XV Raisa Gorbacheva Memorial Meeting Hematopoietic Stem Cell Transplantation. Gene and Cellular Therapy: An overview

The pre-congress day included industrial symposia devoted to the most urgent issues of drug therapy for a wide range of blood diseases and complications of HSCT, new aspects of patient care in the context of the COVID-19 pandemic.

Cell and Gene Therapy session (16 September, 2021) included a number of quite impressive and innovative reports. The keynote lecture was given by Prof. Hans-Peter Kiem (Seattle, USA) who reviewed current approaches to therapy of inherited disorders using gene modifications of autologous hematopoietic stem cells in order to obtain desirable correcting effect. Dr. Fedor Urnov (Berkeley, USA) presented a comprehensive summary of history and clinical outlooks for gene editing, arguing, mainly, for the CRISPR platform.

A competent overview of current diagnostic and therapeutic approaches in the field of genetic disorders was made by Prof. Sergey Kutsev (Moscow, Russia). Prof. Maria Ester Bernardo (Milan, Italy) and Dr. Tatyana Bykova (St. Petersburg, Russia) discussed current gene therapy options for these groups of patients. Prof. Gerard Wagemaker (Rotterdam, The Netherlands) remembered fundamental steps and historical facts on hematopoietic stem cell (HSC) transplantation, as a basis for development of current gene therapy with modified HSCs, primarily, in immune deficiencies and lysosomal storage diseases. Of special significance was the lecture by Prof. Giuliana Ferrari (Milan, Italy). The speaker described heterogeneous molecular pathology in beta-thalassemia and presented promising gene targets to correct hemoglobin synthesis. Results of pre-clinical studies and clinical prospective of gene therapy in hemophilia were discussed by Prof. Denise Sabatino (Philadelphia, USA).

Gene editing technologies for epigenomic modification were proposed by Prof. Claudio Mussolino (Freiburg, Germany) who presented his report in face-to-face format. The reported CAST-Seq approach may present a useful tool for detecting some off-target effects of gene editing procedures (Julia Klermund, Freiburg, Germany). Prof. Boris Fehse (Hamburg, Germany) shared his experience in TALEN application for CCR5-directed editing to produce HIV-resistant blood cells for potential clinical use. Dr. Alena Shakirova (St. Petersburg, Russia) reported some data on efficiency of CCR5 gene editing in hematopoietic cells for HIV therapy.

Most clinical studies in gene therapy concerned preparation and usage of CAR-T cells in treatment of lymphoblastic leukemia. General aspects of CART implementation were reported in the keynote lecture by Prof. Michel Sadelain (New York, USA). Prof. Michael Maschan (Moscow, Russia) reported his experience in CD19-directed CAR-T cells when treating pediatric patients with ALL and discussed regulatory problems with gene-modified cell products in Russia. Practical aspects of CAR-T cell preparation in clinical setting, processing and storage were presented by Dr. Isabelle Riviere (New York, USA), Juan Otero (Barcelona, Spain), Alexander Migas (Misk, Republic of Belarus), and Vladislav Sergeev (St. Petersburg, Russia). Some reports dealt with other CAR-T cell applications, e.g., GVHD induction capacity (Alexey Petukhov, St. Petersburg, Russia), and their prospects in treatment of viral infections (Grigory Efimov, Moscow, Russia).

A special session was dedicated to regulations and legislation for the medicinal manipulated cell products, including CAR-T cells. An interesting essay tracing the ways from the idea of gene therapy to clinical implementation was presented by Kristina Zakurdaeva (Moscow, Russia). The details of sophisticated Russian regulation in the field of medicinal cell products and their licensing procedure were presented and discussed in the reports by Mikhail Samsonov, and Ekaterina Melnikova (Moscow, Russia). In general, the session proceeded quite successfully, with many questions asked and vivid final discussion.

The plenary session on September 17 was opened by the ceremony of Doctor Honoris Causa award to Professor Dieter Hoelzer (Frankfurt/Main, Germany) whose merits in leukemia chemotherapy and HSCT are recognized worldwide. His lecture concerned novel treatment approaches based on modern drugs and monoclonal antibodies against lymphoblastic cells. The B. V. Afanasyev Memorial Lecture presented by Prof. Elena Semenova (St. Petersburg, Russia) cove- red various aspects of pediatric HSCT, being dedicated to the 30th anniversary of the first pediatric HSCT in Russia. Professor Robert Gale has discussed recent clinical results in resistant AML therapy, which still remain suboptimal, even with novel targeted drugs. The comprehensive lecture by Prof. Nicolaus Kroeger (Hamburg, Germany) highlighted efficiency and safety of haploidentical HSCT when applying optimal protocols of GVHD prevention. Professor Anna Sureda (Barcelona, Spain) provided update of current studies concerning long-term outcomes in Hodgkin lymphoma combining conventional protocols and novel therapies.

A special session was dedicated to therapeutic options in acute leukemia, including curative potential of HLA-matched HSCT (Prof. Andrea Bacigalupo, Rome, Italy), and general efficiency of allo-HSCT for long-term survival in AML relapses, as reported by Prof. Dietger Niederwieser (Leipzig, Germany) in a lecture based on several German trials. Meanwhile, Dr. Sergey N. Bondarenko (St. Petersburg, Russia) confirmed this viewpoint by clinical experience obtained by CIC 725 team with multimodal AML therapies.

Prof. Elena Parovichnikova (Moscow, Russia) highlighted pivotal role of minimal residual disease (MRD) values for planning ongoing therapies in acute lymphoblastic leukemia (ALL). Prof. Robin Foa (Rome, Italy) discussed current data on clinical efficiency of well-known tyrosine kinase inhibitors (TKI) in Ph-positive ALL patients.

The results of allogeneic HSCT and the role of minimal residual disease (MRD) after HSCT in pediatric patients with acute myeloid leukemia not in remission were shown by Prof. Alexey Maschan (Moscow, Russia). Efficiency of GVHD prophylaxis by post-transplant cyclophosphamide after haplo-HSCT was confirmed by Dr. Dmitry Motorin (St. Petersburg, Russia).

A session “Chronic hematological malignancies” started with a lecture by Prof. Moshe Mittelman (Tel Aviv, Israel) who presented an update of novel treatment strategies in low-risk myelodysplastic syndrome (MDS). Dr. Nikolay Tcvetkov (St. Petersburg, Russia) discussed different prognostic factors in high-risk MDS. Distinct benefits of HSCT in high-risk MDS cases were reported by Dr. Larisa Kuzmina (Moscow, Russia). Extensive clinical data and results from several clinical trials as presented in ELN guidelines on chronic myeloid leukemia (CML) therapy were summarized by Prof. Dr. Rudiger Hehlmann (Mannheim, Germany) who visited St. Petersburg this year. Dr. Elena Morozova (St. Petersburg, Russia) held a special report on therapeutic options for CML in blast crisis, especially, in cases of failed TKI treatment.

The session concerning lymphoproliferative diseases was opened by a lecture by Prof. Laurent Garderet (Paris, France) who argued for safety of autologous HSCT in multiple myeloma (MM) patients with renal insufficiency. Prof. Dr. Tapani Ruutu (Helsinki, Finland) discussed efficiency and safety of allogeneic HSCT in myeloma. Dr. Olga Pirogova (St. Petersburg, Russia) addressed different diagnostic and therapeutic aspects of MM. Modern approaches to refractory/resistant Hodgkin lymphoma therapy were reviewed by Dr. Natalia B. Mikhailova and Ilya Zyuzgin (both – St. Petersburg, Russia), whereas Dr. Elena Lepik presented multicenter results on treatment of peripheral T-cell lymphomas, a rare and heterogeneous group of lymphoproliferative disorders. The session also included reports on pathogenesis of these malignancies. E.g., Prof. Magne Borset (Trondheim, Norway) suggested possible role of certain growth and signaling factors in keeping malignant cells alive under hypoxic conditions. Dr. Katia Beider (Tel Hashomer, Israel) discussed metabolic alterations causing chemoresistance in myeloma cells caused by distinct enzymes and receptors, which could be potential therapeutic targets.

HSCT efficiency in different nonmalignant diseases was discussed in a special session. It included a comprehensive lecture by Prof. Regis Peffault de Latour (Paris, France) who discussed different therapeutic options in the patients with distinct pathogenetic variants of inborn marrow failure. Prof. Shinji Nakao (Kanazawa, Japan) presented specific genetic aspects of escape hematopoiesis in immune bone marrow failure. The lecture by Prof. Alexander D. Kulagin (St. Petersburg, Russia) concerned clinical outcomes and feasibility of repeated transplants in the patients with aplastic anemia. Prof. Dmitry Balashov (Moscow, Russia) reported on clinical results of HSCT in pediatric beta-thalassemia. Dr. Tatyana Bykova (St. Petersburg, Russia) focused on prevention and treatment of GVHD in the patients with non-malignant disorders. Dr. Alexey Polushin (St. Petersburg, Russia) reported on clinical efficiency of autologous HSCT in multiple sclerosis, highlighting the aspect of proper HSCT timing and life quality improvement in these patients.

Pediatric session was opened by Prof. Petr Sedlacek (Prague, Czech Republic) who reported the results of HSCT in pediatric ALL setting, showing great benefits from modern therapeutic protocols implemented over last 2 decades. Prof. Charlotta Niemeyer (Freiburg, Germany) described specific variants of MDS in young patients. Dr. Alesya Paina (St. Petersburg, Russia) discussed applicability and strategies of HSCT in infants with ALL and AML. Prof. Olga Aleynikova (Minsk, Republic of Belarus) presented a detailed interpretation of cytokine storm in post-transplant conditions, including CAR-T cell therapy. Dr. Natalya Myakova (Moscow, Russia) shared their experience in HSCT for treatment of pediatric non-Hodgkin lymphomas. Dr. Kirill Kirgizov (Moscow, Russia) has summarized the single-center and international data concerning late effects of HSCT in autoimmune disorders. Short communications dealt with autologous HSCT in pediatric solid tumors (Julia Dinikina, Moscow, Russia), and repeated transplants in pediatric patients (Ekaterina Pristanskova, Moscow, Russia).

Multiple complications of HSCT were covered in a special session. Dr. Zina Peric (Zagreb, Croatia) reviewed distinct role of gut microbiota in transplant-associated complications, especially, acute GVHD. Dr. Ivan S. Moiseev (St. Petersburg, Russia) has discussed clinical efficiency and opportunities for the first-line steroid-free treatment of GVHD. Dr. Egor Kulagin (St. Petersburg, Russia) reported on incidence, clinical features and outcomes of bronchiolitis obliterans following allo-HSCT. Prof. Nikolay Klimko (St. Petersburg, Russia) held a lecture on current International Guidelines for treatment of fungal invasions in hematological setting. Dr. Diana Averbuch (Jerusalem, Israel) presented novel clinically relevant aspects of Gram-negative infections in transplant clinics. Dr. Julia Rogacheva (St. Petersburg, Russia) reported about the incidence of colonization with antibiotic-resistant Gram-negative bacteria early after HSCT. Dr. Marina Popova (St. Petersburg, Russia) argued for antimicrobial stewardship program required at early terms after allogeneic HSCT.

Current activities and problems of unrelated bone marrow donor registries were discussed in a series of reports. Prof. Dietger Niederwieser (Leipzig, Germany) highlighted the ongoing recruitment of non-HLA-identical family donors, as an alternative source for allo-HSCT worldwide. Dr. Joannis Mytileneos (Ulm, Germany) focused on different features of donor/recipient compatibility when predicting HSCT outcomes. Prof. Dr. Manuel Abecasis (Lisbon, Portugal) reported about COVID-associated problems and general activities of the Portuguese Donor Registry during the pandemics. Dr. Maria Loginova (Kirov, Russia) provided recent data about development of Russian Federal Registry of HSCT donors. Dr. Alexander Alyanskiy (St. Petersburg, Russia) presented a report about joint Russian information platform for unrelated bone marrow donors.

Great attention was drawn to a special lecture given by Prof. Dr. Neal Young (Bethesda, USA) who presented a concept of evolutionary somatic mutation process underlying agerelated anemia and other diseases, also focusing on recently discovered genetic blood disorders.

Psychological and social rehabilitation issues were presented by several speakers, i.e., role of psychologist in post-HSCT rehabilitation (Svetlana Oleshko, St. Petersburg, Russia), parent-child relationships in pediatric oncology (Dr. Etienne Seigneur, Paris, France), impact of disease and therapy on body self-consciousness in children (Dr. Marie Therain, Paris, France), subjective well-being and quality of life issues (Dr. Maria Evdokimova, Moscow, Russia). Distinct rehabilitation programs are proposed for the patients with osteosarcoma (Dr. Serafima Chechelnitskaya, Moscow, Russia), and for the children with tumors of posterior cranial fossa (Dr. Vladimir Kasatkin, Moscow, Russia), as well as physical exercises after HSCT (Mohamed Jaleel, London, UK). An original standard-of-care project for functional improvement of HSCT patients (TEMPO) was presented by Anne Gonzales (Columbus, USA).

The nursing care in HSCT clinics was discussed by clinical nurses who reported on their role in managing bloodstream infections (Vladislav Kudlay, St. Petersburg, Russia), skin lesions (Elvira Gasanova, St. Petersburg, Russia), during COVID-19 pandemics in hematology setting (Olga Prokofieva, St. Petersburg, Russia, Natalia Gusleva, Moscow, Russia), centralized drug preparation (Yuliya Mirankova, Minsk, Republic of Belarus), performing bioimpedance procedure (Natalia Saltykova, St. Petersburg, Russia). A comprehensive report on the problems of nursing education in Russia was made by Dr. Natalia Petrova (St. Petersburg, Russia). A general review on nursing care in immunosuppressed patients was presented by Liz Sniderman (Memphis, USA). The role of medical nurses in pediatric rehabilitation was considered in details by Nicholette Andrews (Chicago, USA).