LYMPHOID TUMORS

Chronic Lymphocytic Leukemia: Prognostic Significance of Minimal Residual Disease and Potential of Modern Methods of Its Diagnosis and Therapy (Literature Review)

LYMPHOID TUMORS , ,

AYu Kuvshinov, SV Voloshin, IS Martynkevich, EV Kleina, MA Mikhaleva, KM Abdulkadyrov

Russian Scientific Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Sergei Vladimirovich Voloshin, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)274-37-70; e-mail: kuvshinovmd@gmail.com

For citation: Kuvshinov AYu, Voloshin SV, Martynkevich IS, et al. Chronic Lymphocytic Leukemia: Prognostic Significance of Minimal Residual Disease and Potential of Modern Methods of Its Diagnosis and Therapy (Literature Review). Clinical oncohematology. 2016;9(2):191–8 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-191-198

ABSTRACT

Achieving a complete remission (CR) in patients with chronic lymphocytic leukemia (CLL) has become a feasible goal directly correlating with a prolonged survival. However, a certain number of tumor cells may be present in the patient’s body even when CR has been achieved, and this phenomenon is called a minimal residual disease (MRD). A lot of data confirming the necessity of MRD diagnosing and monitoring has emerged recently, since the MRD has a significant impact on the prognosis of CLL. Achieving MRD-negative remission is an independent predictor of long-term progression-free survival and overall survival. The occurrence of new diagnostic techniques has allowed to define the MRD and to develop standards for its assessment. This paper presents an overview of literature data about MRD, methods of its evaluation, prognostic significance, as well as the methods of eradication.

Keywords: chronic lymphocytic leukemia, minimal residual disease, flow cytometry.

Received: January 5, 2016

Accepted: January 10, 2016

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Role of Defects of Hematopoietic and Lymphoid Niches in Genesis of Chronic Lymphocytic Leukemia

LYMPHOID TUMORS , , , , ,

NYu Semenova, SS Bessmel’tsev, VI Rugal’

Russian Scientific Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Natal’ya Yur’evna Semenova, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-09-95; e-mail: sciencerugal@gmail.com

For citation: Semenova NYu, Bessmel’tsev SS, Rugal’ VI. Role of Defects of Hematopoietic and Lymphoid Niches in Genesis of Chronic Lymphocytic Leukemia. Clinical oncohematology. 2016;9(2):176–90 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-176-190

ABSTRACT

Background & Aims. Niche-forming elements of the bone marrow and lymphoid organs play an important role in the pathogenesis of chronic lymphocytic leukemias. The aim is to determine multifunctional characteristics of stromal elements of the hematopoietic and lymphoid microenvironment involved in formation of a niche of hematopoietic stem cells and lymphoid precursor cells.

Methods. Histological specimens of the bone marrow and lymph nodes of 112 CLL patients (64 men and 48 women) were investigated. 45 patients were included in the combined analysis group. The age median was 60 years. 50 volunteers were included in the control group: trepanobiopsy of the iliac area was performed in 30 healthy subjects, and lymph node biopsy was performed in 20 patients with reactive lymphadenopathy. Standard staining (hematoxylin-eosin, azure-II-eosin, silver impregnation, Masson stain) was used for histological studies. The immunohistochemical analysis was performed using the primary antibody panel and the polymer visualization system Dako according to staining protocol.

Results. While analyzing 96 trepanobioptates, we isolated three types of bone marrow infiltration: nodular (18.8 %, n = 18), interstitial (27 %, n = 26) and diffuse (54.2 %, n = 52). Nodular and interstitial bone marrow infiltrations reflect a more favorable course of CLL as compared to the diffuse type. The morphological characteristics of the bone marrow stroma of CLL patients may be caused by both primary impairment of the hematopoietic microenvironment, and cytokine disbalance resulting from the effect on the stroma of the leukemic clone. The morphological examination of lymph node bioptate of CLL patients demonstrated impairment of histoarchitectonics of lymphoid tissue elements in all cases. In lymph nodes of CLL patients, we demonstrated the increased number of small vessels on the background of decreased expression of extracellular matrix protein expression: IV type collagen, laminin, and desmin. Disintegration of lymph node follicular dendritic cells network was demonstrated.

Conclusion. Examination of the nature of the effect of stroma on hematopoiesis remains an urgent hematological problem. In order to solve the problem of regulatory influence, the use of morphological methods is recommended, including the immunohistochemical analysis.

Keywords: hematopoietic stem cell, bone marrow, hematopoietic stem cell niche, microenvironment, lymphoid niche, follicular dendritic cells.

Received: October 8, 2015

Accepted: January 10, 2016

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Role of Patient’s Age and Comorbidities in Therapy of Chronic Lymphocytic Leukemia

LYMPHOID TUMORS , ,

VV Strugov1, EA Stadnik1,2, YuV Virts1, TO Silina1, AYu Zaritskii1,2

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

2 Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Vladimir Vladimirovich Strugov, scientific worker, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; Tel.: +7(906)277-86-64; e-mail: strugov@almazovcentre.ru

For citation: Strugov VV, Stadnik EA, Virts YuV, et al. Role of Patient’s Age and Comorbidities in Therapy of Chronic Lymphocytic Leukemia. Clinical oncohematology. 2016;9(2):162–75 (In Russ).

DOI: 10.21320/2500-2139-2016-9-2-162-175

ABSTRACT

Background & Aims. New schemes of the antitumor therapy of CLL resulted in improvement of survival of relatively young patients. However, the therapy outcomes of elderly patients are still unsatisfactory. Erroneous overestimation of expected toxicity of standard therapeutic regimens in some elderly patients may play a certain role, thus leading to prescription of less effective regimens. Therefore, the urgent problem is to find objective criteria for risk stratification in CLL. The aim of the study is to evaluate the prognostic significance of patient’s age and the CIRS-G index in elderly patients treated with fludarabine-containing regimens in first line treatment outside clinical trials.

Methods. A retrospective analysis of 90 elderly CLL patients, treated with standard FC and FCR regimens in the clinic of internal medicine of the First St. Petersburg State Medical University from 2001 till 2011. The age median was 59 years (range from 43 to 78 years). The comorbidity index was determined for each patient using the CIRS-G score.

Results. The overall response rate did not significantly differ between FC and FCR groups and was equal to 81.6 % and 93.4 %, respectively (p = 0.109). Complete remissions were achieved in 72.3 % of FCR group patients and only in 46.5 % of FC group patients (p = 0.018). The retrospective analysis of treatment tolerability in primary elderly patients with different CIRS-G scores in the routine clinical practice demonstrated that the index has no independent prognostic significance. Among all CIRS-G components (14 organs and systems), only renal and hepatic diseases demonstrated significant correlation with the overall survival rate (p < 0.001 and p = 0.028, respectively).

Conclusion. The creatinine clearance value in the beginning of treatment is the most important predictor of FC and FCR regimen efficacy in elderly patients. The use of the comorbidity index with a 6-score threshold as a contraindication for fludarabine-containing regimens proved to be unjustified.

Keywords: chronic lymphocytic leukemia, CLL, comorbidity index, CIRS-G, FCR.

Received: January 15, 2016

Accepted: February 3, 2016.

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Biopsy of Lungs and Pleura in Hematologic Center

LYMPHOID TUMORS , , , ,

SR Karagyulyan, KI Danishyan, VS Shavlokhov, MA Silaev, GM Galstyan, AV Tochenov, LA Kuz’mina, IV Efimov, SA Shutov, YuV Pliskunova, IA Shupletsova, AM Kovrigina

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

For correspondence: Maksim Anatol’evich Silaev, PhD, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-61-91; e-mail: max-blood@mail.ru

For citation: Karagyulyan SR, Danishyan KI, Shavlokhov VS, et al. Biopsy of Lungs and Pleura in Hematologic Center. Clinical oncohematology. 2016;9(1):42–7 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-42-47

ABSTRACT

Background & Aims. Morphological, immunohistochemical, immunophenotypic, cytogenetic, molecular and genetic and other examinations of tissues affected by oncohematological diseases are obligatory. The aim of this paper is to evaluate findings of lung and pleura biopsies in different medical conditions using two basic techniques: thoracoscopy and diagnostic thoracotomy.

Methods. Results of morphological examination of lung lesions in patients hospitalized in the Hematology Research Center under the Ministry of Health of the Russian Federation are presented. From 2004 till 2014, 76 biopsies of lung and/or parietal pleura were performed in 73 patients aged 19–77 years via thoracoscopic (48) and/or thoracotomic (28) approach.

Results. No thoracoscopy- and thoracotomy-related complications were observed. Bioptate examinations proved to be informative in 66 (86.7%) patients. Lung lesions were most common in lymphoproliferative diseases. Lung involvement in cancer or metastases was twice as common as it has been expected before the biopsy. On the contrary, expected tuberculosis nature of lung lesions in 5 patients was confirmed only in 2 of them. In 18 cases (23.7 %), the cause of lung lesion was other than the expected one, and appropriate adjustments of the therapy were made.

Conclusion. New less invasive methods of biopsy combined with complex laboratory diagnosing comply with current requirements and permit making a correct diagnosis of a pathological process located in lungs.

Keywords: lung biopsy, thoracoscopy, lung lesion, morphological verification, acute respiratory insufficiency.

Received: August 28, 2015

Accepted: December 26, 2015

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Video-Assisted Thoracoscopic Surgery in Diagnosing Lymphomas

LYMPHOID TUMORS , , ,

IG Komarov1,2, SYu Sletina1, MI Komarov2, АА Sukhov1

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

2 Russian Medical Academy of Postgraduate Education, 23 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Igor’ Gennad’evich Komarov, DSci, Professor, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-12-70; e-mail: komarovig@mail.ru

For citation: Komarov IG, Sletina SYu, Komarov MI, Sukhov AA. Video-Assisted Thoracoscopic Surgery in Diagnosing Lymphomas. Clinical oncohematology. 2016;9(1):30–41 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-30-41

ABSTRACT

This article continues a series of papers dwelling on endo-surgery techniques in diagnosing lymphomas. It describes the history of the thoracoscopic surgery and its potential and current use when malignant lymphoproliferative diseases with involvement of chest organs and tissues. It provides brief description of basic instruments, equipment and technique of surgical interventions via the thoracic access. It lists indications and contraindications for the thoracoscopic surgery. In addition, the paper presents analysis of video-assisted thoracoscopic surgeries in 178 patients with suspected malignant lymphoproliferative diseases. During these surgeries, samples for further morphological assessment were obtained from all patients. Lymphomas were confirmed in 120 patients. The article contains two case reports on the video-assisted thoracoscopic interventions performed.

Keywords: lymphoma, diagnostics, video-assisted surgery, thoracoscopy.

Received: November 6, 2015

Accepted: December 24, 2015

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REFERENCES

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    [Komarov IG, Stepanenkova SS, Komarov MI. Video-Assisted Laparoscopic Surgeries in Diagnosing Lymphomas. Klinicheskaya onkogematologiya. 2014;7(4):540–50. (In Russ)]

Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia

LYMPHOID TUMORS , , ,

GA Tsaur1,2,3, C Meyer4, TO Riger1,2, AM Kustanovich5, EV Fleischman6, YuV Ol’shanskaya7, AM Popov7, OI Sokova6, EA Matveeva7, OV Nikulina1,2, AE Drui1,2, OR Arakaev1,2, OV Streneva1,2, SA Rumyantsev7, EV Shorikov1,2, AG Solodovnikov2, LI Savel’ev1,2, R Marschalek4, LG Fechina1

 1 Regional Children’s Clinical Hospital No. 1, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149

2 Research Institute of Medical Cell Technologies, 22a K. Marksa str., Ekaterinburg, Russian Federation, 620026

3 First President of Russia B.N. Yeltsin Ural Federal University , 19 Mira str., Ekaterinburg, Russian Federation, 620002

4 Diagnostic Center of Acute Leukemia, Institute of Pharmaceutical Biology/ZAFES, Goethe-University of Frankfurt, N230, Max-von-Laue Str. 9, Frankfurt am Main Deutschland, 60438

5 Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, 43 Frunzenskaya str., Borovlyany, Minsk District, Belarus, 223053

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

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

For correspondence: Grigorii Anatol’evich Tsaur, PhD, 32 Serafimy Deryabinoi str., Ekaterinburg, Russian Federation, 620149; Tel.: +7(343)216-25-17; e-mail: tsaur@mail.ru

For citation: Tsaur GA, Meyer C, Riger TO, et al. Relation between Genomic DNA Breakpoints in MLL Gene and Treatment Outcome in Infants with Acute Leukemia. Clinical oncohematology. 2016;9(1):22–9 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-22-29

ABSTRACT

Aim. To evaluate the relation between genomic DNA breakpoints in MLL and translocation partner genes (TPG) and clinical parameters of infant AL.

Methods. 68 infants (29 boys and 39 girls with median age of 4.8 mo) with MLL-rearranged acute lymphoblastic leukemia (ALL) (n = 46), acute myeloid leukemia (AML) (n = 20) and mixed phenotype acute leukemia (MPAL) (n = 2) were included in the current study.

Results. 5-year EFS was significantly lower in patients with breakpoints in intron 11 (n = 29) in comparison to patients with breakpoint localized from intron 7 to exon 11 (n = 17) (0.16 ± 0.07 vs 0.38 ± 0.14, p = 0.039). While cumulative incidence of relapse was remarkably higher in the first group of patients (0.74 ± 0.09 vs 0.52 ± 0.17, p = 0.045). Although in Cox regression model including breakpoint location in intron 11 together with age, immunophenotype, initial white blood cell count, initial CNS involvement, type of MLL rearrangements, absolute blast number at day 8 of dexamethasone profase, minimal residual disease (MRD) at time point 4 (TP4) of MLL-Baby protocol, the only significant covariate was the presence of MRD at TP4 (HR 5.994, 95% CI 2.209–16.263, p < 0.001). In 22 AML patients there was not any correlation between breakpoint location and treatment outcome.

Conclusion. Breakpoints in intron 11 of MLL gene led to significantly worse outcome in infants with ALL, treated by MLL-Baby protocol, although this parameter was overcome by MRD-positivity at TP4. The latter was the only independent covariate in multivariate analysis. Our data provide additional information of molecular genetic features of MLL-rearranged infant AL.

Keywords: acute leukemia, infants, 11q23/MLL rearrangements, MLL-Baby, treatment outcome.

Received: September 14, 2015

Accepted: October 20, 2015

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Treatment of Relapsed and Refractory Hodgkin’s Lymphoma in Children

LYMPHOID TUMORS , , , ,

NS Kulichkina, ES Belyaeva, GL Mentkevich, VK Boyarshinov, AS Levashov, IV Glekov, AV Popa

Scientific Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Aleksandr Valentinovich Popa, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-55-03; e-mail: apopa@list.ru

For citation: Kulichkina NS, Belyaeva ES, Mentkevich GL, et al. Treatment of Relapsed and Refractory Hodgkin’s Lymphoma in Children. Clinical oncohematology. 2016;9(1):13–21 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-13-21

ABSTRACT

Background & Aims. Most children with Hodgkin’s lymphoma (HL) can be cured irrespective of the disease stage using modern risk adapted protocols. But 3–5 % of children develop relapse of the disease or refractoriness to the treatment performed. The aim of the study was to perform a comparative analysis of ViGePP vs ICE antitumor treatment regimens in patients with relapsed and refractory Hodgkin’s lymphoma, as well as to evaluate the need in auto-HSCT and the site for a combined chemoradiation therapy in this patient population.

Methods. From June, 2003, till December, 2014, 35 patients with relapsed (18) and refractory (17) HL received chemotherapy based on two regimes: ICE (n = 14; 40 %) and ViGePP (n = 14; 40 %). 7 (20 %) children were switched to another regimen due to a poor antitumor response to the first two courses of chemotherapy.

Results. The direct effectiveness of the therapy was significantly higher in patients on ViGePP as compared to ICE irrespective of the disease status (relapsed or refractory). A complete response was achieved more often in those children with relapse HL whose initial treatment included radiation therapy. Higher survival rates were registered in girls, as well as in children with a complete overall response to the antirelapse therapy. In case of relapses, delayed treatment effects (disease free survival and overall survival) were higher in children treated with 4 courses of ViGePP than 2 courses of ICE. High-dose chemotherapy with subsequent auto-HSCT is not able to overcome refractoriness to the chemotherapy.

Conclusion. Children with relapsed and refractory HL need an intensive antirelapse chemotherapy with subsequent HDC and auto-HSCT to achieve CR.

Keywords: Hodgkin’s lymphoma, children, relapse, refractoriness, auto-HSCT.

Received: November 9, 2015

Accepted: December 25, 2015

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Prognostic Significance of Thymidine Kinase-1 versus β2-Microglobulin and Lactate Dehydrogenase in Lymphoproliferative Diseases

LYMPHOID TUMORS , , , ,

N.K. Parilova1, N.S. Sergeeva1,2, N.V. Marshutina1, N.G. Tyurina1, I.S. Meisner2

1 P.A. Hertzen Moscow Cancer Research Institute, a branch of the National Medical Research Radiological Center under the Ministry of Health of the Russian Federation, 3 Botkinskii pr-d, Moscow, Russia 125284

2 N.I. Pirogov Russian National Research Medical University under the Ministry of Health of the Russian Federation, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Natal’ya Konstantinovna Parilova, junior researcher, 3 2nd Botkinskii pr-d, Moscow, Russia, 125284; Tel.: + 7(495)945-74-15; e-mail: parilochka@mail.ru.

For citation: Parilova NK, Sergeeva NS, Marshutina NV, et al. Prognostic Significance of Thymidine Kinase-1 versus b2-Microglobulin and Lactate Dehydrogenase in Lymphoproliferative Diseases. Clinical oncohematology. 2016;9(1):6–12 (In Russ).

DOI: 10.21320/2500-2139-2016-9-1-6-12

ABSTRACT

Background & Aims. Lactate dehydrogenase (LDH) and b2-microglobulin (b2-MG) are usually detected as serological tumor markers (TM) in malignant lymphoproliferative diseases (LPD); however, their use in monitoring of chemotherapy (CT) is limited due to their low sensitivity and specificity. The aim of this paper is to evaluate the prognostic value of baseline levels of thymidine kinase-1 (TK-1) versus b2-MG and LDH in patients with non-Hodgkin’s lymphomas (NHL) and Hodgkin’s lymphoma (HL) and to assess their clinical significance of changes in these parameters during CT as criteria of its effectiveness.

Methods. TK-1, b2-MG and LDH levels were evaluated in 61 NHL patients and 34 HL patients at baseline and after each subsequent CT cycle. The average age of patients enrolled in the study was 42.5 years (range 18–77 years). Of them 45 were men and 50 were women. Marker levels were determined in serum using the following tests: enzyme-linked immunosorbent assay (ELISA) for TK-1, immunoturbidimetry for b2-MG, and biochemical method for LDH. Discriminatory levels specified by test-system manufacturers were used in calculations: 50 DU/l for TK-1, 800–2400 mg/l for b2-MG, and 225–450 U/l for LDH.

Results. The study demonstrated that lower baseline levels of all three TM were associated with higher probability of complete or partial remission, and the statistical difference was higher. Baseline levels of TK-1 < 150 DU/l and b2-MG < 2200 mg/l may serve as prognostic factors of higher probability of achievement of complete or partial remission.

Conclusion. 4-fold increase in TK-1 serum activity from baseline after the 1st course of CT can predict the effectiveness of antitumor therapy. At the same time, no significant associations between b2-MG and LDH serum levels changes during the treatment and efficacy of the treatment were found.

Keywords: thymidine kinase-1, b2-microglobulin, lactate dehydrogenase, Hodgkin’s lymphoma, non-Hodgkin’s lymphomas.

Received: June 17, 2015

Accepted: November 3, 2015

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REFERENCES

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  9. Pan ZL, Ji XY, Shi YM, et al. Serum thymidine kinase 1 concentration as a prognostic factor of chemotherapy-treated non-Hodgkin’s lymphoma patients. J Cancer Res Clin Oncol. 2010;136(8):1193–9. doi: 10.1007/s00432-010-0769-z.
  10. Парилова Н.К., Сергеева Н.С., Тюрина Н.Г. и др. Сывороточные уровни тимидинкиназы-1 (ТК-1) у больных с лимфопролиферативными заболеваниями. Онкология. Журнал им. П.А. Герцена. 2012;1:33–8.
    [Parilova NK, Sergeeva NS, Tyurina NG, et al. Serum thymidine kinase 1 (TK-1) levels in patients with lymphoproliferative disorders. Onkologiya. Zhurnal im PA Gertsena. 2012;1:33–8. (In Russ)]
  11. Bogni A, Cortinois A, Grasseli G, et al. Thymidine kinase (TK) activity as a prognostic parameter of survival in lymphoma patients. J Biol Regul Homeost Agents. 1994;8(4):10.
  12. Nisman B, Nechushtan H, Biran H, et al. Serum thymidine kinase 1 activity in the prognosis and monitoring of chemotherapy in lung cancer patients: a brief report. J Thorac Oncol. 2014;9(10):1568–72. doi: 10.1097/jto.0000000000000276.
  13. Nisman B, Nchushtan H, Biran H, et al. Serum thymidine kinase 1 activity in prognosis and monitoring chemotherapy in lung cancer patients. Tumor Biol. 2014;35(1):22–3. doi: 10.1097/jto.0000000000000276.

 

New Aspects of Pathophysiology and Pathomorphology of Renal Lesions in Malignant Tumors

LYMPHOID TUMORS , , , , , ,

B.T. Dzhumabaeva, L.S. Biryukova

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

For correspondence: Boldukyz Tolgonbaevna Dzhumabaeva, DSci, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)613-24-68; e-mail: bola.blood@yandex.ru

For citation: Dzhumabaeva BT, Biryukova LS. New Aspects of Pathophysiology and Pathomorphology of Renal Lesions in Malignant Tumors. Clinical oncohematology. 2015;8(4):390–396 (In Russ).

DOI: 10.21320/2500-2139-2015-8-4-390-396

ABSTRACT

Glomerular injuries associated with malignancy are rare and they are morphologically heterogeneous. Although the pathophysiologic interrelations between a tumor and glomerulopathy are not clear, molecular mechanisms of paraneoplastic glomerulopathies and pathologic features of renal lesions in solid tumors, lymphoproliferative and myeloproliferative disorders have been discovered over recent decades.

Keywords: membranous nephropathy, immunotactoid glomerulopathy, minimal-change glomerulopathy, fibrillary glomerulonephritis, renal failure, anti-PLA2R1 antibody, c-mip protein.

Received: March 19, 2015

Accepted: October 23, 2015

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Pomalidomide for Treatment of Relapsed and Refractory Multiple Myeloma

LYMPHOID TUMORS , ,

S.V. Semochkin

N.I. Pirogov Russian National Research Medical University under the Ministry of Health of the Russian Federation, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Sergei Vyacheslavovich Semochkin, DSci, Professor, 1 Ostrovityanova str., Moscow, Russian Federation, 117997; Tel.: +7(495)653-14-78; e-mail: s.semochkin@gmail.com

For citation: Semochkin SV. Pomalidomide for Treatment of Relapsed and Refractory Multiple Myeloma. Clinical oncohematology. 2015;8(4):379–389 (In Russ).

DOI: 10.21320/2500-2139-2015-8-4-379-389

ABSTRACT

Pomalidomide is a third-generation immunomodulatory drug recommended for patients with multiple myeloma refractory to lenalidomide and bortezomib. The safety profile is optimized for application in patients with intensive and continuous anti-tumor treatment. Pomalidomide was approved by the Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) in 2013 for use in patients with relapsed and refractory MM who have received at least two prior therapies, including lenalidomide and bortezomib, and have demonstrated disease progression on their last therapy or within 60 days after completion of the last therapy. Registration of pomalidomide for similar indications in Russia is pending in 2015. Pomalidomide has a similar mechanism of action with the other immunomodulators. The drug produces a direct cytostatic effect and causes an indirect effect by affecting the bone marrow microenvironment and T/NK-cells immunity. The recommended starting dose of pomalidomide is 4 mg daily (1–21/28) combined with low-dose dexamethasone 40 mg weekly for young patients or 20 mg for patients older than 75 years. The treatment should be performed till disease progression or unacceptable toxicity. This review summarizes current recommendations for dose adjustment depending on tolerance and prevention of thrombotic complications. The article presents author’s own clinical experience of successful application of pomalidomide for the management of a patient at high cytogenetic risk with «double» refractoriness to lenalidomide and bortezomib and preceding intensive anti-tumor treatment. The life expectancy was about 16 months after initiation of pomalidomide; this fact is consistent with literature data.

Keywords: pomalidomide, immunomodulatory drugs, multiple myeloma.

Received: April 8, 2015

Accepted: October 20, 2015

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