Hematology, Transfusion and Cell Therapy, Vol. 43, Supplement 2, November 2021

Editorial 1
The Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular seeks the implementation of, and access to, the CAR-T cell treatment in Brazil 1
Conflicts of interest 2
References 2
Special Articles 3
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. I: Structuring centers for the multidisciplinary clinical administration and management of CAR-T cell therapy patients 3
Introduction 4
Preparation of the center to perform the clinical use of CAR-T cells 4
Recommendations 4
Patient selection and pre-treatment evaluation 5
Recommendations 5
Conditioning or lymphodepletion 5
Recommendations 5
Infusion of CAR-T cells 5
Recommendations 6
Management of CAR-T cells complications 7
Cytokine Release Syndrome (CRS) 7
Cell-Associated Neurotoxicity Syndrome (ICANS) 7
Infections 7
Recommendations 8
Cytopenias 10
Recommendations 10
Hypogammaglobulinemia 10
Recommendations 10
Conclusion 11
Conflicts of interest 11
References 11
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. II: CAR-T cell therapy for patients with CD19+ acute lymphoblastic leukemia 13
Introduction 14
Indications 14
Patient selection, logistics and pre-infusion evaluation and management before CAR-T cells 15
Pre-apheresis 15
Apheresis 15
Post-apheresis 16
ALL management post-CAR-T cell infusion 16
Minimal residual disease 16
Consolidation with HSCT 16
Relapse 19
Conclusion 19
Conflicts of interest 19
Supplementary materials 19
References 19
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. III: anti-CD19 CAR-T cell therapy for patients with non-Hodgkin lymphoma 22
Introduction 23
DLBCL 23
MCL 25
LG-NHL 25
Patient selection 25
Bridging strategies prior to CAR-T cell treatment for B-NHL 26
CAR-T cell therapy incorporation by Brazilian public and private health systems 27
Conclusion 28
Conflicts of interest 28
References 28
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. IV: CAR-T cell therapy for multiple myeloma patients 30
Introduction 31
MM immunotherapy - novel anti-BCMA agents 31
Cellular CAR-T immunotherapy and MM 32
Idecabtagene vicleucel (Ide-Cel) 32
Ciltacabtagene autoleucel (Cilta-Cel, JNJ-4528) 32
Orvacabtagene autoleucel 32
Points of consensus 32
Conclusion 33
Conflicts of interest 33
References 33
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. V: Manufacture and quality control 35
Collection of lymphocytes 36
Concentration and enrichment of T cells 37
Activation of T cells 37
Transduction 37
Cellular expansion 37
Cryopreservation 37
Thawing and infusion 38
II- Quality control 38
Identity 38
Purity 38
Viability 39
Potency 39
Safety 40
Stability 40
Conclusions 40
Conflicts of interest 40
References 40
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. VI: Accreditation process 42
Introduction 43
Accreditation models for cell therapy products in Brazil 43
AABB/ABHH accreditation 43
General guidelines (2) 43
AABB/ABHH accreditation process 43
Chapter 1 - organization 44
Chapter 2 - resources 44
Chapter 3 - equipment management 44
Chapter 4 - agreements and contracts 44
Chapter 5 - process control (1.2) 44
Chapter 6 - documents and records (1.2) 44
Chapter 7 - product or service deviations and nonconformities and adverse events (1.2) 44
Chapter 8 - internal and external audits (2) 44
Chapter 9 - process improvement (1.2) 44
Chapter 10 - safety and facilities (1.2) 45
FACT-JACIE accreditation 45
General aspects (5) 45
FACT accreditation process (5.6) 45
Conclusion 45
Conflicts of interest 45
References 45
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. VII. Present and future of technologies for production of CAR cell therapies 46
Introduction 47
Key steps for CAR cell manufacturing 47
Viral-based CAR delivery 49
Non-viral-based CAR delivery 50
Novel approaches for CAR-T cell products 50
Modulation of CAR-T functions 50
Bispecific/Trispecific CAR-T cells 51
Automated production and CAR delivery 51
Concluding remarks 51
Conflicts of interest 51
Acknowledgments 52
References 52
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. VIII: CAR-T cells: preclinical development - Safety and efficacy evaluation 54
Introduction 55
Vectors used in CAR-T cell therapy 55
The affinity of the scFv can impact CAR specificity and off target potential 56
Characterization and control testing of vectors production 56
DNA vectors production 56
Cell banks 56
Viral vectors 56
Transducing activity 57
Characterization and control testing of CAR-T cells production 57
Serological tests 57
Cytogenetics 57
Sterility tests 57
Phenotypic and functional characterization of CAR-T cell products 58
Molecular characterization 58
Cytokine production 58
Co-culture assays 59
Number of integrated copies 59
In vivo assays - methodologies and animal models 59
Conclusion 60
Conflicts of interest 60
Acknowledgments 60
References 61
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. Special article: compassionate use and clinical trial on CAR-T cells 64
Introduction 64
Regulatory agencies 66
FDA 66
EMA 66
Anvisa 66
Conclusion 67
Conflicts of interest 67
References 67
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. Special Article: Advanced therapy medicinal products in Brazil: regulatory panorama 68
Introduction 68
Regulatory concepts 69
Regulating advanced therapies in Brazil 71
Clinical trials aspects 71
Marketing authorization aspects 73
General aspects of pharmacovigilance 75
Perspectives 75
Conflicts of interest 75
References 75
Review Article VIII
Associação Brasileira de Hematologia, Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. Review article: Cell therapy in solid tumors 78
Introduction 78
Tumor infiltrating lymphocytes (TILs) 79
CAR-T cells 80
TCR-T cells 80
Additional modalities of cell therapy 81
Conclusion 81
Conflicts of interest 82
References 82

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