diffuse large B-cell lymphoma

Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA ,

EV Vaneeva, VA Rosin, DA Dyakonov, SV Samarina, IV Paramonov

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

For correspondence: Elena Viktorovna Vaneeva, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027; Tel.: +7(922)975-23-34; e-mail: vaneeva.elena.vic@mail.ru

For citation: Vaneeva EV, Rosin VA, Dyakonov DA, et al. Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2022;15(2):140–7. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-140-147

ABSTRACT

Aim. To assess the prognostic value of pAKT1 and рSyk expression in DLBCL.

Materials & Methods. The study enrolled 100 patients with newly diagnosed DLBCL treated with R-CHOP first-line immunochemotherapy. The relative count of pAKT1- and pSyk-expressing tumor cells was determined by immunohistochemical and morphometric methods. The expression cut-off of these proteins was calculated by ROC analysis. The relationship of protein expression with clinical parameters of DLBCL was analyzed by Fisher’s exact two-tailed test. The 5-year overall (OS) and progression-free (PFS) survivals were estimated by Kaplan-Meier method (log-rank test).

Results. High pAKT1 expression was associated with advanced DLBCL stages, International Prognostic Index > 2, serum lactate dehydrogenase concentration above normal, failures of R-CHOP therapy, as well as worse OS and PFS. No correlation between рSyk expression and clinical lymphoma characteristics was found. The worst 5-year OS (27.6 %) was reported in cases of pAKT1 and pSyk co-overexpression (hazard ratio [HR] 5.2; 95% confidence interval [95% CI] 2.49–10.9; p < 0.001). A similar trend was observed for PFS (HR = 3.3; 95% CI 1.54–7.30; p = 0.002).

Conclusion. Overexpression of pAKT1 is an informative indicator of a poor DLBCL prognosis. Co-overexpression of pAKT1 and рSyk markers is associated with worse OS and PFS compared to their isolated expressions and other co-expression variants.

Keywords: diffuse large B-cell lymphoma, pAKT1 and pSyk expression, overall survival, progression-free survival.

Received: November 17, 2021

Accepted: March 2, 2022

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Treatment of Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis

AUTOIMMUNE THROMBOCYTOPENIA

AS Luchinin

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

For correspondence: Aleksander Sergeevich Luchinin, MD, PhD, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027; Tel.: +7(919)506-87-86; e-mail: glivec@mail.ru

For citation: Luchinin AS. Treatment of Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Systematic Review and Meta-Analysis. Clinical oncohematology. 2022;15(2):130–9. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-130-139

ABSTRACT

Background. Up to now, R-CHOP-21 therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) has been a standard option in the treatment of newly diagnosed diffuse large B-cell lymphoma (DLBCL). About 40–50 % of patients, however, show refractoriness to this therapy or develop early relapses.

Results. The outcomes of 22 clinical trials enrolling 9879 DLBCL patients were analyzed. The efficacies of different R-CHOP-21 therapy regimens were compared, and the progression-free-survivals were estimated. The network meta-analysis showed that, in the total cohort, the most effective first-line regimens were VenR-CHOP (hazard ratio [HR] 0.61; 95% confidence interval [95% CI] 0.37–1.00) and Pola-R-CHP (HR = 0.73; 95% CI 0.47–1.12). For non-GCB (ABC) subtype patients less than 60 years of age, R-ACVBP (HR = 0.31; 95% CI 0.12–0.79) and IR-CHOP (HR = 0.56; 95% CI 0.36–0.86) regimens appeared to be more effective than R-CHOP-21.

Conclusion. Today, the newly diagnosed DLBCL can be treated not only with R-CHOP-21, but also with alternative and more effective regimens. Their assignment, however, needs to be strictly personalized. IR-CHOP and R-ACVBP therapies can be administered in patients with non-GCB (ABC) subtype of DLBCL, if they are under 60 years of age. The list of these regimens can be further extended to include novel drugs, such as polatuzumab vedotin (its efficacy was confirmed by a randomized clinical trial) and venetoclax (its efficacy was confirmed by a non-randomized clinical trial).

Keywords: diffuse large B-cell lymphoma, meta-analysis.

Received: November 24, 2021

Accepted: March 7, 2022

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Pharmacoeconomic Analysis of R-DA-EPOCH and R-mNHL-BFM-90 Combination Immunochemotherapy in Patients with Prognostically Unfavorable Diffuse Large B-Cell Lymphoma within Randomized Multi-Center Clinical Trial DLBCL-2015

AUTOIMMUNE THROMBOCYTOPENIA

MO Bagova1, AU Magomedova1, SK Kravchenko1, RI Yagudina2, VG Serpik2, SM Kulikov1, YuA Chabaeva1

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

2 NA Semashko National Scientific Research Institute for Public Health, 12 bld. 1 Vorontsovo pole str., Moscow, Russian Federation, 105064

For correspondence: Madina Olegovna Bagova, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(938)913-43-83; e-mail: mbagova89@mail.ru

For citation: Bagova MO, Magomedova AU, Kravchenko SK, et al. Pharmacoeconomic Analysis of R-DA-EPOCH and R-mNHL-BFM-90 Combination Immunochemotherapy in Patients with Prognostically Unfavorable Diffuse Large B-Cell Lymphoma within Randomized Multi-Center Clinical Trial DLBCL-2015. Clinical oncohematology. 2021;14(3):321–32. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-321-332

ABSTRACT

Aim. Pharmacoeconomic analysis of R-DA-EPOCH and R-mNHL-BFM-90 combination immunochemotherapy in patients with prognostically unfavorable diffuse large B-cell lymphoma within randomized multi-center clinical trial DLBCL-2015.

Materials & Methods. The pharmacoeconomic analysis conducted between September 2018 and February 2020 was based on the treatment data of 22 patients enrolled in the DLBCL-2015 randomized multi-center clinical trial. This paper deals with the estimation of treatment outcomes in only one center, i.e., the National Research Center for Hematology. The R-DA-EPOCH induction therapy was administered to 14 out of 22 patients, 8 patients received the R-mNHL-BFM-90 block treatment. Within the R-DA-EPOCH group the second-line therapy was administered subsequently to 5 (36 %) out of 14 patients with partial remission or disease progression. The R-mNHL-BFM-90 treatment resulted in no need to assign second-line regimens. At the first stage, the efficacy of the compared induction therapy regimens was assessed. The next stage of the pharmacoeconomic study sought to analyze only the direct medical costs associated with the whole chemotherapy process. Further, the cost-effectiveness analysis was carried out, which allowed to estimate the financial resources necessary to achieve 1 case of complete remission (CR). A pharmacoeconomic decision-tree model was developed.

Results. CR was achieved in all 8 patients (100 %) who received the R-mNHL-BFM-90 block treatment. In the R-DA-EPOCH group CR was achieved only in 9 (64 %) out of 14 patients. The total mean cost of achieving 1 CR case per patient at all stages of diagnosis and chemotherapy with account for bed turnover (induction, second-line therapy, total supportive care) using R-mNHL-BFM-90 was 1,640,757 rubles, whereas in the R-DA-EPOCH group it was 1,469,878 rubles per patient. However, cumulative treatment costs of R-DA-EPOCH including chemotherapy of the second and further lines and supportive care were 2,896,519 rubles which exceeded those in the R-mNHL-BFM-90 group. Due to its higher efficacy the R-mNHL-BFM-90 immunochemotherapy precludes additional costs associated with both chemotherapy of the second and further lines and supportive care.

Conclusion. R-mNHL-BFM-90 as intensive induction block immunochemotherapy for DLBCL patients with poor prognosis is more effective than R-DA-EPOCH and allows to considerably reduce cumulative costs. It is possible due to complete preclusion of the costs of second-line chemotherapy and supportive care including blood component transfusions.

Keywords: diffuse large B-cell lymphoma, pharmacoeconomic analysis, cost-effectiveness analysis.

Received: March 26, 2021

Accepted: June 13, 2021

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Value of PD-L1 Protein Expression in the Combined Prognostic Model of Diffuse Large B-Cell Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA ,

SV Samarina1, NYu Semenova2, NV Minaeva1, DA Dyakonov1, VA Rosin1, EV Vaneeva1, 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 Valerevna Samarina, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(8332)25-46-88; e-mail: samarinasv2010@mail.ru

For citation: Samarina SV, Semenova NYu, Minaeva NV, et al. Value of PD-L1 Protein Expression in the Combined Prognostic Model of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2021;14(3):308–14. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-308-314

ABSTRACT

Aim. To study the value of PD-L1 protein expression in the combined model of diffuse large B-cell lymphoma (DLBCL) after administration of R-СHOP induction immunochemotherapy.

Materials & Methods. A retrospective analysis was based on the data of 85 DLBCL patients. The median age was 59 years (Q1–Q3: 29–83). Each patient received at least 2–6 courses of R-СHOP immunochemotherapy. The median follow-up period was 17 months. The optimal cut-off threshold for assessing the proportion of tumor cells expressing PD-L1 protein was determined by the САRT (Classification and Regression Tree) method.

Results. Patients were divided into three groups depending on IPI (International Prognostic Index) risk and immunohistochemical subtype (Hans algorithm) using CART. In group 1 with immunohistochemical GCB subtype and any IPI risk, except for the high one, low PD-L1 expression measured in terms of the DLBCL expressing tumor cell count, was identified in 21 (84 %) patients, 4 (16 %) patients showed overexpression. In case of low PD-L1 expression the 2-year progression-free survival (PFS) was 76 % (median not reached). In 4 patients with protein overexpression, the life duration after DLBCL diagnosed was 4, 16, 2, and 6 months, respectively. In group 2 with immunohistochemical non-GCB subtype and any IPI risk, except for the high one, 27 (67.5 %) patients showed low, and 13 (32.5 %) patients showed high PD-L1 expression. The analysis of the 2-year PFS resulted in no significant differences in groups with different relative counts of РD-L1 expressing tumor cells, i.e., 46 % and 49 %, respectively (p = 0.803). In case of low (< 24.5 % tumor cells) PD-L1 expression, the 2-year overall survival (OS) was better than in patients with overexpression (≥ 24.5 % tumor cells), i.e., 87 % vs. 52 %, respectively (p = 0.049). In group 3 with IPI high risk irrespective of immunohistochemical subtype, the proportion of PD-L1 expressing cells was higher than cut-off threshold (≥ 24.5 %) in 9 (45 %) patients, low protein expression was identified in 11 (55 %) patients. Deaths were reported in all patients of group 3 showing PD-L1 overexpression. In case of low protein expression the proportion of patients alive was 46 % (p = 0.002). None of the patients with high PD-L1 expression lived longer than 2 years. In those with low PD-L1 expression the 2-year OS was 66 % (p = 0.008).

Conclusion. Overexpression of PD-L1 by DLBCL tumor cells together with high IPI progression risk and non-GCB tumor subtype is associated with the worst OS and PFS. It can probably be accounted for by insufficient efficacy of R-СHOP induction immunochemotherapy in patients with high IPI risk. With this presumption, the PD-L1 expressing tumor cell count can be regarded as an important additional criterion for stratification of DLBCL patients into risk groups. Adding this new parameter to already established ones would probably contribute to differentiated approach to the choice of chemotherapy strategy at the onset of this aggressive lymphoma.

Keywords: diffuse large B-cell lymphoma, PD-L1 expression, overall survival, progression-free survival.

Received: January 29, 2021

Accepted: May 15, 2021

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Статистика Plumx английский

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Immunohistochemical Subtype and Parameters of International Prognostic Index in the New Prognostic Model of Diffuse Large B-Cell Lymphoma

LYMPHOID TUMORS , , , ,

SV Samarina1, AS Luchinin1, NV Minaeva1, IV Paramonov1, DA D’yakonov1, EV Vaneeva1, VA Rosin1, 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; Tel.: +7(912)732-47-56; e-mail: samarinasv2010@mail.ru

For citation: Samarina SV, Luchinin AS, Minaeva NV, et al. Immunohistochemical Subtype and Parameters of International Prognostic Index in the New Prognostic Model of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019;12(4):385–90 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-385-390

ABSTRACT

Aim. To develop an integrated prognostic model of diffuse large B-cell lymphoma (DLBCL) on the basis of immunohistochemical tumor subtype and parameters of International Prognostic Index (IPI).

Materials & Methods. Out of 104 DLBCL patients in the data base 81 (77.9 %) met the eligibility criteria. Median age was 58 years (range 23–83). All patients were treated with R-СНОР. The creation of overall survival (OS) prognostic model for DLBCL patients was based on machine learning with classification and regression trees. OS was analyzed using Kaplan-Meier method. Survival curves were compared by means of log rank test and hazard ratio (HR). Any test was considered significant if two-sided level of p < 0.05 was reached.

Results. Following the developed model three groups of patients were identified: the 1st group of low risk (the combination of low, intermediate-low, and intermediate-high risks according to IPI and GCB subtype); the 2nd group of intermediate risk (the combination of low, intermediate-low, and intermediate-high risks according to IPI and non-GCB subtype); the 3d group of high risk (irrespective of subtype). In the group of low risk (n = 26) 2-year OS during the monitoring period was 100 %. In the group of intermediate risk (n = 34) median OS was not reached, 2-year OS was 74 %, and expected 5-year OS was 68 %. In the group of high risk (n = 21) median OS was 25 months, 2-year OS was 46 %, and expected 5-year OS was 37 % (log rank p < 0.0001). HR calculated for the high-risk group compared with the low- and intermediate-risk groups was 5.1 (95% CI 2.1–12.1; p = 0.0003).

Conclusion. A new integrated system of DLBCL prognosis is suggested which includes IPI risk parameters and immunohistochemical subtype based on Hans algorithm. This prognostic system can be used in clinical practice for DLBCL patient stratification and risk-adapted therapy.

Keywords: diffuse large B-cell lymphoma, overall survival, prognosis, International Prognostic Index, machine learning.

Received: March 18, 2019

Accepted: August 27, 2019

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Primary Bone Lymphomas: Long-Term Results of a Prospective Single-Center Trial

LYMPHOID TUMORS , ,

AK Smol’yaninova, NG Gabeeva, VE Mamonov, SA Tatarnikova, LG Gorenkova, DS Badmadzhapova, AM Kovrigina, EG Gemdzhian, EE Zvonkov

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

For correspondence: Anna Konstantinovna Smol’yaninova, MD, PhD, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(495)612-23-61, +7(926)912-31-16; e-mail: annmo8@mail.ru

For citation: Smol’yaninova AK, Gabeeva NG, Mamonov VE, et al. Primary Bone Lymphomas: Long-Term Results of a Prospective Single-Center Trial. Clinical oncohematology. 2019;12(3):247–62 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-247-262

ABSTRACT

Background. Primary bone lymphomas (PBL) are rare extranodal lymphomas. In more than 90 % of cases they are reported as diffuse large B-cell lymphomas (DLBCL). At local (IE) stage of PBL the standard R-CHOP immunotherapy demonstrates efficacy over 90 %. If, however, such poor prognostic factors (PPF) as multiple bone lesions (IVЕ stage), increased lactate dehydrogenase (LDH) activity, B-symptoms, and large tumor mass are identified, R-CHOP efficacy tends to decrease. There is currently no optimal regimen for treatment of PBL patients with PPF. We suggest intensified multi-agent chemotherapy for this category of patients.

Aim. To assess long-term results of prospective single-center trial on the use of high-dose mNHL-BFM-90 program in patients with primary bone DLBCL and PPF.

Materials & Methods. The trial included 33 patients with primary bone DLBCL followed-up at the National Medical Hematology Research Center from 2006 to 2018. The median age of patients was 44 years (range 16–78 years). The spectrum of assessed data included main clinical, laboratory, X-ray and MRI tumor characteristics as well as survival rates and prognostic factors.

Results. PPF were identified in 29 (88 %) patients, out of them 20 (61 %) patients had an advanced stage (˃ IE), 20 (59 %) patients showed an increased LDH activity, B-symptoms were identified in 15 (45 %) patients, and large tumor mass was reported in 23 (71 %) patients. High-dose antitumor treatment (mNHL-BFM-90) was administered in 27 out of 33 patients. Overall and progression-free survival within the period of 5 years was 92 %. None of PPF significantly influenced survival rates.

Conclusion. The use of high-dose mNHL-BFM-90 program in PBL with poor prognosis achieves long-term remissions in 92 % patients. We recommend mNHL-BFM-90 as a therapy of choice for PBL patients with poor prognosis.

Keywords: primary bone lymphoma, diffuse large B-cell lymphoma, high-dose intensified multi-agent mNHL-BFM-90 program.

Received: January 25, 2019

Accepted: May 12, 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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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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Non-Hodgkin’s Lymphomas in Children: 25-Year Clinical Experience

LYMPHOID TUMORS , , , , , ,

TT Valiev, AV Popa, AS Levashov, ES Belyaeva, NS Kulichkina, BV Kurdyukov, RS Ravshanova, GL Mentkevich

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

For correspondence: Timur Teimurazovich Valiev, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-98-69; e-mail: timurvaliev@mail.ru

For citation: Valiev TT, Popa AV, Levashov AS, et al. Non-Hodgkin’s Lymphomas in Children: 25-Year Clinical Experience. Clinical oncohematology. 2016;9(4):420–37 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-420-437

ABSTRACT

Background & Aims. Current polychemotherapeutic protocols based on differentiated and risk-adopted approaches permitted to consider non-Hodgkin’s lymphomas (NHL) potentially curable diseases although they had been considered fatal previously. The aim of this study is to summarize and analyze outcomes of NHL therapy over a 25-year period.

Methods. 246 patients were enrolled in the study. They were treated in the department of chemotherapy of hemoblastoses in the Scientific Research Institute of Pediatric Oncology and Hematology under the NN Blokhin Russian Cancer Research Center over the period of 25 years: from April 1, 1991, till June 1, 2016. B-NHL-BFM 90/95 protocols and a modified B-NHL-BFM 95 protocol (with rituximab) were used for B-cell NHLs (n = 130). Patients with lymphocytic leukemia (n = 75) were treated using ALL-mBFM 90/95 and ALL IC-BFM 2002 protocols. 21 patients with anaplastic large cell lymphomas (ALCL) received treatment according to the B-NHL-BFM 90/95 protocol, and 20 patients received the НИИ ДОГ-АККЛ-2007 protocol.

Results. Taking into account clinical and immunological characteristics of ALCL, the authors invented an original НИИ ДОГ-АККЛ-2007 protocol. Special attention was paid to potential modification of standard treatment regimens for B-cell NHL by adding rituximab. The article demonstrates the evolution in prescription of rituximab for B-cell NHL and possibilities for reduction of the total number of polychemotherapy cycles for late-stage tumors without deterioration of treatment outcomes.

Conclusion. The obtained results permit to conclude that introduction of achievements of oncoimmunology, molecular biology, and cytogenetics will become the basis for further modification of existing treatment options for NHL.

Keywords: Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, T- and B-cell lymphoblastic lymphomas, treatment, children.

Received: June 12, 2016

Accepted: June 17, 2016

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

LYMPHOID TUMORS , , , , , ,

TT Valiev, AV Popa, AS Levashov, ES Belyaeva, NS Kulichkina, BV Kurdyukov, RS Ravshanova, GL Mentkevich

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

For correspondence: Timur Teimurazovich Valiev, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel: +7(499)324-98-69; e-mail: timurvaliev@mail.ru

For citation: Valiev TT, Popa AV, Levashov AS, et al. Non-Hodgkin’s Lymphomas in Children: 25-Year Clinical Experience. Clinical oncohematology. 2016;9(4):420–37 (In Russ).

DOI: http://dx.doi.org/10.21320/2500-2139-2016-9-4-420-437

ABSTRACT

Background & Aims. Current polychemotherapeutic protocols based on differentiated and risk-adopted approaches permitted to consider non-Hodgkin’s lymphomas (NHL) potentially curable diseases although they had been considered fatal previously. The aim of this study is to summarize and analyze outcomes of NHL therapy over a 25-year period.

Methods. 246 patients were enrolled in the study. They were treated in the department of chemotherapy of hemoblastoses in the Scientific Research Institute of Pediatric Oncology and Hematology under the NN Blokhin Russian Cancer Research Center over the period of 25 years: from April 1, 1991, till June 1, 2016. B-NHL-BFM 90/95 protocols and a modified B-NHL-BFM 95 protocol (with rituximab) were used for B-cell NHLs (n = 130). Patients with lymphocytic leukemia (n = 75) were treated using ALL-mBFM 90/95 and ALL IC-BFM 2002 protocols. 21 patients with anaplastic large cell lymphomas (ALCL) received treatment according to the B-NHL-BFM 90/95 protocol, and 20 patients received the НИИ ДОГ-АККЛ-2007 protocol.

Results. Taking into account clinical and immunological characteristics of ALCL, the authors invented an original НИИ ДОГ-АККЛ-2007 protocol. Special attention was paid to potential modification of standard treatment regimens for B-cell NHL by adding rituximab. The article demonstrates the evolution in prescription of rituximab for B-cell NHL and possibilities for reduction of the total number of polychemotherapy cycles for late-stage tumors without deterioration of treatment outcomes.

Conclusion. The obtained results permit to conclude that introduction of achievements of oncoimmunology, molecular biology, and cytogenetics will become the basis for further modification of existing treatment options for NHL.

Keywords: Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma, primary mediastinal (thymic) large B-cell lymphoma, T- and B-cell lymphoblastic lymphomas, treatment, children.

Received: June 12, 2016

Accepted: June 17, 2016

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