ISSN 1866-8836
Клеточная терапия и трансплантация

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Volume 10, Number 3-4
12/01/2021
Volume 10, Number 3-4
Editor-in-Chief
Kulagin A. D. (St. Petersburg, Russia)
Co-Editors-in-Chief
Wagemaker G. (Rotterdam, Netherlands)
Zander A. R. (Hamburg, Germany)
Deputy Editor
Fehse B. (Hamburg, Germany)
Managing Editor
Chukhlovin A. B. (St. Petersburg, Russia)
Editorial Board
Aleynikova O. V. (Minsk, Belarus)
Borset M. (Trondheim, Norway)
Chechetkin A. V. (St. Petersburg, Russia)
Fibbe W. (Leiden, Netherlands)
Gale R. P. (Los Angeles, USA)
Galibin O. V. (St. Petersburg, Russia)
Hehlmann R. (Mannheim, Germany)
Hölzer D. (Frankfurt a.M., Germany)
Klimko N. N. (St. Petersburg, Russia)
Kolb H.-J. (München, Germany)
Kröger N. (Hamburg, Germany)
Lange C. (Hamburg, Germany)
Mamaev N. N. (St. Petersburg, Russia)
Mikhailova N. B. (St. Petersburg, Russia)
Moiseev I. S. (St. Petersburg, Russia)
Nagler A. (Tel-Aviv, Israel)
Nemkov A. S. (St. Petersburg, Russia)
Paramonov I. V. (Kirov, Russia)
Roumiantsev A. G. (Moscow, Russia)
Savchenko V. G. (Moscow, Russia)
Smirnov A. V. (St. Petersburg, Russia)
Uss A. L. (Minsk, Belarus)
Zubarovskaya L. S. (St. Petersburg, Russia)
In this Issue

Expert opinion

Review articles

Mutual influence of malignant cells and cellular microenvironment: prospects for manipulating tumour microenvironment with nanomaterials

Anna M. Malkova1,2, Sergei V. Ageev1,2, Abdelsattar O. E. Abdelhalim2,3, Oleg E. Molchanov4, Dmitrii N. Maistrenko 4, Konstantin N. Semenov1,2,4, Vladimir V. Sharoyko1,2,4

Clinical studies

Comparison of bortesomib-based induction regimens with other treatment modalities in patients with newly diagnosed systemic light chain amyloidosis ineligible for autologous stem cell transplantation

Olga V. Kudyasheva, Olga V. Pirogova, Valentina V. Porunova, Svetlana V. Tolstova, Anna G. Smirnova, Ivan S. Moiseev, Alexander D. Kulagin

Journey of a hematopoietic stem cell transplantation center through COVID-19 pandemic: one-year experience

Aleksandr A. Siniaev, Marina O. Popova, Yulia A. Rogacheva, Anna A. Spiridonova, Maria Y. Averyanova, Alexander L. Alyanskiy, Bella I. Ayubova, Elena V. Babenko, Evgenii A. Bakin, Ildar M. Barkhatov, Maxim P. Bogomolny, atiana A. Bykova, Alina A. Vitrischak, Maria D. Vladovskaya, Yulia Y. Vlasova, Alisa G. Volkova, Asmik G. Gevorgian, Tatiana L. Gindina, Oleg V. Goloshchapov, Kirill A. Ekushov, Maria A. Estrina, Natalia E. Ivanova, Maxim A. Kucher, Alexei B. Chukhlovin, Kirill V. Lepik, Inna V. Markova, Natalia B. Mikhailova, Elena V. Morozova, Anna A. Osipova, Olesya V. Paina, Dmitrii E. Pevtsov, Anna G. Smirnova, Alexandr N. Shvetsov, Lilia V. Stelmakh, Galina N. Stolbenko, Ludmila S. Zubarovskaya, Sergey N. Bondarenko, Ivan S. Moiseev, Alexander D. Kulagin

The effect of using pretransplant locoregional therapy on the outcome of liver transplantation for HCC patients

Mohamed Rabei Abdelfattah1, Mohamed A. Sharaan1, Mohamed S. Kamel1, Hussein Elsiesy2

Clinical case

A case of rare pediatric unclassified NK/T cell lymphoma

Andrey V. Kozlov1, Olga I. Bogdanova1, Asmik G. Gevorgian1, Egor V. Volchkov2, Anna V. Botina1, Vadim V. Baykov1, Elena V. Morozova1, Natalya B. Mikhailova1, Ludmila S. Zubarovskaya1

Experimental studies

Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats

Natalia N. Sudareva1,2, Olga М. Suvorova1, Dmitry N. Suslov3, Oleg V. Galibin2, Aleksandr D. Vilesov1,2

An optimized protocol for mouse bone marrow mesenchymal stromal cells isolation and culture

Dima Joujeh1, Abduljalil Ghrewaty1, Chadi Soukkarieh2, Adnan Almarrawi1, Jamal Abdul Naser Darwicha3

Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw

Anna V. Lysenko1, Andrey I. Yaremenko2, Vladimir M. Ivanov3, Sergey V. Strelkov3, Elizaveta A. Ivanova2

Expert opinion

Will new drugs cure acute myeloid leukaemia?

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Robert Peter Gale MD

Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, UK


Correspondence:
Robert Peter Gale MD, PhD, DSc (hc), FACP, FRCPI (hon), FRSM, Centre for Haematology Research, Department of Immunology and Inflammation, Imperial College London, London, UK SW7 2AZ
Phone: +1 908 656 0484
Fax: +1 310 388 1320
E-Mail: robertpetergale@alumni.ucla.edu

Citation: Gale RP. Will new drugs cure acute myeloid leukaemia? Cell Ther Transplant 2021; 10(3-4): 4-7.

There are many new therapies approved to treat acute myeloid leukaemia (AML) including conventional and targeted drugs, and immune therapy. Most improve diverse outcomes including event- and relapse-free survivals and survival. However, most effect sizes are small and failure rates by 2 years are high. Based on the data reviewed above I conclude: (1) many new AML therapies target specific AML sub-types; (2) none are proved better than intensive radiochemotherapy in persons who could receive either therapy; (3) there is disagreement defining who can or cannot receive intensive therapy; (4) there are important problems with several new drug approvals; (5) azacitidine and venetoclax may be the new standard-of-care in elderly persons with AML judged unable to receive intensive therapy; and (6) new drugs are welcome but have not had a big impact on long-term survival of most people with AML.

Keywords

Acute myeloid leukemia, targeted therapy, efficiency.

Review articles

Liver transplantation in the treatment of ornithine transcarbamylase deficiency

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Jingya Wei, Bo Hui

Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, China


Correspondence:
Dr. Jingya Wei, Department of Neurology, Xijing Hospital, Fourth Military Medical University, 15 Changle-xi Road, Xi’an 710032, Shaanxi province, China
Phone: +86 29 8477 1055
E-mail: iamtrn@126.com


Citation: Wei J, Hui B. Liver transplantation in the treatment of ornithine transcarbamylase deficiency. Cell Ther Transplant 2021; 10(3-4): 26-29.

Ornithine transcarbamylase deficiency (OTCD) is a genetic disorder causing disturbed urea metabolic cycle with a high mortality rates. It’s a genetic metabolic disease manifesting as hyperammonemia. Drugs and hemodialysis may reduce blood ammonia levels in the patients. Liver transplantation may improve the long-term survival rate of patients, but it cannot reverse the nervous system damage that has occurred before, and cannot improve cognition. If the liver transplant is performed early in childhood, neurodevelopment may be normal at later terms. Late-onset patients should also be transplanted when required. Heterozygosity for OTCD in the donor is still risky and should only be used when there are no other options. Hepatocyte transplantation can be tried if necessary. Prevention of infection, long-term monitoring of liver function and blood ammonia are required posttransplant. Liver transplantation should be considered for all patients with genetic OTCD. The final decision of whether and how to use this treatment mode depends on individual clinical circumstances.

Keywords

Ornithine transcarbamylase deficiency, urea cycle disorder, liver transplantation, hepatocyte transplantation.

Review articles

Possible role of intestinal human viruses and bacteriophages following hematopoietic stem cell transplantation: a mini-review

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Oleg V. Goloshchapov1, Alexei B. Chukhlovin1,2, Oleg S. Glotov2

1 RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, St. Petersburg, Russia
2 Children's Scientific and Clinical Center for Infectious Diseases of the Federal Medical and Biological Agency, St. Petersburg, Russia


Correspondence:
Dr. Alexei B. Chukhlovin, RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, 6-8 L. Tolstoy St, 197022, St. Petersburg, Russia
Phone: +7 (921) 325-00-94
E-mail: alexei.chukh@mail.ru


Citation: Goloshchapov OV, Chukhlovin AB, Glotov OS. Possible role of intestinal human viruses and bacteriophages following hematopoietic stem cell transplantation: a mini-review. Cell Ther Transplant 2021; 10(3-4): 19-25.

Gut microbiota (a complex community of bacteria, fungi and viruses) is a dynamic biological system adapted for co-existence and symbiosis with host organism. Composition and ratio of bacterial populations is severely impaired in severe colitis and graft-versus-host disease (GVHD) occurring after hematopoietic stem cell transplantation (HSCT), especially, upon development of antibiotic-resistant bacterial strains. In contrast to the well-known bacterial microbiota studied by classic bacteriology and 16S rRNA gene sequencing, the viral populations of intestinal microbiota (e.g., bacteriophages) in are poorly studied in these clinical conditions, due to absence of a common viral gene suitable for comparative molecular genetic analysis. Assessing the ratios for viral and bacterial intestinal microbiota is feasible by means of metagenomic methods assaying multiple DNA species in the samples of biomaterial. As an object of clinical research, the patients with infectious complications caused by massive antibacterial and cytostatic treatment. Special attention should be drawn to severe colitis with C.difficile infection and antibiotic-resistant K.pneumonia and other pathogens with/without fecal microbiota transplantation (FMT). Conventional assessment of intestinal microbiota will be accomplished by next-generation sequencing (NGS) based on 16S rDNA gene diversity for bacterial genes, and metagenomic NGS analysis, in order to assess the ratio of various viruses of eukaryotic cells and, in particular, bacteriophages in cases of gut dysbiosis. Typical disturbances of the gut virome should be established, as well as role of bacteriophages in emergence of antibiotic-resistant intestinal bacteria after intensive antibiotic and chemotherapy.

Keywords

Intestinal microbiota, gut microbiota, viruses, bacteriophages, transplantation, immune complications, antibiotic resistance, NGS sequencing, 16S rRNA gene, metagenomics.

Review articles

Mutual influence of malignant cells and cellular microenvironment: prospects for manipulating tumour microenvironment with nanomaterials

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Anna M. Malkova1,2, Sergei V. Ageev1,2, Abdelsattar O. E. Abdelhalim2,3, Oleg E. Molchanov4, Dmitrii N. Maistrenko 4, Konstantin N. Semenov1,2,4, Vladimir V. Sharoyko1,2,4

1 Pavlov University, St. Petersburg, Russia
2 Institute of Chemistry, St. Petersburg State University, Saint Petersburg, Russia
3 National Center for Social and Criminological Research, Giza, Arab Republic of Egypt
4 A. M. Granov Russian Research Centre for Radiology and Surgical Technologies, St. Petersburg, Russia


Correspondence:
Dr. Vladimir V. Sharoyko, Pavlov University, 6-8 L. Tolstoy St., 197022, St. Petersburg, Russia
Phone: +7 (981) 936-41-51
E-mail: sharoyko@gmail.com


Citation: Malkova AM, Ageev SV, Abdelhalim AOE et al. Mutual influence of malignant cells and cellular microenvironment: prospects for manipulating tumour microenvironment with nanomaterials. Cell Ther Transplant 2021; 10(3-4): 8-18.

Development and progression of neoplasia occurs in parallel with changes in the surrounding stroma. Cancer cells may functionally reshape their microenvironment by secreting various cytokines, chemokines and generation of acidic medium. These factors contribute to differentiation of immune cells into immunosuppressive phenotype, stimulate the synthesis of a number of amino acid metabolism enzymes, growth factors, adhesion molecules, which promote invasion, angiogenesis and metastasis, and also reduce efficiency of anticancer drugs and radiation therapy. To increase effectiveness of the chemotherapy, multitargeted carbon nanomaterials may be applied. In particular, nanomaterials based on modified graphene make it possible to create multicomponent therapeutic constructs, including macromolecules, polymers, and effector agents. Initial experiments with unmodified graphenes demonstrated their toxicity associated with their accumulation in parenchymal organs and initiation of inflammatory processes. In the past few years, a series of works has been published in which the possibility of reducing the toxicity of graphene oxide through functionalisation has been demonstrated. This review summarises the experimental data on the creation of covalent and non-covalent conjugates based on graphene oxide and demonstrates their in vitro efficacy on various tumour cell lines. Separately, there are few data on the effect of nanomaterials based on graphene oxide on the tumour microenvironment.

Keywords

Tumour, microenvironment, progression, cytokines, acidosis, immune system, carbon nanomaterials.

Clinical studies

Comparison of bortesomib-based induction regimens with other treatment modalities in patients with newly diagnosed systemic light chain amyloidosis ineligible for autologous stem cell transplantation

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Olga V. Kudyasheva, Olga V. Pirogova, Valentina V. Porunova, Svetlana V. Tolstova, Anna G. Smirnova, Ivan S. Moiseev, Alexander D. Kulagin

RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, St. Petersburg, Russia


Correspondence:
Dr. Olga V. Kudyasheva, RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, 6-8 L. Tolstoy St, 197022, St. Petersburg, Russia
E-mail: bmt.myeloma@gmail.com


Citation: Kudyasheva OV, Pirogova OV, Porunova VV. Comparison of bortesomib-based induction regimens with other treatment modalities in patients with newly diagnosed systemic light chain amyloidosis ineligible for autologous stem cell transplantation. Cell Ther Transplant 2021; 10(3-4): 38-45.

Systemic light chain (AL) amyloidosis is a form of plasma cell disorders, characterized by overproduction of immunoglobulin light chains by clonal plasma cells and their deposition in organs and tissues as an insoluble fibrillar protein-amyloid. Suppression of amyloid production is the main goal of therapy, whereas cardiac involvement is the main predictor of survival. Therapeutic regimen containing bortezomib, cyclophosphamide and dexamethasone (CyBorD) was recently introduced as the standard of care for newly diagnosed patients. However, there are only few longitudinal comparative studies of this regimen with evaluation of organ responses.

In our study we analyzed the response to induction therapy in 105 patients with newly diagnosed patients with systemic AL amyloidosis ineligible for autologous stem cell transplantation (ASCT). All the patients were divided into three groups: group 1 received CyBorD; group 2 was treated with other bortezomib-based regimens, and group 3 received bortezomib-free regimens.

The 3-year OS was 70.3% (95% СI 61-80) with the median follow-up of 27.8 months (22 days to 11 years). Unfavorable factors for OS were as follows: age >70 years (p=0.007), male gender (p=0.015), Mayo stage IIIb (p=0.07) and renal damage stage III (p<0.0001). In the multivariate analysis, all other treatments than CyBorD were associated with decreased 3-year OS values (HR 4.9, 95% CI 1.4-17.2, p=0.012). 3-year progression-free survival (PFS) in CyBorD group was 79% (95% CI 63-95), vs 48% (95% CI 35-61) in group 2, and 55% (95% CI 30-80) in group 3 (p=0.28). Overall response rate (ORR) was 70% (n=74). The percentage of patients who showed hematological response was significantly higher in the CyBoRD group, 94% vs 84% in group 2 and 63% in group 3 (p=0.033), and median time to response in this group was 9.6 (5.3-15) months. The organ response (OR) was assessed over a 3-year period. The percentage of heart and renal responses was higher in CyBorD group. For cardiac responses, the rate was 78% vs 55% vs 16% (p=0.05) for groups 1, 2 and 3 respectively. Renal responses were observed in 90% vs 92% vs 57% of the patients (p=0.01). Overall median time of hematologic response (median, 10 months) and renal response (median, 12 months) occurred earlier than cardiac and hepatic responses (median, 26 months).

In summary, our results are comparable with previously published studies, demonstrating faster hematological response and organ responses after CyBorD treatment, which is translated into improved overall survival. Organ responses were observed significantly later than hematologic response.

Keywords

Systemic AL amyloidosis, CyBoRD, bortezomib.

Clinical studies

Journey of a hematopoietic stem cell transplantation center through COVID-19 pandemic: one-year experience

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Aleksandr A. Siniaev, Marina O. Popova, Yulia A. Rogacheva, Anna A. Spiridonova, Maria Y. Averyanova, Alexander L. Alyanskiy, Bella I. Ayubova, Elena V. Babenko, Evgenii A. Bakin, Ildar M. Barkhatov, Maxim P. Bogomolny, atiana A. Bykova, Alina A. Vitrischak, Maria D. Vladovskaya, Yulia Y. Vlasova, Alisa G. Volkova, Asmik G. Gevorgian, Tatiana L. Gindina, Oleg V. Goloshchapov, Kirill A. Ekushov, Maria A. Estrina, Natalia E. Ivanova, Maxim A. Kucher, Alexei B. Chukhlovin, Kirill V. Lepik, Inna V. Markova, Natalia B. Mikhailova, Elena V. Morozova, Anna A. Osipova, Olesya V. Paina, Dmitrii E. Pevtsov, Anna G. Smirnova, Alexandr N. Shvetsov, Lilia V. Stelmakh, Galina N. Stolbenko, Ludmila S. Zubarovskaya, Sergey N. Bondarenko, Ivan S. Moiseev, Alexander D. Kulagin

RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, St. Petersburg, Russia


Correspondence:
Dr. Aleksandr A. Siniaev, RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transpantation, Pavlov University, 6-8 L. Tolstoy St., 197022, St. Petersburg, Russia
E-mail: drsiniaev@yandex.ru


Citation: Siniaev AA, Popova MO, Rogacheva YA et al. Journey of a hematopoietic stem cell transplantation center through COVID-19 pandemic: one-year experience. Cell Ther Transplant 2021; 10(3-4): 30-37.

Hematopoietic stem cell transplantation (HSCT) is a life-saving procedure for oncological, hematological and non-malignant disorders. Despite global trend for a decrease of transplantation activity in view of the COVID-19 pandemic, we tried to maintain it by taking preventive measures and optimizing infection control in our center.

Patients and methods

This is an observational study. We collected the performance data of our transplant center from April 2020 to July 2021, i.e., during two waves of the pandemic. The main objectives were to study the influence of COVID-19 pandemic on the workflow of the HSCT center, including morbidity among employees and HSCT recipients, as well as on the transplant activity.

Results

The first case of COVID-19 infection in St. Petersburg was recorded on March 8, 2020. On March 30, 2020, a national lockdown had been imposed in the Russian Federation. The second wave of COVID-19 started in October 2020. Weekly screening of staff and patients was the main diagnostic tool, in addition to the governmental requirements. In sum, a total of 21702 PCR tests for SARS-CoV-2 were performed over the study period. As for July 1, 2021, 69.7% of employees became immune to the virus, due to previous COVID-19 disease, or by vaccination. In 2020, we managed to perform 419 HSCT, including 136 autologous and 283 allogeneic transplants. For comparison, 415 HSCTs were carried out in 2019, with 144 autologous and 271 allogeneic transplants. In 2020, the HSC donorship was shifted towards unrelated donors from the Russian Registry and haploidentical donors. Incidence of COVID-19 among HSCT recipients between April 2020 and July 2021 was 7.3% (n=39), being 8.6% (n=31) after allogeneic HSCT, and 4.5% (n=8) following auto-HSCT. The median age of patients with COVID-19 was 27 years (4-66). The median term for the COVID-19 onset was 68 days post-transplant (-1 to +2093). In most patients – 29 (74.3%) the HCT CI comorbidity index at the time of transplantation was 0. The stem cell source were either peripheral blood stem cells (n=22, 56.4%), or bone marrow (n=17, 43.6%). Most of the patients achieved complete remission of the underlying disease at the time of HSCT (n=30, 76.9%). The overall 100-day survival rate among HSCT recipients since the diagnosis of the COVID-19 was 79.5% (95% CI 0.609 – 0.884). The mortality rate was 20.5% (n=8). The causes of death were as follows: COVID-19 – 50% (n=4); secondary infectious complications, 25% (n=2); relapse of the underlying disease, 12.5% (n=1); hemorrhagic complications, 12.5% (n=1). The 100-day cumulative incidence of transplant-related mortality (TRM) among all HSCT recipients was 7% (95% CI 0.9 – 0.95) and 8.7% (95% CI 0.88 – 0.93) in 2019 and 2020, respectively (p=0.35).

Conclusions

Due to preventive measures, regular PCR screening, as well as the use of donors from the Russian Registry or haploidentical donors, we managed to maintain HSCT activity at the same level. The COVID-19 morbidity of HSCT recipients was 7.3%, their mortality rate – 20.5%. In summary, the pandemic did not affect transplant-related mortality among the HSCT recipients in our center.

Keywords

Pandemic, COVID-19, SARS-CoV-2, HSC transplantation.

Clinical studies

The effect of using pretransplant locoregional therapy on the outcome of liver transplantation for HCC patients

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Mohamed Rabei Abdelfattah1, Mohamed A. Sharaan1, Mohamed S. Kamel1, Hussein Elsiesy2

1 Department of Surgery, University of Alexandria, Faculty of Medicine, Alexandria, Arab Republic of Egypt
2 Organ Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia


Correspondence:
Prof. Dr. Mohamed Rabei Abdelfattah. MD, Associate Professor of Surgery, Department of Surgery, Faculty of Medicine, University of Alexandria, AL Khartoum Square, Azzaritta, Alexandria, Arab Republic of Egypt, PO BOX 21544
Phone: 00201023061111 (mob.)
E-mail: Mohamad.rabie@gmail.com


Citation: Abdelfattah MR, Sharaan MA, Kamel MS, Elsiesi H. The effect of using pretransplant locoregional therapy on the outcome of liver transplantation for HCC patients. Cell Ther Transplant 2021; 10(3-4): 46-53.

Our objective was to assess impact of downstaging locoregional therapy (LRT) on outcome of HCC treated by liver transplantation (LTx), and to assess long-term outcomes of LTx for hepatocellular carcinoma (HCC) and factors affecting them.

Materials and methods

115 Adult patients underwent LTx as a treatment of HCC between August 2006 and December 2019. As dependent on pre-transplant downstaging LRT, the patients were divided in two groups as follows: group A, patients corresponding to Milan criteria for LTx (MC) who did not receive downstaging LRT prior to LTx; group B included patients beyond Milan criteria who received downstaging LRT pretransplant.

Results

Among the entire LTx group, the patient, graft, and tumor-free survival rates were 79.7%, 90.4% and 88.2% respectively. 73 patients had HCC classified within MC (63.5% of transplanted HCC patients), while the remaining 36.5% were beyond MC (42 patients). The HCC patients successfully downstaged to the values corresponding to MC criteria showed overall survival and recurrence-free survival comparable to those who were transplanted within MC without LRT. HCC recurrence significantly correlated with detectable vascular invasion and poor degree of tumor differentiation. Moreover, the both features were significantly related to patient survival. Conversely, the transplant criteria and tumor volume >115 cm3 did not show a significant relation to patient survival or tumor recurrence.

Conclusion

Our results confirm the importance of biological tumor criteria over the commonly adopted morphological criteria. LRT offers an opportunity to downstage HCC to the values which fit the Milan criteria, while selecting more biologically favorable tumors.

Keywords

Liver transplantation, hepatocellular carcinoma, locoregional therapy, Milan criteria.

Clinical case

A case of rare pediatric unclassified NK/T cell lymphoma

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Andrey V. Kozlov1, Olga I. Bogdanova1, Asmik G. Gevorgian1, Egor V. Volchkov2, Anna V. Botina1, Vadim V. Baykov1, Elena V. Morozova1, Natalya B. Mikhailova1, Ludmila S. Zubarovskaya1

1 RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, St. Petersburg, Russia
2 Dmitry Rogachev National Research Center, Moscow, Russia


Correspondence:
Dr. Andrey V. Kozlov, RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, L. Tolstoy St, 197022, St. Petersburg, Russia
E-mail: kozlovandrew1983@yandex.ru


Citation: Kozlov AV, Bogdanova OI, Gevorgian AG et al. A case of rare pediatric unclassified NK/T cell lymphoma. Cell Ther Transplant 2021; 10(3-4): 54-60.

The article presents a case report of rare unclassified peripheral T-cell lymphoma (PTCL) in a child. The disease was characterized by refractory course and addition of immune checkpoint inhibitors (ICI) to chemotherapy resulted in remission induction. The rationale for immunotherapy was presence of programmed cell death ligand 1 (PDL1) on the cells of tumor microenvironment. First remission was consolidated with autologous hematopoietic stem cell transplantation (HSCT), and second remission was followed by allogeneic HSCT. Post-transplant period was complicated by severe acute graft-versus-host disease (GVHD) successfully managed with ruxolitinib. To perform local control, intrathecal cytostatic therapy was used prior to HSCT and post-transplant. Three years after last transplantation, the patient is disease-free and GVHD-free, with overall good quality of life and only mild impairment of cognitive functions.

Keywords

Peripheral T-cell lymphoma, children, chemoimmunotherapy, hematopoietic stem cell transplantation.

Experimental studies

Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats

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Natalia N. Sudareva1,2, Olga М. Suvorova1, Dmitry N. Suslov3, Oleg V. Galibin2, Aleksandr D. Vilesov1,2

1 Institute of Macromolecular Compounds RAS, St. Petersburg, Russia
2 Pavlov University, St. Petersburg, Russia
3 Granov Russian Research Center of Radiology and Surgical Technologies, St. Petersburg, Russia


Correspondence:
Dr. Natalia N. Sudareva, Institute of Macromolecular Compounds RAS, St. Petersburg, Russia
E-mail: nnsas@mail.ru


Citation: Sudareva NN, Suvorova OM, Suslov DN et al. Dextran sulfate coated CaCO3 vaterites as the systems for regional administration of doxorubicin to rats. Cell Ther Transplant 2021; 10(3-4): 71-77.

Doxorubicin (DOX) is a water-soluble anthracycline antibiotic possessing high anti-cancer activity. It is possible to achieve decrease in DOX concentration in blood (below the cardiotoxic level) during therapy by forming a depot containing DOX delivery systems that provide prolonged release of the drug. To this purpose, porous calcium carbonate particles (vaterites) coated with polyanion (dextran sulfate) were used. Due to submicron sizes of carriers, they do not freely enter bloodstream. The toxic drug is distributed in the organism only after entering the blood due to release from the delivery systems. Upon intraperitoneal administration of the DOX-containing delivery systems to rats inoculated with Seidel hepatoma, an efficient DOX concentration has been achieved which inhibited tumor growth and reduced the amount of ascitic fluid. Time profiles of DOX release into bloodstream of healthy rats were studied by HPLC after intraperitoneal administration of 4 mg of DOX, using various delivery systems. The drug injected in the form of dextran sulfate coated submicron carbonate cores was released within two weeks, and its concentrations were under the toxicity levels. When the nano-sized DexS+DOX conjugate was used for the drug delivery, DOX was found in rat blood at significantly higher concentrations. Irrespective of drug concentration in plasma, the results of physical examination and autopsy of rats performed on day 21 after intraperitoneal administration of DOX by various delivery systems indicated the absence of any negative reactions in animals.

Keywords

Doxorubicin, drug delivery system, CaCO3, dextran sulfate, polymer-drug conjugate, blood plasma.

Experimental studies

An optimized protocol for mouse bone marrow mesenchymal stromal cells isolation and culture

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Dima Joujeh1, Abduljalil Ghrewaty1, Chadi Soukkarieh2, Adnan Almarrawi1, Jamal Abdul Naser Darwicha3

1 Department of Biotechnology Engineering, Faculty of Technical Engineering, University of Aleppo, Syria
2 Department of Animal Biology, Faculty of Sciences, Damascus University, Syria
3 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Arab International University, Syria


Correspondence:
Dr. Dima Joujeh, Department of Biotechnology Engineering, Faculty of Technical Engineering, University of Aleppo, Syria
E-mail: dimajoujeh@gmail.com


Citation: Joujeh D, Ghrewaty A, Soukkarieh C, et al. An optimized protocol for mouse bone marrow mesenchymal stromal cells isolation and culture. Cell Ther Transplant 2021; 10(3-4): 61-70.

Mesenchymal stromal cells (MSCs) have stimulated much interest in the scientific community. Mouse MSCs serve as an ideal tool to explore cell biology and therapeutic potential of MSCs. Therefore, establishment of optimal, standardized protocol for mouse MSCs isolation and culture is required. Our aim was to develop and describe an efficient, reliable, and easy-to-perform protocol for isolation and culture of mouse bone marrow mesenchymal stromal cells MSC(M). Our protocol is based on a combination of flushing method and mechanical crushing of the bones. MSC(M) isolated using our protocol showed spindle-shaped appearance, positive expression of CD73 and CD44 markers, weak expression of CD34 and CD105, and negative expression for CD11b. They were also able to differentiate into mesodermal lineages such as adipocytes, and osteocytes. We hope that the data presented in this paper are of practical importance and can be used in clinical and research applications, and cell banking.

Keywords

Balb/c mice, bone marrow cells, isolation, mesenchymal stem cells, primary culture.

Experimental studies

Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw

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Anna V. Lysenko1, Andrey I. Yaremenko2, Vladimir M. Ivanov3, Sergey V. Strelkov3, Elizaveta A. Ivanova2

1 Department of Maxillofacial Surgery, Research Institute of Dentistry and Maxillofacial Surgery, St. Petersburg, Russia
2 Department of Maxillofacial Surgery, Pavlov University, St. Petersburg, Russia
3 Peter the Great St. Petersburg Polytechnic University, St. Petersburg, Russia


Correspondence:
Dr. Anna V. Lysenko, Department of Maxillofacial Surgery, Research Institute of Dentistry and Maxillofacial Surgery, Pavlov University, 44 Petrogradskaya Emb., 197101, St. Petersburg, Russia
Phone: +7 (812) 429-03-33
E-mail: lysenko.anna@mail.ru


Citation: Lysenko AV, Yaremenko AI, Ivanov VM et al. Experience in the use of a radio-oriented augmented reality navigation system for biopsy of a neoplasm of the lower jaw. Cell Ther Transplant 2021; 10(3-4): 78-83.

Radiomics is a quantitative approach to medical imaging that applies advanced mathematical analysis in order to improve the existing data available to clinicians. Radiomics quantifies texture information by mathematical extraction of spatial distribution of the signal intensities and pixel relationships. Quantitative evaluation of the texture 2-D information employs analytic techniques from the field of artificial intelligence. The data derived from radiographic images, when compared with clinical data, may potentially provide additional information aiming for support of decision-making in clinical medicine. In this study, a preliminary radiomic analysis of a lower jaw neoplasm was performed. Based on the data obtained, the optimal site for tissue biopsy was chosen. During diagnostic intervention, an augmented reality navigation system was used which took into account the results of the mentioned mathematical analysis.

Keywords

Radiomics, augmented reality, dynamic navigation systems, jaw neoplasms.