Table 7.

Recommendations on supportive care, and management of short/medium term complications and long-term follow-up (adapted from EBMT/EHA recommendations: Hayden et al., 2022,³⁹ Rejeski/Subklewe et al., 2023).⁴⁰

	EBMT/EHA recommendationsa39,40	Specific recommendations in ADs
pRBC/platelet transfusions in CART	As per institutional standards, based on patient risk profile For pRBC: consider using 1 product per time to reduce iron overload Irradiation of blood products; Start 7 days prior to leukapheresis until at least 90 days post CAR-T	As for hematological patients; monitoring of blood counts is mandatory in ADs (e.g. at every visit and as clinically indicated, including long-term follow up to evaluate risk of ICAHT).39,40
G-CSF in CART	Prophylactic G-CSF: On day +2 in patients with a high–risk profile for ICAHT (e.g. high CAR-HEMATOTOX score82 and risk profile) In patients at low risk for ICAHT,40 G-CSF not necessary Reduced risk of febrile neutropenia (without increasing the risk of severe, or grade ≥3, CRS nor ICANS). No detrimental effect on CART expansion kinetics or treatment outcomes	The CAR-HEMATOTOX score82 is not validated in ADs. With only few patients reported so far, no prolonged hematotoxicity has occurred in AD. Administration of G-CSF may induce disease flare in ADs. Prophylactic use of G-CSF is not recommended.
	Therapeutic G-CSF: Severe neutropenia (ANC <500/mcl) neutropenia with or without infectious complications Patients with intermittent neutrophil recovery often rapidly respond to G-CSF stimulation, while aplastic patients are often G-CSF unresponsive	HLH can be causally related to underlying ADs and should be considered as differential diagnosis in case of prolonged cytopenia. In case of prolonged grade 3–4 neutropenia, the use of G-CSF should be considered according to the risk/benefit evaluation and EBMT guidelines.39,40 Use of G-CSF may potentially favour an AD flare.
Antibacterial prophylaxis	In patients with a low risk for ICAHT, not recommended. In patients with a high–risk profile for ICAHT, prophylaxis may be considered once ANC <500/mcl. As per institutional standards (e.g. levofloxacin or ciprofloxacin). Look at local bacterial epidemiology. Warning in case of colonization by MDR pathogens.	As hematological patients Pre-exisiting humoral immune responses appear to be only marginal impacted by CD19 CART in SLE patients, but probably reduced more dramatically following BCMA CART.83 The risk of infection depends on the AD and degree of immunosuppression, and management should be carefully discussed upfront by a multidisciplinary team meeting (disease specialist, infection-disease specialist, hematologists and CART experts). A follow-up of potential infectious complications should be considered mandatory. Sufficiently long anti-viral and antibacterial prophylaxis should be maintained according to patient individual risk and in line with institutional guidelines and current EBMT guidelines.40
Anti-viral	All patients Start from LD conditioning until 1-year post-CART infusion AND/OR until CD4+ count >0.2 × 109/l Valaciclovir 500 mg bid or aciclovir 800 mg bid
Anti-pneumocystis	All patients To start from LD conditioning until 1-year post-CART infusion AND/OR until CD4+ count >0.2 × 109/l Co-trimoxazole 480 mg once daily or 960 mg three times each week In case of co-trimoxazole allergy, pentamidine inhalation (300 mg once every month) are recommended, dapsone 100 mg daily or atovaquone 1500 mg once daily can be considered
Systemic primary anti-fungal prophylaxis	Anti-fungal prophylaxis should be considered in severe neutropenia (ANC <500/mcl) with a high–risk profile for ICAHT (e.g. CAR HEMATOTOX score82 and risk profile) and/or prolonged neutropenia Mold-active prophylaxis for 1–3 months (depending on the duration of neutropenia and use of steroids): posaconazole (300 mg/day) or micafungin (50 mg i.v./day) In patients with prior allogeneic HCT, prior invasive aspergillosis and those receiving corticosteroids after CAR- T cells (long-term >72 h, or high dose), prophylaxis is recommended	As for hematological patients. The risk of infection may depend on the AD and degree and duration of immunosuppression before CTs. Management should be carefully discussed upfront by a multidisciplinary team meeting (disease specialist, infection-disease specialist, hematologists and CART experts). A follow-up of potential infectious complications should be considered mandatory.
Vaccine strategy in CART	Influenza vaccine Pre-CART: preferably vaccinate 2 weeks before LD. In B-cell aplasia low likelihood of serological response. Post-CART: >3 months after CART patients should be vaccinated irrespective of immunological reconstitution. Comments: where there is incomplete immune reconstitution or ongoing immunosuppression, there is a high likelihood of lower vaccine responses. Consensus view is that vaccination may still be beneficial to reduce rates of infection and improve clinical course. Consider boost upon B-cell recovery. SARS-CoV-2 Pre-CART: Preferably vaccinate before CART; in B-cell aplasia low likelihood of serological response. Post-CART: >3 months after CART infusion. Comments: Limited data is available on vaccine response after CART, and early reports suggest impaired serological responses in patients treated for haematological malignancies. SARS-CoV-2 vaccine-induced protection relies heavily on T-cell-mediated immunity, therefore B-cell aplasia does not seem to be a contraindication; no T-cell threshold has been defined. Postvaccination response monitoring is desirable. Guidance on re-vaccination post- CART and frequency/dosing of booster vaccines will vary between countries. National guidelines should be followed in this area of rapidly evolving clinical practice. Killed/inactivated vaccines: Post-CART: >6 months after CART and >2 months after immunoglobulin replacement. Comments: Contraindications include concurrent immunosuppressive or cytotoxic therapy. Live and non-live adjuvant vaccines Post-CART: 1 year after CAR-T and fully immune reconstituted, defined as absolute CD4 T cells >0.2 × 109/l, CD19 or CD20 positive B cells >0.2 × 109/l, no concomitant immunosuppressive or cytotoxic therapy. Comments: contraindications include, <8 months after completion of immunoglobulin replacement.	Vaccinations status should be assessed and updated before LD. Vaccination is a balance between reducing the risk of infection but comes with a theoretical risk of triggering immune events, which is a concern in the setting of ADs. Measurements of specific antibody titers may be helpful in deciding whether to vaccinate or not.9 Recently, ADWP has also provided specific COVID-19 vaccine recommendations in patients with ADs.41 Vaccination after CART therapy is effective and risk consideration should guide the decision to vaccinate before the procedure.84 In AD patients, as per hematological patients, re-vaccinations can be started from >3 months after CART therapy in fully immune reconstituted, defined as absolute CD4 T cells >0.2 × 109/l, CD19 or CD20 positive B cells >0.2 × 109/l, no concomitant immunosuppressive or cytotoxic therapy in line with EBMT guidelines.39,40 Vaccinations before full immune reconstitution can be effective and must be based on an individualized risk-assessment. Live vaccines are contraindicated in AD patients.
CRS, ICANS and ICAHT in CART	To be monitored and managed according to EBMT/EHA guidelines.39,40	As hematological patients. The early and prompt treatment of these complications is highly recommended in AD setting. Anticonvulsive prophylaxis according to institutional guidelines; mandatory in case of CNS involvement. Higher-grade toxicities were not observed in the patients with ADs already treated with CART. MDT clinical monitoring of AD patients after CART is strongly recommended.
WBC, biochemistry panel, AST, ALT, bilirubin, LDH, fibrinogen, CRP	Standard follow-up At every visit and as clinically indicated	As hematological patients.
CMV, EBV, adenovirus, COVID-19	Viral reactivation/infection (post-allogeneic HCT) As clinically indicated	As hematological patients; quarterly evaluation at least during the first year after CT, in consideration of past immunosuppression. MDT evaluation recommended.
Quantitative immunoglobulins	Consider i.v. (or s.c.) immunoglobulin replacement Consider in adults with serious/recurrent infections with encapsulated organisms and hypogammaglobulinemia (<4 g/l)	As hematological patients; consider to replace immunoglobulins in case of hypogammaglobulinemia (<4 g/l) in AD patients, due to the risk of recurrent infections. Quarterly MDT evaluation is recommended.
Endocrine function and other standard late effects testing appropriate to age	Standard follow-up Yearly or as clinically indicated	As hematological patients. The occurrence of secondary ADs85 should be investigated.

Abbreviations: AD autoimmune diseases; ALT alanine aminotransferase; ANC absolute neutrophil count; AST aspartate aminotransferase; CART chimeric antigen receptors T cells; CMV cytomegalovirus; CNS central nervous system; COVID-19 Coronavirus disease 2019; CRP C-reactive protein; CRS cytokine release syndrome; CT cellular therapy; EBMT European Society for Blood and Marrow Transplantation; EBV Epstein–Barr virus; EHA European Hematology Association; FBC full blood counts; G-CSF granulocyte colony-stimulating factor; HLH hemophagocytic lymphohistiocytosis; HCT hematopoietic stem cell transplantation; ICAHT immune effector cell-associated hematotoxicity; ICANS immune effector cell-associated neurotoxicity syndrome; LD lymphodepleting conditioning; LDH lactate dehydrogenase; MDR multidrug resistant; MDT multidisciplinary team; pRBC packed red blood cell; SARS-CoV-2 severe acute respiratory syndrome coronavirus 2; SLE systemic lupus erythematosus; WBC white blood cells.

^aThese EBMT recommendations were made for CART in hematologic malignancies and may differ to ADs.