREC, naive T-cells, naive B-cells, biomarkers, outcome predictors.

Received: November 10, 2016

Accepted: January 13, 2017

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Features of Imaging of Different Types of Hodgkin’s Lymphoma Using Combined Positron Emission and Computed Tomography

LYMPHOID TUMORS , , ,

AS Subbotin1, NG Afanas’eva2

1 Chelyabinsk District Clinical Oncological Dispensary, 42 Blyukhera str., Chelyabinsk, Russian Federation, 454087

2 South Ural State Medical University, 64 Vorovskogo str., Chelyabinsk, Russian Federation, 454092

For correspondence: Aleksei Sergeevich Subbotin, 42 Blyukhera str., Chelyabinsk, Russian Federation, 454087; e-mail: acsubbotin@yandex.ru

For citation: Subbotin AS, Afanas’eva NG. Features of Imaging of Different Types of Hodgkin’s Lymphoma Using Combined Positron Emission and Computed Tomography. Clinical oncohematology. 2017;10(1):61–4(In Russ).

DOI: 10.21320/2500-2139-2017-10-1-61-64

ABSTRACT

Background & Aims. At present, PET-CT has an important clinical significance in Hodgkin’s lymphoma (HL) and is used both for initial tumor staging and restaging and for the evaluation of treatment efficacy. Published data indicate the possible lack of radiotracer accumulation in the tumor tissue in HL before primary treatment. A low metabolic activity of the tumor tissue prior to treatment makes it difficult to assess the treatment dynamics during the anti-tumor therapy. The aim of this work is to determine the incidence of the low metabolic activity of tumor tissue in HL.

Methods. Findings of 131 18F-fluorodeoxyglucose (FDG) whole body PET-CT scans of patients with histologically verified HL (over the period from 2011 to 2015) were studied retrospectively. Patterns of FDG accumulation in different histological types of HL, as well as the levels of metabolic activity in patients with tumor-related toxicity symptoms (B-symptoms) were studied.

Results. The low metabolic activity was detected in 4 % of patients with de novo HL. The highest levels of metabolic activity were detected in nodular sclerosis and the lowest ones in nodular lymphocyte-predominant HL. Higher levels of radiotracer metabolic activity were observed in patients with general symptoms.

Conclusion. In general, a high metabolic activity of the neoplasm is typical for HL. Primary staging before the treatment should be performed for a more accurate evaluation of dynamics of HL treatment outcomes, because in a number of cases a baseline low FDG accumulation in the neoplasm may imitate the absence of a viable tumor tissue in the affected lymph nodes at assessment of treatment results.

Keywords: Hodgkin’s lymphoma, histological types, PET-CT, 18F-fluorodeoxyglucose.

Received: August 25, 2016

Accepted: December 19, 2016

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REFERENCES

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

LYMPHOID TUMORS , , , , ,

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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Elotuzumab for Treatment of Multiple Myeloma (Literature Review)

LYMPHOID TUMORS , ,

OM Votyakova

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

For correspondence: Ol’ga Mikhailovna Votyakova, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-92-09; e-mail: omvtk@yandex.ru

For citation: Votyakova OM. Elotuzumab for Treatment of Multiple Myeloma (Literature Review). Clinical oncohematology. 2016;9(4):438–45 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-438-445

ABSTRACT

Chemotherapy has been the main treatment option for multiple myeloma for several decades. However, a considerable increase in the life expectancy was observed in multiple myeloma patients when thalidomide, bortezomib and lenalidomide had been introduced into clinical practice. Nevertheless, the disease remains incurable and there is an unmet need in fundamentally new treatment methods. Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets SLAMF7, an antigen belonging to the signaling lymphocytic activation molecule family, with its high expression detected on myeloma cells. This review presents the mechanism of action of elotuzumab, preclinical data and the main clinical studies of this monoclonal antibody.

Keywords: monoclonal antibodies, elotuzumab, clinical studies, multiple myeloma.

Received: May 25, 2016

Accepted: June 15, 2016

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Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region

LYMPHOID TUMORS , , , ,

VI Bakhtina1,2, IV Demko2, AN Narkevich2, DS Gushchin3

1 Regional Clinical Hospital, 3а Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

2 Professor VF Voyno-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

3 Norilsk Inter-District Hospital No. 1, Solnechnyi pr-d, 7a Norilsk, Russian Federation, 663300

For correspondence: Varvara Ivanovna Bakhtina, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022; Tel: +7(923)357-57-77; е-mail: doctor.gem@mail.ru

For citation: Bakhtina VI, Demko IV, Narkevich AN, Gushchin DS. Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region. Clinical oncohematology. 2016;9(4):413–419 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-413-419

ABSTRACT

Background & Aims. B-cellular chronic lymphocytic leukemia (CLL) is a disease with heterogeneous clinical manifestations and biological characteristics. The age of 70 % of patients is more than 65 years by the date of the diagnosis; most of them have several comorbidities. The aim of the study is to identify factors affecting the survival, as well as to determine causes of mortality in CLL patients (according to data from hematological hospitals of Krasnoyarsk Region).

Methods. In order to identify the most significant factors affecting the course and the outcome of CLL, a retrospective analysis of data on patients who died in hematological hospitals was carried out. 45 cases with the lethal outcome were registered within six years. All patients were under hematologist’s supervision after diagnosing the disease, and they were followed throughout the treatment period up to the lethal outcome.

Results. Тhe overall and progression-free survival depended, first of all, on the type of the first line therapy and its efficacy. The progression of the underlying disease and infectious complications became the main reason of the lethal outcome in CLL patients.

Conclusion. Most patients received ineffective treatment as first line therapy. The analysis of the comorbidities showed that a more effective chemotherapy could be performed with achievement of longer complete remissions.

Keywords: chronic lymphocytic leukemia, oncohematological diseases, comorbidities, survival, treatment.

Received: May 16, 2016

Accepted: June 17, 2016

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