03/31/2017 08:23:00 am
Afanasyev B. V. (St. Petersburg, Russia)
Wagemaker G. (Rotterdam, Netherlands)
Zander A.R. (Hamburg, Germany)
Fehse B. (Hamburg, Germany)
Chukhlovin A. B. (St. Petersburg, Russia)
Aleynikova O. V. (Minsk, Belarus)
Borset M. (Trondheim, Norway)
Chechetkin A. V. (St. Petersburg, Russia)
Fibbe W. (Leiden, Netherlands)
Galibin O. V. (St. Petersburg, Russia)
Hölzer D. (Frankfurt a.M., Germany)
Klimko N. N. (St. Petersburg, Russia)
Kolb H.-J. (München, Germany)
Kröger N. (Hamburg, Germany)
Kulagin A. D. (St. Petersburg, Russia)
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)
The Journal founders:
University Medical Center Hamburg-Eppendorf (Germany);
St. Petersburg I. Pavlov State Medical University (Russia), and Foundation for Development of Bone Marrow Transplantation (St. Petersburg, Russia)
CTT Journal Archive:
The ongoing CTT issue concerns different topics of transplantology. A special editorial article written by Boris V. Afanasyev is dedicated to 70-year anniversary of Professor Alexander G. Roumiantsev, an outstanding Russian specialist in pediatric hematology. Under clinical articles, a study by Dr. Tatiana L. Gindina concerns adverse prediction value of complex leukemia cell karyotype. Number of such abnormalities per karyotype, such as stage of disease, proved to be independent prognostic factors in a mixed cohort of Ph+ patients with acute lymphoblastic leukemia at the moment of HSCT. The article combines different additional chromosomal aberrations in acute leukemia and describes them in details.
The next article by Maxim A. Kucher and colleagues presents and substantiates a popular theory on close ties between intestinal microbiota and clinical risks after hematopoietic stem cell transplantation. This hypothesis was inspired by distinct correlations between intestinal dysbiosis and clinical episodes of chronic inflammatory bowel diseases. Assessment of microflora biodiversity and prevalence of distinct bacterial species post-HSCT could be an important tool to assess microbial activation as a factor, e.g., of graft-versushost-disease. The authors present their initial data on fetal microflora transplantation in complicated HSCT cases, aiming to prevent or treat severe aGVHD.
A clinical report by Vadim M. Kemaikin et al. from Astana (Kazakh Republic) shares his experience of bone marrow transplant service at the basis of Astana Center for Urgent Medicine. Six years of development transformed a modest auto-BMT unit to a modern Department for different types of HSCT, including haploidentical grafting with rather good outcomes in the patients. Paroxysmal nocturnal hemoglobinuria (PNH), a clonal blood system membranopathy, is among conditions potentially treatable by BMT. To improve prognosis and quality of life in such patients and other conditions with PNH clone, one may use Eculizumab, a monoclonal antibody against complement component since its infusion may block intravascular complement-mediated RBC hemolysis. In her report, Galina A. Dudina has described an instructive case of PNH in an old patient with MDS, who was successfully treated with Eculizumab, since HSCT approach is not valid at old age, with a number of severe comorbidities.
Under experimental studies we would like to recommend a review by Marina O.Popova and colleagues who discuss potential clinical uses of gene editing for treatment of genetic disorders. The authors concern methodology of the in vitro targeted editing procedure using lentiviral vectors. Next, they delineate a spectrum of inherited monogenic disease which are under clinical trials for gene therapy which contains, e.g., such well-known disorders as primary immune deficiencies, beta-thalassemia etc.
The last short communication reflects a viewpoint by Kristina Khodova, an expert for immunogenetics and development of gene therapy, upon business outlooks of the gene therapy. The author reviews a variety of different approaches to gene therapy, appropriate patent stories, current and prospective investments into the studies.
Kristina A. Khodova
Professor Boris V. Afanasyev, Editor-in Chief “Cellular Therapy and Transplantation”, Director of R. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation, St. Petersburg
Alexander Grigoryevich graduated with honors from the Pediatric Faculty at the 2nd N. I. Pirogov Moscow State Medical Institute in 1971, and, in subsequent times, he was within the walls of the 2nd MOLGMI (since 1991 – Russian State Medical University, since 2011 – N. I. Pirogov Russian National Research Medical University). Over these years, А. G. Roumiantsev approved himself a highly qualified specialist in pediatrics, hematology/immunology, a skilled scientist and university professor. A gifted teacher who authored and co-authored several basic educational programs in children diseases, polyclinic pediatrics, pediatric hematology/oncology, immunology/allergology, transfusion medicine, scientific editor of some basic textbooks and teaching media in pediatrics, pediatric hematology and immunology.
Galina A. Dudina
Moscow Clinical Research Center, Moscow Health Department, Moscow, Russian Federation
CorrespondenceDudina Galina A., PhD (Medicine), Senior Research Associate, Department of Oncohematology and Secondary Immunodeficiencies, The Moscow Clinical Research Center of Moscow Health Department, Entusiastov Ave 86, 111123, Moscow, Russian Federation
Phone: +7 (916) 650 8577
Paroxysmal nocturnal hemoglobinuria (PNH) is a systemic, acquired clonal hematological disorder which results from loss of complement-inhibiting proteins (CD55 and CD 59) from the blood cell surface. Therefore, such patients develop chronic complement-mediated intravascular hemolysis, with thromboses manifesting as most severe clinical complications. Recommendations of International PNH groups discern certain risk groups based on detection of a pathological cell clone, including patients with myelodysplastic syndrome (MDS). Here we describe detection of a clinically sound PNH clone in an elderly patient with MDS, as well as positive results of patho-genetic treatment with Eculizumab.
Paroxismal nocturnal hemoglobinuria, myelodysplastic syndrome, diagnostics, Eculizumab
Marina O. Popova, Kirill V. Lepik, Vladislav S. Sergeev, Alena I. Shakirova, Alisa Y. Potter, Albert R. Muslimov, Ildar M. Barkhatov, Boris V. Afanasyev
Dr. Marina O. Popova, PhD, R. Gorbacheva Memorial Research Institute of Children’s Oncology, Hematology and Transplantation, The First Pavlov State Medical University of St. Petersburg, Russia, 12 Roentgen St., 197022, St. Petersburg, Russia
Phone: +7 (812) 233-29-25 (office), +7 (911) 711-39-77 (mobile) E-mail: email@example.com
KeywordsGenome editing, hematopoietic stem cells, ZFN, TALEN, CRISPR-Cas9, hematopoietic stem cell transplantation, HSCT, HIV, inherited diseases, monogenic diseases, cancer, hematological malignancies.
Kristina A. Khodova
Skolkovo Foundation, Moscow, Russia
Dr. Kristina A. Khodova, Skolkovo Innovation Center, Nobel Street 5, 143026, Moscow, Russia
Phone: +7 (916) 438-29-54
Recent improvements in targeted genome editing technologies have opened new potential therapeutic applications in different medical conditions. Despite the fact that most of these technologies are still at early implementation phase, they already demonstrate a high therapeutic potential which may change treatment methodology for many severe diseases, and exert a significant influence upon market landscape and human population in general. However, some major issues and risks remain in the field, i.e., whether appropriate products and results will meet expectations of scientists, engineers and investors, and what risks could be anticipated for the registration procedures and introduction of original products into clinical practice.
Genome editing, investment, startups, research & development, intellectual property.
Tatiana L. Gindina, Nikolai N. Mamaev, Elena S. Nikolaeva, Irina A. Petrova, Elena I. Darskaya, Olga V. Pirogova, Yana V. Gudozhnikova, Olesya V. Paina, Alexander L. Alyanskyi, Sergey N. Bondarenko, Ludmila S. Zubarovskaya, Boris V. Afanasyev
Patients and methodsWe have performed a retrospective analysis of treatment results for a mixed cohort of the patients with Ph+ ALL, including 19 children (aged 5 – 18 y.o.) and 46 adults (aged 19 – 57 y.o.) who received allo-HSCT at our Institute over 2008 to 2015. Among sixty-five subjects with Ph+ ALL, the results of standard cytogenetic studies were available for 53 patients.
ResultsThirty-three patients of 53 (51%) exhibited an isolated t(9;22) translocation. ACA were revealed in 20/53 patients (31%), including 13/53 (20%) subjects with 3 and more chromosome abnormalities. Chromosomes 1, 5, 7, 8, 9, 22 were most commonly affected with additional anomalies. Structural abnormalities attributable to ACA were imbalanced in 16 patients (80%), whereas only 4 patients (20%) showed balanced translocations. In a univariate analysis, significance was shown for the donor type (matched related and unrelated vs haploidentical, p=0.02), clinical stage at HSCT (1st remission vs other stages, p=0.01, for EFS only), additional chromosomal abnormalities (ACA-negative vs ACA-positive, p=0.04, for OS only), and, in particular, complex chromosomal aberrations (<3 anomalies vs ≥3 anomalies, p=0.01, for OS only). According to multivariate analysis, the number of additional chromosomal abnormalities per karyotype (HR 2.79, 95% CI 1.23-6.34; р=0.01, for OS only) and clinical stage at HSCT (HR 2.15, 95% CI 1.13-4.09; р=0.01, for EFS only) are independent prognostic factors for clinical outcomes.
ConclusionThe study has shown that complex chromosomal anomalies and the stage of disease at the moment of HSCT are independent prognostic factors in a mixed cohort of Ph+ ALL patients treated with hematopoietic stem cell transplantation.
KeywordsAcute lymphoblastic leukemia, Ph1-positive, allo-HSCT, additional chromosomal abnormalities.
Vadim M. Kemaikin, Anastasiya A. Olifirovich, Alexandr V. Kolesnev, Anatoliy V. Nemerovchenko, Ruzal F. Vildanova, Olga V. Gainutdinova, Adiya A. Tusipova, Ayauzhan E. Esimbekova, Aliya K. Baimursina, Ayzat S. Suleimenova, Olga O. Lesechko, Gulnaz D. Ansatbaeva, Mariya S. Alimbetova
Dr. Vadim M. Kemaikin, Chief, BMT Department, National Research Centre for Oncology and Transplantation, Kerey, Zhanibek Khanov st., 3, Astana, 010000, Republic of Kazakhstan
Phone: +7 7172 70 29 41 E-mail: firstname.lastname@example.org
KeywordsHematopoietic stem cell transplantation, clinical advancements, Astana, Republic of Kazakhstan.
Maxim A. Kucher, Oleg V. Goloschapov, Ivan S. Moiseev, Boris V. Afanasyev
Dr. Maxim A. Kucher, Head, Department of Clinical Nutrition, R. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation; The First State I. Pavlov Medical University, St. Petersburg, Russia, L. Tolstoy St. 6-8, 197022
Phone: 8 (812) 338 6260, +7 (921) 993 9902 E-mail: email@example.com