LYMPHOID TUMORS

Overcoming Resistance in Relapsed Anaplastic Large-Cell Lymphoma, ALK-Positive (Literature Review and Clinical Experience)

LYMPHOID TUMORS , , , ,

YuE Vinogradova1, NG Chernova2

1 IM Sechenov First Moscow State Medical University, 8 bld. 2 Trubetskaya Str., Moscow, Russian Federation, 119991

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

For correspondence: Yuliya Eikhenovna Vinogradova, MD, PhD, 8 bld. 2 Trubetskaya str., Moscow, Russian Federation, 119991; Tel.: +7(495)609-14-00, +7(916)195-68-57; е-mail: jvinogr@gmail.com

For citation: Vinogradova YuE, Chernova NG. Overcoming Resistance in Relapsed Anaplastic Large-Cell Lymphoma, ALK-Positive (Literature Review and Clinical Experience). Clinical oncohematology. 2019;12(2):179–84.

DOI: 10.21320/2500-2139-2019-12-2-179-184

ABSTRACT

Peripheral T-cell lymphomas (PTCL) are characterized by unfavorable prognosis and poorer survival in comparison with B-cell lymphomas. Probability of remission on first-line PTCL therapy is not higher than 60 % with high relapse rate. Long-term remission in PTCL relapses/progression cases typically fails to be achieved. The present article provides literature review and the authors’ own clinical experience in the management of anaplastic large-cell lymphoma, ALK-positive with primary skin and soft tissue lesions in an 65-year old female patient. After NHL-BFM-90 intensive chemotherapy the first 5,5-year complete remission was achieved in this patient. Afterwards a СНОР therapy-resistant relapse was identified. Chemotherapy-resistance of tumor was successfully overcome by adding of epigenetic drugs to cytostatic antitumor therapy. The duration of second complete remission is 3 years. Oncohematological diseases with either initial chemotherapy-resistance or the resistance acquired during antitumor therapy are most efficiently treated by various drug combinations including monoclonal antibodies, epigenetic drugs, and cytostatic therapy.

Keywords: anaplastic large-cell lymphoma, ALK-positive, skin involvements, resistance associated with relapse, epigenetic drugs.

Received: July 26, 2018

Accepted: January 15, 2019

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Prognostic Value of PRAME Activity in Tumor Cells of Follicular Lymphoma

LYMPHOID TUMORS ,

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 (p = 0.043) and larger tumor mass (p = 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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Intermediate Results of Prospective Observational Study: The 2-year Experience of Ibrutinib Therapy in Relapsed/Refractory Mantle Cell Lymphoma in Clinical Practice

LYMPHOID TUMORS , , ,

VI Vorob’ev, VA Zherebtsova, EI Dubrovin, LA Bychenkova, YuB Kochkareva, LA Mukha, VL Ivanova, NK Khuazheva, VV Ptushkin

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

For correspondence: Vladimir Ivanovich Vorob’ev, MD, PhD, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284; e-mail: morela@mail.ru

For citation: Vorob’ev VI, Zherebtsova VA, Dubrovin EI, et al. Intermediate Results of Prospective Observational Study: The 2-year Experience of Ibrutinib Therapy in Relapsed/Refractory Mantle Cell Lymphoma in Clinical Practice. Clinical oncohematology. 2019;12(2):165-72.

DOI: 10.21320/2500-2139-2019-12-2-165-172

ABSTRACT

Aim. To assess efficacy and toxicity of ibrutinib monotherapy in patients with relapsed/refractory mantle cell lymphoma (MCL).

Materials & Methods. In this group of patients ibrutinib has been used since April 2016. Ibrutinib administration criteria were the age > 18 years and the confirmed MCL diagnosis with nuclear hyperexpression of cyclin D1 and t(11;14)(q13;q32) translocation. Poor physical status, pancytopenia, infectious complications (except for life-threatening conditions), blastoid variant, and the number of previous treatment lines were not regarded as contraindications to ibrutinib therapy. Oral ibrutinib was administered once a day at a dose of 560 mg before progression and until intolerable toxicity was observed.

Results. From April 20, 2016 to April 6, 2018 ibrutinib therapy was provided to 42 patients with relapsed/refractory MCL. The median age was 69 years (range 40–81); 64 % of patients were men; ECOG > 2 was registered in 14 % of patients; 38 % of patients had blastoid variant; the median number of previous treatment lines was 2 (range 1–11). The overall response rate was 85 % (35 % were in complete remission); 57 % (24/42) of patients remain on ibrutinib treatment for the period of 4–667 days. The median event-free survival (EFS) was 365 days (95% confidence interval was 31–698 days). The median overall survival was not achieved. In blastoid variant the median EFS was 92 days, in the alternative group the median was not achieved and EFS was 76 % for 12 months (p < 0.001). In the majority of cases ibrutinib was well tolerated by patients. The most common complications were myalgia and muscle cramps (57 % cases), diarrhea (46 %, and grade 3 in 5 % cases), hemorrhagic complications (63 %, all of them of grade 1–2), and arrhythmia (7 %). Infectious complications were reported in 31 % of patients. In one case the start of ibrutinib treatment appeared to be problematic due to neutropenia of grade 4. Relative dose intensity was > 98 % (range 91.6–100 %). In 10 (24 %) patients ibrutinib treatment had to be adjusted (dose reduction or treatment interruption) due to toxicity and planned surgeries. None of ibrutinib recipients had to completely discontinue ibrutinib therapy due to complications.

Conclusion. These data on the use of ibrutinib in actual clinical practice are comparable with the results of international multicenter studies (PCYC-1104, SPARK, and RAY). Reduced toxicity profile and rather high speed of antitumor response allow for ibrutinib administration in cases of poor physical status, low blood count, and even infectious complications. However, some adverse effects are manifested not earlier than after 6-month treatment, which calls for continuous monitoring, especially when preparing for surgeries.

Keywords: mantle cell lymphoma, ibrutinib, relapse, refractory course, targeted therapy.

Received: November 4, 2018

Accepted: February 11, 2019

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Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues

LYMPHOID TUMORS , , , , , ,

KD Kaplanov1,2, NP Volkov1, TYu Klitochenko1, IV Matveeva1, AL Shipaeva1, MN Shirokova1, NV Davydova3, EG Gemdzhian4, DS Abramov5, DM Konovalov5, GL Snigur2, NA Red’kina1

1 Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

2 Volgograd Medical Scientific Center, 1G Rokossovskogo str., Volgograd, Russian Federation, 400081

3 Consultation and Diagnosis Polyclinic No. 2, 114A Angarskaya str., Volgograd, Russian Federation, 400081

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

5 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117997

For correspondence: Kamil’ Daniyalovich Kaplanov, MD, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Volkov NP, Klitochenko TYu, et al. Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues. Clinical oncohematology. 2019;12(2):154–64.

DOI: 10.21320/2500-2139-2019-12-2-154-164

ABSTRACT

Background & Aims. At least one third of patients with diffuse large B-cell lymphoma (DLBCL) are resistant to first-line therapy. R-CHOP chemo-immunotherapy does not yield acceptable results in high-risk patients. Effectiveness of options based either on increasing the dose intensity or on including auto-HSCT into the first-line therapy was not supported by the results of controlled studies. With this background the present study focuses on options, issues and failures of first-line on the basis of long-term follow-up of DLBCL patient population in the Volgograd Region.

Materials & Methods. From 2004 to 2017 the population-based registry of the Hematology Department in the Volgograd Regional Clinical Oncology Dispensary included all 492 primary DLBCL patients: 235 (48 %) men and 257 (52 %) women aged 18 to 88 years. Mean and median age was 59 and 61 years, respectively. CHOP therapy was administered to 206 (42 %) patients, and 223 (45 %) patients received R-CHOP. Other regimens including NHL-BFM-90 and R-DA-EPOCH were used only in 63 (13 %) patients. Second- and third-line therapies were administered to 145 (30 %) and 54 (11 %) patients, respectively. Value of the International Prognostic Index (IPI) and immunomorphologic characteristics was determined by multivariate Cox regression analysis. Pharmacoeconomic aspect of first-line therapy failures was analyzed using Markov model.

Results. Improvement of DLBCL therapy effects with the use of R-CHOP chemo-immunotherapy is particularly obvious in the groups with favorable and intermediate prognosis with 5-year overall survival (OS) of 90 % and 69 %, respectively. R-CHOP results are not considered to be satisfactory in the high-risk group: 5-year OS was 38 %. Pharmacoeconomic analysis proves the advantage of chemo-immunotherapy strategy in comparison with the period before rituximab era in terms of the life years gained (LYG) and the incremental cost-effectiveness ratio (ICER). With respect to immunotherapy effects the most significant immunomorphologic parameter is bcl-2 tumor cell expression. In the group of patients with bcl-2 > 50 % 5-year OS was 61 % with median of 88 months, event-free survival (EFS) was 52 % with median of 62 months. In the group without bcl-2 expression above the threshold 5-year OS and EFS were 88 % and 75 %, respectively, medians were not achieved. With c-myc and bcl-2 coexpression EFS and OS appeared to be even worse: 5-year EFS was 29 % with median of 6 months, and 5-year OS was 31 % with median of 15 months.

Conclusion. The analysis of actual practice demonstrates the need for new options of first-line therapy for DLBCL high-risk patients and also for introducing new discriminating prognostic factors which include the IPI-independent ones.

Keywords: diffuse large B-cell lymphoma, R-CHOP, chemoimmunotherapy, survival, pharmacoeconomics, Markov model, life years gained (LYG), incremental cost-effectiveness ratio (ICER).

Received: July 16, 2018

Accepted: January 10, 2019

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Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Russian Multicenter Clinical Trial

LYMPHOID TUMORS ,

SN Bondarenko1, EN Parovichnikova2, AA Maschan3, OYu Baranova4, TV Shelekhova5, VA Doronin6, VYa Mel’nichenko7, KD Kaplanov8, OS Uspenskaya9, AN Sokolov2, NV Myakova3, IS Moiseev1, IV Markova1, EI Darskaya1, AG Smirnova1, TA Bykova1, BI Ayubova1, IA Samorodova1, EV Babenko1, IM Barkhatov1, TL Gindina1, AD Kulagin1, BV Afanas’ev1

1 RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

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

3 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117997

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

5 VI Razumovskii Saratov State Medical University, 112 Bol’shaya Kazach’ya str., Saratov, Russian Federation, 410012

6 Municipal Clinical Hospital No. 40, 7 Kasatkina str., Moscow, Russian Federation, 129301

7 NI Pirogov Russian National Medical Center of Surgery, 70 Nizhnyaya Pervomaiskaya str., Moscow, Russian Federation, 105203

8 Volgograd Regional Clinical Oncologic Dispensary, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

9 Leningrad Regional Clinical Hospital, 45–49 Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

For correspondence: Sergei Nikolaevich Bondarenko, MD, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-62-72; e-mail: dr.sergeybondarenko@gmail.com

For citation: Bondarenko SN, Parovichnikova EN, Maschan AA, et al. Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Russian Multicenter Clinical Trial. Clinical oncohematology. 2019;12(2):145–53.

DOI: 10.21320/2500-2139-2019-12-2-145-153

ABSTRACT

Background. Recent advances in the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R ALL) are attributed to the implementation of immunotherapy methods which include blinatumomab, the bispecific engager of a patient’s endogenous T-cells (Blincyto™, Amgen®) (BC).

Aim. To assess BC efficacy and toxicity in the treatment of R/R ALL patients with persistence of minimal tumor clone before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Materials & Methods. The trial included 66 B-ALL patients with CD19+ aged 18 to 72 years, 23 (35 %) of them with measurable minimal residual disease (MRD+) and 43 (65 %) with R/R ALL. In 18 (27 %) patients BC was administered after prior allo-HSCT.

Results. In the overall group 2-year overall survival (OS) and disease-free survival (DFS) in patients with response to BC treatment were 53 % and 38 % respectively. In the R/R ALL group complete remission (CR) was achieved in 29 (67 %) patients including 24 (83 %) patients with negative MRD. CR rate was higher in standard cytogenetic risk group (73 %) in comparison with high-risk group (59 %). In patients with more or less than 50 % blast cells in bone marrow CR rate was 85 % and 61 %, respectively. When BC was administered after prior allo-HSCT and without it CR rate was 80 % and 60 %, respectively. In R/R ALL patients with response to BC 2-year OS and DFS were 40 % and 26 %, respectively, in the MRD+ group of ALL patients they were 66 % and 51 %, respectively. Relapse rate was lower in the group with allo-HSCT than in the group without it, i.e. 21 % vs. 55 %. Adverse events of grade 3–4 were observed in 25 (38 %) patients. In 11 (16 %) patients BC therapy had to be discontinued, in 5 (7 %) patients it was terminated prior to the scheduled date.

Conclusion. BC efficacy is higher in the MRD+ group and in R/R ALL patients with smaller tumor mass. BC treatment after allo-HSCT yields remissions in most patients and can be combined with immune-adoptive therapy.

Keywords: acute lymphoblastic leukemia, targeted therapy, blinatumomab.

Received: August 22, 2018

Accepted: January 18, 2019

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  9. Klinger M, Brandl C, Zugmaier G, et al. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell–engaging CD19/CD3-bispecific BiTE antibody blinatumomab. Blood. 2012;119(26):6226–33. doi: 10.1182/blood-2012-01-400515.

  10. Topp MS, Gokbuget N, Stein AS, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16(1):57–66. doi: 10.1016/s1470-2045(14)71170-2.

  11. Gokbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018;131(14):1522–31. doi: 10.1182/blood-2017-08-798322.

  12. Kantarjian H, Stein AS, Gokbuget N, et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017;376(9):836–47. doi: 10.1056/NEJMoa1609783.

  13. Zugmaier G, Gokbuget N, Klinger M, et al. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood. 2015;126(24):2578–84. doi: 10.1182/blood-2015-06-649111.

Epidemiology of Multiple Myeloma in Novosibirsk (Siberian Federal District)

LYMPHOID TUMORS , , , , ,

NV Skvortsova1, TI Pospelova1, IB Kovynev1, GS Soldatova2, IN Nechunaeva3

1 Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091

2 Novosibirsk National Research State University, 2 Pirogova str., Novosibirsk, Russian Federation, 630090

3 Municipal Clinical Hospital No. 2 of Novosibirsk Region, Center of Hematology, 21 Polzunov str., Novosibirsk, Russian Federation, 630051

For correspondence: Nataliya Valer’evna Skvortsova, MD, PhD, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091; Tel.: +7(905)955-59-91; e-mail: nata_sk78@mail.ru.

For citation: Skvortsova NV, Pospelova TI, Kovynev IB, et al. Epidemiology of Multiple Myeloma in Novosibirsk (Siberian Federal District). Clinical oncohematology. 2019;12(1):86–94.

DOI: 10.21320/2500-2139-2019-12-1-86-94

ABSTRACT

Aim. To analyze major epidemiological parameters of multiple myeloma, i.e. registered incidence, prevalence, mortality, and survival in Novosibirsk, megalopolis in Siberian Federal District.

Materials & Methods. The study covered medical records of 335 patients with newly diagnosed multiple myeloma (MM) treated from January 1, 2006 to December 31, 2016 at the Center of Hematology in Novosibirsk. Median age was 67 years (range 30–89), the trial enrolled 218 (65 %) women and 117 (35 %) men.

Results. Over the last decade the mean registered MM incidence in Novosibirsk increased by 1.6 times, and MM prevalence increased by 4.9 times. These parameters correspond to 2.4 and 13.8 per 100,000 population per year, respectively, with the linear trend of growth which demonstrates not only the increased number of patients with newly diagnosed MM, but the increased longevity of them. MM incidence and prevalence parameters are significantly higher in women than in men, which most probably can be accounted for by specific administrative factors in the Novosibirsk region. Yearly mortality of MM patients decreased from 28.3 % to 8.2 % with a negative linear trend over the entire analyzed period, which is most likely to be associated with availability of new drugs and transplantation procedures.

Conclusion. The obtained epidemiological data will enable to plan the provision of timely and effective care for MM patients and to elaborate a system of judicious allocation of costly equipment and drugs.

Keywords: multiple myeloma, epidemiology, registered incidence, prevalence, mortality, survival.

Received: September 24, 2018

Accepted: December 27, 2018

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Diagnosis of Acute Lymphoblastic Leukemia Originating From T-Lineage Precursors and Approaches to Minimal Residual Disease Monitoring

LYMPHOID TUMORS , , ,

OA Chernysheva, LYu Grivtsova, IN Serebryakova, NA Kupryshina, EN Sholokhova, MA Shervashidze, AD Palladina, BV Kurdyukov, AV Popa, NN Tupitsyn

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

For correspondence: Ol’ga Alekseevna Chernysheva, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-14-30; e-mail: beznos.olga@gmail.com

For citation: Chernysheva OA, Grivtsova LYu, Serebryakova IN, et al. Diagnosis of Acute Lymphoblastic Leukemia Originating From T-Lineage Precursors and Approaches to Minimal Residual Disease Monitoring. Clinical oncohematology. 2019;12(1):79–85.

DOI: 10.21320/2500-2139-2019-12-1-79-85

ABSTRACT

Background. Minimal residual disease (MRD) is an independent prognostic factor in acute lymphoblastic leukemia (ALL) in children. The immunological assessment of MRD cell count is based on aberrant immunophenotype of tumor lymphoblasts. However, in the case of ALL originating from T-lineage precursor cells (T-ALL) no clear aberrancy criteria have been defined, yet. Flow-cytometric MRD assessment in T-ALL can be based on characteristics of normal T-cell ontogenesis, i.e. the absence of normal T-lineage precursor cells (T-LP) in bone marrow.

Aim. To assess the feasibility of immunological method of flow cytometry for MRD detection based on T-LP immunophenotype on Days 15 and 33 of treatment of T-ALL children.

Materials & Methods. The analysis included the data on primary immunophenotype and MRD assessment on Dayы 15 and 33 of treatment of 31 T-ALL patients in the age of 2–17 years. In the majority of cases (61.3 %) the cortical/thymic immuno-subvariant of ALL was detected, in the rest of cases (38.7 %) it was the pre-T-cell one. Diagnosis was based on cumulative results of morphocytochemical and immunological bone marrow analyses. Assessing the MRD state the morphological and immunological analyses of bone marrow aspirate were carried out in parallel with one and the same tube. All patients enrolled in the trial were treated at Scientific Research Institute of Pediatric Oncology and Hematology of NN Blokhin National Medical Cancer Research Center according to the ALL IC-BFM 2009 protocol.

Results. Our study demonstrated that at all therapy stages MRD can be assessed by the unified immunological method based on detecting cyCD3+CD7+/++smCD3– (T-LP) immunophenotype cells. It is important to ensure that the correct clones of monoclonal antibodies are used for detecting CD3 cytoplasmic and membrane molecules (UCHT1 and SK7, respectively). Standard risk group included no patients. The majority of patients (76.2 %) treated according to ALL IC-BFM 2009 protocol were assigned to medium risk group on Day 15 of treatment. By Day 33 a quarter of them (25 %) was included into high risk group.

Conclusion. The capabilities of multicolor flow cytometry allow for the most complete characterization of primary immunophenotype of tumor T-cell lymphoblasts for further search of leukemia-associated immunophenotypes. Specific ontogenesis features of normal T-cells enable unification of immunological approaches to MRD assessment at all stages of T-ALL therapy.

Keywords: T-lineage acute lymphoblastic leukemia, multicolor flow cytometry, minimal residual disease, leukemia-associated immunophenotype.

Received: June 21, 2018

Accepted: December 18, 2018

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Prognostic Value of the PRAME Gene Expression in T-Cell Lymphoproliferative Disorders

LYMPHOID TUMORS , ,

EA Penskaya1, VA Misyurin2, AE Misyurina1, SK Kravchenko1, LG Gorenkova1, LV Plastinina1, VV Tikhonova2, YuP Finashutina2, NA Lyzhko2, NN Kasatkina2, LA Kesaeva2, ON Solopova2, AV Misyurin2

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

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

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: Penskaya EA, Misyurin VA, Misyurina AE, et al. Prognostic Value of the PRAME Gene Expression in T-Cell Lymphoproliferative Disorders. Clinical oncohematology. 2019;12(1):73–78.

DOI: 10.21320/2500-2139-2019-12-1-73-78

ABSTRACT

Background. T-cell lymphomas (T-CL) represent a heterogeneous group of malignant lymphoproliferative disorders characterized by unfavorable prognosis. The cancer-testis PRAME gene is notable for its spontaneous expression in transformed cells as observed in solid tumors, B-cell lymphoproliferative and chronic myeloproliferative diseases. Activity and clinical significance of PRAME in T-CL was not studied before, which determines the relevance and provides ground for the present trial.

Aim. To assess the clinical significance of the PRAME gene expression in T-CL.

Materials & Methods. PRAME gene expression level was measured in samples of lymph nodes, blood, and bone marrow from 35 T-CL patients. Among them 3 patients received allogeneic hematopoietic stem cell transplantation, and 6 patients received autologous hematopoietic stem cell transplantation. A correlation was established between the PRAME expression in bone marrow and peripheral blood with morphological markers of disseminated disease with bone marrow lesions and leukemic blood. PRAME expression level was correlated with survival parameters and tumor proliferative activity (Ki-67).

Results. PRAME activity was observed in 21 (60 %) patients. PRAME hyperexpression is associated with advanced stages of disease (p = 0.0734), bone marrow lesions (p = 0.0289), leukemic blood (p = 0.0187), worsening of the overall survival (OS) (p = 0.0787) and event-free survival (EFS) (p = 0.7185), also after hematopoietic stem cell transplantation (p = 0.2661 for OS and p = 0.0452 for EFS), and with a high Ki-67 expression level (p = 0.0155).

Conclusion. PRAME expression in T-CL is often observed and related with unfavorable clinical prognosis.

Keywords: PRAME, T-cell lymphoproliferative disorders, prognostic value.

Received: April 24, 2018

Accepted: December 27, 2018

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Clinical and Hematological Predictors of Response to First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma

LYMPHOID TUMORS , , ,

SV Samarina1, EL Nazarova1, NV Minaeva1, EN Zotina1, IV Paramonov1, SV Gritsaev2

1 Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

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

For correspondence: Svetlana Valer’evna Samarina, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; e-mail: samarinasv2010@mail.ru

For citation: Samarina SV, Nazarova EL, Minaeva NV, et al. Clinical and Hematological Predictors of Response to First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019;12(1):68–72.

DOI: 10.21320/2500-2139-2019-12-1-68-72

ABSTRACT

Aim. To assess the prognostic value of clinical and hematological parameters used by hematologists for risk stratification in diffuse large B-cell lymphoma (DLBCL), and to justify the need for discovering new prognostic factors.

Methods. The trial included 101 patients (48 men and 53 women) with newly diagnosed DLBCL at the age of 18–80 years (median age 58 years). The patients received R-CHOP as first-line therapy. Depending on their response all patients were stratified into 4 groups: with complete response (CR; n = 58), partial response (PR; n = 15), resistance to first-line therapy (n = 19), and early relapses (ER; n = 9). Median follow-up was 22 months (range 2–120 months).

Results. In terms of age influence on the efficacy of R-СНОР as first-line therapy no significant differences were established in regard to response in patients younger and older than 65 years. Statistically significant differences were observed while analyzing two parameters of International Prognostic Index (IPI; disease stage and extranodal lesions) and B-symptoms in the CR and therapy-resistant groups. With respect to the same parameters no significant differences were found in the CR and ER groups. Median 2-year disease-free survival was not achieved in patients with CR. In patients with PR it was 12 months. Median 2-year overall survival in patients with CR, PR, and ER was not achieved, and in patients with therapy-resistant DLBCL it was 10 months.

Conclusion. Results of the trial confirm prognostic value of factors applied for risk stratification in DLBCL. However, variability of clinical course of the disease, especially with a low IPI score, suggests the need for new prognostic parameters associated with the course of DLBCL.

Keywords: diffuse large B-cell lymphoma, prognosis, induction therapy, survival.

Received: June 5, 2018

Accepted: December 3, 2018

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REFERENCES

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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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