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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