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CAR-T cells are an innovative treatment for an increasing number of patients, particularly since the extension of their indication to mantle lymphoma and multiple myeloma. Several complications of CAR T-cell therapy, that were first described as exceptional, have now been reported in series of patients, since its first clinical use in 2011. Among them, cardiac complications, delayed cytopenias, acute and chronic Graft versus Host Disease, and tumoral lysis syndrome are recognized as specific potent complications following CAR T-cells infusion. During the twelfth edition of practice harmonization workshops of the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), a working group focused its work on the management of these complications with focuses the epidemiology, the physiopathology and the risk factors of these 4 side effects. Our recommendations apply to commercial CAR-T cells, in order to guide strategies for the management of complications associated with this new therapeutic approach.

International audience; Texte de l'atelier Rappel du titre de l'atelier : Complications des cellules CAR T autres que les infections, CRS et ICANS: recommandations de la Société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC) Résumé en Français : Les cellules CART sont un traitement innovant, qui s'adresse à un nombre croissant de patients, en particulier depuis l'élargissement des indications au lymphome du manteau et au myélome multiple. Certaines complications, jugées rares, ont cependant été décrites de façon itérative pour des petites séries de patients, du fait de l'augmentation du nombre de patients traités dans le monde depuis les premiers essais cliniques en 2011. Parmi elles, le syndrome de lyse tumorale, les complications cardiaques, les cytopénies différées ou prolongées, la maladie du greffon contre l'hôte aiguë ou chronique, et font actuellement l'objet d'une reconnaissance en tant que complications potentielles et spécifiques du traitement par cellules CART. Nous détaillons ici l'épidémiologie, la physiopathologie connue ou suspectée, les facteurs de risque de ces complications, et proposons des recommandations pratiques de leur prévention et de leur prise en charge. Ces recommandations s'adressent aux cellules CART commerciales. Mots clés : CART cells, syndrome de lyse tumorale, complications cardio-vasculaires, cytopénies retardées, GVHD, Résumé en anglais : CAR T cells are an innovative treatment for an increasing number of patients, particularly since the extension of their indication to mantle lymphoma and multiple myeloma. Several complications of CAR T-cell therapy, that were first described as exceptional, have now been reported in series of patients, since its first clinical use in 2011. Among them, cardiac complications, delayed cytopenias, acute and chronic Graft versus Host Disease, and tumoral lysis syndrome are recognized as specific potent complications following CAR T-cells infusion. During the twelfth edition of practice harmonization workshops of the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), a working group focused its work on the management of these complications with focuses the epidemiology, the physiopathology and the risk factors of these 4 side effects. Our recommendations apply to commercial CART cells, in order to guide strategies for the management of complications associated with this new therapeutic approach.

The immune effector cell-associated syndrome (ICANS) has been described as the second most frequent specific complication following CAR-T cell therapy. The median time to the onset of neurological symptoms is five days after CAR-T infusion. ICANS can be concomitant to cytokine release syndrome but often follows the resolution of the latter. However, 10 % of patients experience delayed onset after 3 weeks of CAR-T cell infusion. The duration of symptoms is usually short, around five days if an early appropriate treatment is given. Symptoms are heterogeneous, ranging from mild symptoms quickly reversible (alterations of consciousness, deterioration in handwriting) to more serious forms with seizures or even a coma. The ICANS severity is currently based on the ASTCT score. The diagnosis of ICANS is clinical but EEG, MRI and lumbar punction can help ruling out alternative diagnoses. The first line treatment consists of high-dose corticosteroids. During the twelfth edition of practice harmonization workshops of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC), a working group focused its work on updating the SFGM-TC recommendations on the management of ICANS. In this review we discuss the management of ICANS and other neurological toxicities in patients undergoing of CAR-T cell therapy. These recommendations apply to commercial CAR-T cells, in order to guide strategies for the management neurological complications associated with this new therapeutic approach.

Infections occurring after CAR T-cells are a common complication. At the acute phase of treatment following CAR T-cell infusion, the exact incidence of infections is unknown given the overlapping symptoms with cytokine release syndrome. The risk factors for infection include the malignant underlying disease and its multiple treatments, and an immunosuppressive state induced by CAR-T cells themselves and the treatment of their complications. During the twelfth edition of practice harmonization workshops of the Francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), a working group focused its work on the management of post-CAR infectious complications. In this review we discuss anti-infection prophylaxis and vaccination of patients undergoing CAR T-cell therapy as well as a special chapter for the specific case of COVID-19. These recommendations apply to commercial CAR-T cells, in order to guide strategies for the management and prevention of infectious complications associated with this new therapeutic approach.

International audience; In Europe, two CAR T-cell products, tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), were approved in 2018. While these treatments are available for use, allogeneic hematopoietic stem cell transplantation centers still need to set up a dedicated care process inspired by established procedures in the field. In order to determine necessary resources and actors, each step of the CAR T-cell care process must be planned in advance. This process, implemented by the center's coordinating nurse, should be able to be adapted to each center's needs. The purpose of this workshop is to provide the organizational basis for such a process so that each center wishing to set up CAR-T cell activity can do so effectively. After detailing the coordinating nurse's role, we explain each step of the care process and specify essential additional tests.

In Europe, two CAR T-cell products, tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), were approved in 2018. While these treatments are available for use, allogeneic hematopoietic stem cell transplantation centers still need to set up a dedicated care process inspired by established procedures in the field. In order to determine necessary resources and actors, each step of the CAR T-cell care process must be planned in advance. This process, implemented by the center's coordinating nurse, should be able to be adapted to each center's needs. The purpose of this workshop is to provide the organizational basis for such a process so that each center wishing to set up CAR-T cell activity can do so effectively. After detailing the coordinating nurse's role, we explain each step of the care process and specify essential additional tests.

Resume Dans une demarche qui vise a uniformiser les procedures de greffe de cellules souches hematopoietiques, la Societe francophone de greffe de moelle et de therapie cellulaire (SFGM-TC) a organise les septiemes Ateliers d’harmonisation des pratiques en allogreffe en septembre 2016 a Lille. Le but de ces ateliers annuels est de trouver un terrain d’entente entre des centres qui le souhaitent dans les domaines ou la litterature ne fournit pas de reponses incontestables et consensuelles. Dans cet atelier, nous elaborons le carnet national destine aux patients autogreffes.

In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its seventh annual workshop series in September 2016 in Lille. This event brought together practitioners from across the country. Our workshop discusses the creation of a patient care logbook for patients undergoing autologous hematopoietic cell transplantation.

Resume Le nombre de greffes de cellules souches hematopoietiques (CSH) reste en constante progression sans que cette augmentation se soit accompagnee d’un ajustement des effectifs medicaux assurant le suivi des patients. Parallelement a cette insuffisance concernant les greffes, plusieurs disciplines medicales ont mis en place des delegations de tâches voire un transfert de competences. En hematologie, il existe en France peu de donnees sur la delegation de tâches, meme si quelques centres ont instaure une delegation de certaines prises en charge specifiques comme le post-greffe a des infirmieres dediees. Dans une demarche qui vise a uniformiser les procedures d’allogreffe de CSH, la Societe francaise de greffe de moelle et de therapie cellulaire (SFGM-TC) a organise les quatriemes ateliers d’harmonisation des pratiques en septembre 2013 a Lille. Dans cet atelier nous abordons la question du transfert de competence et la mise en place d’un statut infirmier de greffe pour le suivi post-greffe.