ISSN 1866-8836
Клеточная терапия и трансплантация

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Volume 10, Number 2
08/31/2021
Volume 10, Number 2
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

Obituary

In memory of Professor Valery Savchenko. January 8, 1952 – July 25, 2021

Alexander D. Kulagin, Rüdiger Hehlmann, Robert Peter Gale, Axel R. Zander, Boris Fehse

Review articles

Low-risk MDS: non-transplant therapeutic approach

Moshe Mittelman            

Clinical studies

Evaluation of BAALC- and WT1-expressing leukemic cell precursors in pediatric and adult patients with EVI1-positive AML by means of quantitative real-time polymerase chain reaction (RT-qPCR)

Nikolay N. Mamaev, Alyena I. Shakirova, Ildar M. Barkhatov, Mikhail M. Kanunnikov, Tatiana L. Gindina, Zhamal Z. Rakhmanova, Olesya V. Paina, Maria V. Latypova, Tatiana Yu. Gracheva, Ludmila S. Zubarovskaya

Autologous hematopoietic stem cell transplantation with low-intensity conditioning regimens in relapsing remitting multiple sclerosis: clinical outcomes and quality of life

Vladimir Y. Melnichenko1, Denis A. Fedorenko1, Tatiana P. Nikitina2, Natalia M. Porfirieva3, Ilya S. Nikolaev1, Tatiana I. Ionova2

Hematopoietic stem cell transplantation in acute myeloid leukemia from haploidentical donors compared with HLA-matched related donors

Renat S. Badaev, Darina B. Zammoeva, Diana V. Babenetskaya, Natalia A. Il’ina, Anastasia I. Reshetova, Larisa L. Girshova, Irina G. Budaeva, Elena N. Tochenaya, Raisa I. Vabishchevich, Alexey V. Petrov, Yulia A. Alexeeva, Andrey Yu. Zaritskey, Dmitry V. Motorin

Clinical case

Differential diagnosis of myelopathy in a patient with relapsed acute lymphoblastic leukemia

Alexey Yu. Polushin1, Ksenia S. Afanasyeva1, Bella I. Ayubova1, Sergey N. Bardakov2, Dmitry I. Skulyabin2, Andrey O. Agafonov1, Olga V. Sergiyenya3, Yaroslav B. Skiba1, Vladimir S. Krasnov1, Мikhail М. Кanunnikov1, Тatiana А. Rudakova1, Anna G. Smirnova1, Sergey N. Bondarenko1, Maria D. Vladovskaya1, Ivan S. Moiseev1, Alexander D. Kulagin1

Experimental studies

Specific aspects of the quality control strategy for biomedical cell products containing genetically modified human cells

Olga A. Rachinskaya, Ekaterina V. Melnikova, Marina A. Vodyakova, Vadim A. Merkulov

Rehabilitation

Obituary

In memory of Professor Valery Savchenko. January 8, 1952 – July 25, 2021

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Alexander D. Kulagin, Rüdiger Hehlmann, Robert Peter Gale, Axel R. Zander, Boris Fehse

Savchenko-1.jpg

Russian hematology has lost an esteemed leader, Professor Valery G. Savchenko who died suddenly on 25 July 2021. He was an outstanding physician, scientist and researcher. He headed the National Medical Research Center of Hematology, was Chief Hematologist of the Russian Health Ministry, President of National Hematology Society and Academician of the Russian Academy of Sciences. For many years he was responsible for advancing hematology in the USSR and later Russia.

Valery Savchenko was born in the Ukraine on 8 January, 1952. After graduation from the 2nd Moscow Physical and Mathematical School at Moscow University in 1969, he studied medicine at the 1st I. Sechenov Moscow Medical Institute graduating with distinction in 1975.

His life in medicine and research was devoted to hematology. In 1980, he completed his residency and postgraduate studies at the Department of Hematology and Intensive Care at the Central Institute of Postgraduate Education where he presented his MD thesis: Pathogenesis and treatment of idiopathic thrombocytopenic purpura. Thereafter, he joined the faculty as an Assistant Professor. In 1988, Dr. Savchenko moved with his mentor Prof. Andrei I. Vorobiov to the Research Centre for Hematology where he was appointed Head of the Hemoblastoses Chemotherapy and Bone Marrow Transplantation Department. In 1993, he presented his doctoral thesis: Modern strategy for acute leukemia therapy.

Dr. Savchenko was awarded the title of Full Professor in 1996. In 2011, he assumed the position of Director of the Hematology Research Centre, now National Medical Research Centre for Hematology of the Russian Ministry of Health. In 2004, he was elected a Corresponding Member of Academy of Medical Sciences, and in 2013 he became Academician of the Russian Academy of Sciences.

His inquiring mind, encyclopaedic knowledge and analytical thinking allowed him to excel in many areas of modern hematology. Prof. Savchenko was able to set forth distinct scientific tasks and resolve them, suggesting the direction of diagnostic evaluations and developing therapy algorithms.He evolved therapy protocols for acute leukemias and bone marrow failure disorders, headed the first Russian multi-centre studies, and, along with Prof. Boris Afanasyev, established and advanced hematopoietic cell transplants in the USSR and Russia.

Prof. Savchenko lead many studies in molecular genetics, biology, physiology of hematopoiesis, cytogenetics and transplant immunology and edited the Russian national guidelines for diagnosis and treatment of blood diseases. He had many pupils, several of whom are now leaders of hematology in Russia. Prof. Savchenko advised 30 PhD and 14 doctoral dissertations. He held or co-held 14 patents. He was very concerned with hematology education in Russia, was permanently engaged in educational activities and participated in interdisciplinary conferences.

Prof. Savchenko was Editor-in-Chief of Hematology and Transfusiology and on the Editorial Board of several academic journals including Therapeutic Archive, Hematology. Transfusiology Eastern Europe, Cellular Therapy and Transplantation, and Biological Products. Prevention, Diagnosis, Treatment.

Prof. Savchenko was a member of the World Committee of the International Association for Comparative Research on Leukemia and Related Diseases (IACRLRD) which he joined in the early 1990s on invitation by Prof. Rolf Neth and was on the World Committee as a Russian representative from 1997-2007 and again from 2015 onwards. In 2019, he was re-elected to serve on the World Committee until 2023. In 2021, he was invited to head as president the 31st IACRLRD symposium in Moscow in 2023.

Prof. Savchenko promoted participation of his Hematological Centre in the European LeukemiaNet (ELN); his institution becoming one of the six initial Russian ELN-participants. In 2011, he gave the ELN-keynote lecture on acute myeloid leukemia. His group continues to be a strong partner of cooperative leukemia research within ELN.

Analytical mind, soft speech and cautious humour of Prof. Savchenko’s are unforgettable. He is survived by his wife and long-term collaborator, Prof. Elena Parovichnikova, an internationally renowned hematologist, his son and daughter, Pavel and Sofia and grandchildren.

There are people that are hard to replace, and Savchenko was among them. We are reminded of the proverb: Death is a giant against whom even the Tsars must draw weapons. The loss is immense.

Alexander D. Kulagin, Prof., Director, RM Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transpantation, Pavlov University, St. Petersburg, Russia
Rüdiger Hehlmann, Prof. Dr., Dr. h.c, Med. Fakultät Mannheim, Heidelberg University, Germany
Robert Peter Gale, Visiting Prof., Dr., DSc h.c., Hematology Research Centre, Imperial College London, London, UK
Axel R. Zander, Prof. Dr. Dr. h.c., University Medical Center Hamburg-Eppendorf, Germany
Boris Fehse, Prof. Dr., Hamburg University, Germany

Review articles

Low-risk MDS: non-transplant therapeutic approach

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Moshe Mittelman            

Tel Aviv Sourasky Medical Center; Tel Aviv University, Israel


Correspondence
Prof. Dr. Moshe Mittelman, Professor of Internal Medicine and Hematology; Past Chairman, Department of Medicine, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University; Past President, Israel Society of Hematology and Transfusion Medicine.
Tel Aviv Sourasky (Ichilov) Medical Center, 6 Weizmann St, 64239, Israel.
E-mail: moshemt@gmail.com


A significant progress has been made over the last couple of decades in understanding the biology and treatment of myelodysplastic syndromes. Based on several parameters (% blasts, cytogenteics, number of affected lineages) the patients are classified as having a lower-risk (LR) or higher risk disease. Here, we will focus on LR-MDS.

The patients with LR-MDS are treated with RBC transfusions as needed, with or without erythroid stimulating agents. Luspatercept, an activin analogue, is a reasonable second line agent. Among the investigational agents in this field we can mention ruxodustat (a HIF inhibitor) and imetelstat, a telomerase inhibitor. Treatment of thrombocytopenia remain challenging and an open question.

Keywords

Myelodysplastic syndrome, low-risk, diagnostics, management, targeted therapy.

Review articles

What we are learning from CAR-T implementation: development, regulatory and clinical practices

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Mikhail Yu. Samsonov1, Andrey M. Lomonosov2

1 RPharm JSC; Department of Pharmacology, Institute for Pharmacy, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
2 Healthnet Working Group of National Technology Initiative, Moscow, Russia


Correspondence
Dr. Mikhail Yu. Samsonov MD, PhD, RPharm. Leninsky prospect 111, Moscow, Russia
E-mail: samsonov@rpharm.ru

The last decade has witnessed a significant advancement in medical science and technologies. The cell and gene therapies represent remarkable outcomes of such progress achieved in a very short timeframe. The COVID-19 pandemic has created roadblocks for patients to access hospitals for diagnosis and treatments since the onset of its first-wave. On the contrary, this one-year leap has witnessed unprecedented technological advances, especially in terms of mRNA-based therapies and their regulations. The present review focuses on CAR-T as a model with all key attributes and implications in complicated chains from early science to a variety of models and trends in clinical practice.

Keywords

Cell and gene therapy, CAR-T therapy, risk management plan, agile development approach.

Review articles

Practical review of current approaches to diagnosis and treatment of transplant-associated thrombotic microangiopathy

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Ivan S. Moiseev1, Tatyana G. Tsvetkova2, Tapani Ruutu3

1 RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, St. Petersburg, Russia
2 Nikiforov Russian Center of Emergency and Radiation Medicine, St. Petersburg, Russia
3 Clinical Research Institute, Helsinki University Hospital, Helsinki, Finland


Correspondence
Ivan S. Moiseev, PhD, MD, RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, 6-8 L Tolstoy St, 197022, St. Petersburg, Russia

Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare complication of hematopoietic stem cell transplantation with an endothelial damage being the major cause of clinical signs. Currently, four major set of diagnostic criteria exist which capture different populations of patients with variable severity of endothelial dysfunction and target organ involvement. Absence of widely excepted criteria for TA-TMA severity, outcome and response measures complicate the comparison of different treatment approaches. Withdrawal or tapering of calcineurin inhibitors is a widely excepted intervention; however, there are studies that indicate no benefit of this intervention in improving overall survival. Different strategies of substituting calcineurin inhibitors with other immunosuppressive may also have impact on survival in TA-TMA patients. Novel approaches in treatment include oligonucleotides and complement inhibitors. Indications for these treatments according to different diagnostic criteria are still to be defined. Currently published evidence highlight the need for cooperative effort to gather empirical data and harmonize definitions required for comparative clinical studies of novel agents.

Keywords

Thrombotic microangiopathy, hematopoietic stem cell transplantation, diagnostic criteria, calcineurin inhibitors, defibrotide, eculizumab.

Clinical studies

Evaluation of BAALC- and WT1-expressing leukemic cell precursors in pediatric and adult patients with EVI1-positive AML by means of quantitative real-time polymerase chain reaction (RT-qPCR)

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Nikolay N. Mamaev, Alyena I. Shakirova, Ildar M. Barkhatov, Mikhail M. Kanunnikov, Tatiana L. Gindina, Zhamal Z. Rakhmanova, Olesya V. Paina, Maria V. Latypova, Tatiana Yu. Gracheva, Ludmila S. Zubarovskaya

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


Correspondence
Prof. Nikolay N. Mamaev, RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov University, 12 Roentgen St, 197022, St. Petersburg, Russia
Phone: +7 (911) 760 5086
E-mail: nikmamaev524@gmail.com

Some basic biological and cytogenetic characteristics of leukemic cells in EVI1-positive (EVI1+) acute myeloid leukemia (AML) are shown to be different for pediatric and adult patients, like as their response to chemotherapy and hematopoietic stem cell transplantation (HSCT). Hence, one may also expect different pathogenetic roles of leukemic precursors in these AML variants. Our aim was to check this opportunity, and we have quantitatively assessed mRNA expression by leukemic precursors using a recently proposed BAALC/WT1 molecular panel. The levels of BAALC, WT1 and EVI1 gene expression were determined simultaneously in bone marrow samples from 8 pediatric and 6 adult patients with EVI1+ AML by means of quantitative real-time polymerase reaction (RT-qPCR) at specified time-points: a) upon primary diagnosis, b) prior to HSCT, and c) during post-transplant relapse (PTR). Blast cell counts were also provided for these bone marrow samples. Our study showed BAALC gene overexpression in both groups at all the tested stages. Before hematopoietic stem cell transplantation (HSCT) BAALC overexpression was revealed in 6 of 14 patients which could be associated with real difficulties for chemotherapy preparation for HSCT in this category of patients. Moreover, BAALC, or combined BAALC/WT1 overexpression were revealed in most patients with posttransplant relapse (PTR), thus suggesting a crucial role of BAALC-expressing precursors for the emerging relapses. Worth of note, BAALC overexpression was absent at all the tested stages of M3 and M7 FAB-variants, probably, due to more mature nature of appropriate precursor cells. In general, determination of BAALC- and WT1-expressing precursors by means of RT-qPCR seems to be a promising approach to the studies of precise pathogenetic mechanisms in different AML variants, as well as to diagnostics of emerging relapses and, thus, it may be quite important for clinical practice.

Keywords

Acute myeloid leukemia, EVI1-positive, pediatric, adults, hematopoietic stem cell transplantation, relapses, BAALC expression, WT1 expression, EVI1 expression, leukemic cell precursors, quantitative PCR.

Clinical studies

Autologous hematopoietic stem cell transplantation with low-intensity conditioning regimens in relapsing remitting multiple sclerosis: clinical outcomes and quality of life

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Vladimir Y. Melnichenko1, Denis A. Fedorenko1, Tatiana P. Nikitina2, Natalia M. Porfirieva3, Ilya S. Nikolaev1, Tatiana I. Ionova2

1 Pirogov National Medical and Surgical Center of The Ministry of Healthcare of Russian Federation, Moscow, Russia
2 Saint Petersburg State University Hospital, St. Petersburg, Russia
3 Multinational Center for Quality of Life Research, St. Petersburg, Russia


Correspondence
Professor Tatyana I. Ionova, Saint Petersburg State University Hospital, 154 Fontanka embankment, 190103, St. Petersburg, Russia
Phone: +7 (962) 710-17-11
E-mail: tation16@gmail.com

The effect of autologous hematopoietic stem cell transplantation (AHSCT) with low-intensity conditioning regimens, in terms of clinical and patient-reported outcomes, was studied in patients with relapsing-remitting multiple sclerosis (RRMS). In total, 258 RRMS patients were enrolled in a single-center study. The median follow-up duration was 30 months. Low-intensity conditioning regimens (two based on reduced BEAM and one on cyclophosphamide) were applied. Outcomes of AHSCT were evaluated from both the physicians’ and patients’ perspectives. Reversal of the disability progression, relapse-free survival (RFS), progression-free survival (PFS), as well as changes in quality of life (QoL), and severity of symptoms were analyzed. Transplantation procedure was well tolerated by the patients, and there were no cases of transplantation-related mortality. In addition, no deaths were registered throughout the follow-up period.

The vast majority of patients exhibited clinical improvement, or were in stable condition during the entire follow-up period. The estimated proportions of RFS and PFS were 83% and 86%, respectively, at 7 years after AHSCT. No differences in RFS were found between the patients who received reduced BEAM±ATG and high-dose cyclophosphamide+rituximab conditioning regimens. AHSCT resulted in significant and sustained QoL improvement, as well as decrease of symptom burden.The results of our study support feasibility of autologous HSCT with low-intensity conditioning regimens in RRMS. Multicentre cooperative studies should be done to optimize the treatment protocol of mini-AHSCT.

Keywords

Autologous hematopoietic stem cell transplantation, conditioning regimen, multiple sclerosis, clinical outcomes, quality of life.

Clinical studies

Hematopoietic stem cell transplantation in acute myeloid leukemia from haploidentical donors compared with HLA-matched related donors

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Renat S. Badaev, Darina B. Zammoeva, Diana V. Babenetskaya, Natalia A. Il’ina, Anastasia I. Reshetova, Larisa L. Girshova, Irina G. Budaeva, Elena N. Tochenaya, Raisa I. Vabishchevich, Alexey V. Petrov, Yulia A. Alexeeva, Andrey Yu. Zaritskey, Dmitry V. Motorin

V. A. Almazov National Medical Research Center, St. Petersburg, Russia


Correspondence
Dr. Dmitry V. Motorin, V. A. Almazov National Medical Research Center, 2 Akkuratova St, St. Petersburg, Russia
E-mail: dmotorin@mail.ru

Haploidentical SCT is an appropriate alternative for patients with acute myeloid leukemia (AML) in absence of compatible familial donor. Results of 57 haplo-SCT and 21 matched related donor SCT of patients with AML were assessed in the present study. Our aim was to compare clinical efficiency, complication rates and outcomes in the patients transplanted from related haploidentical donors versus HLA-compatible related donors. The rate of graft failure proved to be higher in haplo-SCT (10.6% and 0%, р=0.31) and cumulative frequency of platelet recovery was much lesser in haplo-SCT group (65.2% and 100%, р=0.00013). However, the time before recovery of granulocytopoiesis and thrombocytopoiesis was similar. Frequencies of acute GVHD, RFS and OS were comparable. In MRD-HSCT group was tendency for higher rate of chronic GVHD (9.0% and 22.9%, p=0.07) and relapse (40.7% and 16.6%, p=0.15).

Active disease was the only factor with negative influence on results of SCT. Haplo-SCT was associated with higher rate of D+30 (р=0.001) and 100-d (р=0.011) mortality. In the group of patients after haplo-SCT without early mortality, GVHD grade 3-4 had negative influence on results of SCT. Hence, haploidentical HSCT is a plausible alternative for AML patients if HLA-compatible donor is not available. In particular, best results are obtained when haplo-HSCT is performed in the 1st complete clinical remission.

Keywords

Acute myeloid leukemia, hematopoietic stem cell transplantation, related, haploidentical donor, HLA-compatible donor.

Clinical case

Differential diagnosis of myelopathy in a patient with relapsed acute lymphoblastic leukemia

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Alexey Yu. Polushin1, Ksenia S. Afanasyeva1, Bella I. Ayubova1, Sergey N. Bardakov2, Dmitry I. Skulyabin2, Andrey O. Agafonov1, Olga V. Sergiyenya3, Yaroslav B. Skiba1, Vladimir S. Krasnov1, Мikhail М. Кanunnikov1, Тatiana А. Rudakova1, Anna G. Smirnova1, Sergey N. Bondarenko1, Maria D. Vladovskaya1, Ivan S. Moiseev1, Alexander D. Kulagin1

1 Pavlov University, St. Petersburg, Russia
2 S. M. Kirov Military Medical Academy, St. Petersburg, Russia
3 V. A. Almazov National Medical Research Center, St. Petersburg, Russia


Correspondence
Dr. Alexey Yu. Polushin, Pavlov University, 6-8 L. Tolstoy St, 197022, St. Petersburg, Russia
Phone: +7 (911) 816 7559
E-mail: alexpolushin@yandex.ru

Leukemia-associated myelopathy is a rare but still underestimated complication. It can be of different etiology, associated with both underlying disease and its specific treatment. It requires differential diagnosis with funicular myelosis, polyradiculoneuropathy, volumetric and hemorrhagic masses, vascular ischemia, dysmetabolic manifestations, as well as with adverse effects of intensive treatment of the primary disease using irradiation, cytostatic, targeted therapy, with paraneoplastic myelopathy and progression of the underlying disease. However, its diagnostics by neuroimaging techniques may proceed later than the onset of appropriate neurological symptoms.

We present a clinical case of myelopathy in a 31-year-old patient with acute lymphoblastic leukemia (ALL) which was confirmed by MRI of the spinal cord 2.5 months after the onset of neurological signs. The article presents diagnostic criteria for ALL-associated myelopathy.

Keywords

Neuroleukemia, acute lymphoblastic leukemia, allogeneic hematopoietic stem cell transplantation, neurological complications, myelopathy, MRI, differential diagnosis, targeted therapy.

Experimental studies

Specific aspects of the quality control strategy for biomedical cell products containing genetically modified human cells

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Olga A. Rachinskaya, Ekaterina V. Melnikova, Marina A. Vodyakova, Vadim A. Merkulov

Scientific Centre for Expert Evaluation of Medicinal Products, Moscow, Russia


Correspondence
Ekaterina V. Melnikova, PhD; Scientific Centre for Expert Evaluation of Medicinal Products, 8/2 Petrovsky Blvd, Moscow 127051, Russia
E-mail: MelnikovaEV@expmed.ru

Regulatory authorities around the world have so far endorsed eleven products containing cells with a genome modified by a viral vector (VV) carrying the sequence of the target gene (ex vivo gene therapy cellular products, GTPs). These products (referred to as biomedical cell products, BMCPs, in accordance with Russian legislation) are intended for treatment of haemato-oncological diseases (using the technology of chimeric antigen receptors) and genetic hereditary diseases. Approval of production and marketing for such ex vivo GTPs is based on adequate and comprehensive assessment of their quality, which is challenging due to specific composition of these products that include both viable cells and viral genetic material. The aim of this study was to analyse international experience in quality assurance of ex vivo GTPs in order to identify specific aspects of their quality control strategy during development, production, and expert quality control as a part of the national authorisation procedures.

The data presented in public reports of the U.S. Food and Drug Administration (FDA) (Summary basis for regulatory action) and the European Medicines Agency (EMA) (Assessment reports) provided the basis for evaluation of quality control strategies used in the production and release control of approved ex vivo GTPs. The comparative analysis helped to identify specific features of quality control strategies used for these products upon control of raw and initial materials, creation and characterisation of cell banking systems, implementation of in-process and release controls, including development of specifications for active substances and final products, validation of the manufacturing process, stability studies during storage and transportation of active substances and final products. For instance, the use of VVs for transfection requires assessment of such quality attributes as insert integrity, quantitative titer, biological activity, purity and impurities (admixtures), bacterial endotoxins, biological burden, sterility, presence of potentially replication-competent viruses, etc. Transduction of viable cells, in its turn, requires quality control of medicinal products in terms of such quality attributes as viability and proportion of transduced cells (TCs), activity, purity, impurities, safety, and others. Due to specific nature of ex vivo GTP production which is a two-stage process (obtaining the vector at stage 1, and producing TCs and final product at stage 2) characteristic of all the products considered in the study, it seems reasonable to provide separate specifications for the active substance (viral vectors), and a general specification for the active substance (TCs) and the ready-to-use product. Test results for a number of parameters included into the final product specification could not be obtained at the stage of product inspection, but may be derived from earlier stages of production, or even during pre-clinical studies, upon validation of the manufacturing process as well as during the product development.

Keywords

Ex vivo gene therapy products, biomedical cell products, quality control, active substance, viral vector, transduced cells, specification, quality attributes.

Rehabilitation

Performance features of hospital nurses in multidisciplinary rehabilitation team for the patients undergoing cytostatic therapy and hematopoietic stem cell transplantation

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Natalia G. Saltykova, Maxim A. Kucher, Alisa G. Volkova, Galina N. Stolbenko

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


Correspondence
Natalia G. Saltykova, RM Gorbacheva Research Institute of Pediatric Oncology, Hematology and Transplantology, Pavlov University, 6-8 L.Tolstoy St, 197022, St. Petersburg, Russia
Phone: +7 (964) 395 3367
E-mail: nata.saltykova2014@yandex.ru

Efficiency of hematopoietic stem cell transplantation and accompanying therapy in the patients with hereditary and malignant diseases of blood system depends, e.g., on timely and sufficient treatment and rehabilitation programs. At all stages of the therapy performed, key role belongs to medical nurses. Therefore, education and training of highly skilled and motivated nursing staff is required, due to implementation of new specialty "medical nurse for rehabilitation" in Russia since 2020, arrangement of rehabilitation departments and centers with multidisciplinary medical teams (MRHT).

Keywords

Hematopoietic stem cell transplantation, rehabilitation, nursing care.