CAR-T cell therapy has established itself as one of the most promising innovations in the treatment of refractory hematologic malignancies. By modifying a patient’s own T lymphocytes to recognize and destroy tumor cells, this strategy achieves deep and long-lasting responses, even in cases where other therapies have failed. However, its implementation requires highly prepared centers with technical and organizational structures dedicated to specialized clinical management.
CAR-T Therapy: A Revolution That Requires Specialized Infrastructure
The impact of CAR-T therapy on cancer treatment is undeniable. Its clinical application, however, involves significant risks and complex logistics. Patients undergoing this type of treatment may frequently develop severe adverse effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Effective management of these complications requires hospital centers with robust infrastructure and well-trained multidisciplinary teams.
Hospital Infrastructure Required for a CAR-T Therapy Center
According to recommendations from the Brazilian Association of Hematology, Hemotherapy, and Cell Therapy (ABHH), institutions administering CAR-T therapy must have a hospital unit experienced in cellular product infusions and the use of cytotoxic medications. It is essential to have a nearby, fully equipped intensive care unit (ICU), as well as a guaranteed supply of tocilizumab, a key drug for treating CRS. The center must also have neurologists trained in managing ICANS, as well as intensivists and infectious disease specialists familiar with the complexity of the treatment.
Another fundamental aspect is immediate transfusion support, along with standardized operational protocols for all stages of the process. CAR-T centers are preferably integrated into bone marrow transplant programs due to the similarity in structural and operational requirements.
Training and Performance of the Multidisciplinary Team
Administering CAR-T therapy requires much more than a medical team. It demands an integrated team of hematologists, neurologists, intensivists, nurses, pharmacists, psychologists, nutritionists, and social workers. All must be aligned with clinical protocols and prepared to intervene quickly at any sign of complications.
Continuous training of these teams is essential, especially in a context where knowledge about CAR-T therapy side effects is still evolving. Regular meetings, case studies, and scientific updates are important tools to ensure patient safety.
Careful Patient Selection and Pre-Treatment Testing
Proper patient screening is one of the most critical steps for therapeutic success. Indication should consider the type of cancer, disease stage, and overall clinical condition. Patients with good functional status, without severe organ dysfunction or active autoimmune diseases, are ideal candidates.
Required tests include cardiac, hepatic, renal, neurological evaluations, and comprehensive viral serologies. Imaging tests, such as brain MRI, are indicated in cases of prior or suspected neurological symptoms. As this process involves cell collection, modification, and reinfusion, many of these tests need to be repeated before the start of lymphodepletion.
Lymphodepletion and Infusion of the Cellular Product
Before CAR-T cell infusion, the patient undergoes a chemotherapy regimen with fludarabine and cyclophosphamide. This step prepares the body to receive the modified cells, promoting an environment favorable to their expansion and therapeutic action. Lymphodepletion should only begin after confirming the availability of the cellular product.
Cell infusion is performed with the patient hospitalized under continuous monitoring. Although generally well tolerated, immediate reactions such as fever, chills, and, more rarely, arrhythmias or respiratory depression may occur. After infusion, patients are advised to remain close to the clinical center for at least four weeks, as many complications arise days after the procedure.
Management of the Most Common Complications: CRS and ICANS
Cytokine release syndrome (CRS) is a systemic inflammatory response caused by the massive activation of CAR-T cells. Symptoms range from mild fever to hypotension, hypoxemia, and organ failure. Treatment depends on severity and may range from antipyretics to the use of tocilizumab and corticosteroids, with intensive support in severe cases.
Immune effector cell-associated neurotoxicity syndrome (ICANS) typically occurs between the fifth and tenth day after infusion. Symptoms vary from confusion and aphasia to seizures and cerebral edema. Neurological monitoring using the ICE score, combined with corticosteroids and anticonvulsants when necessary, forms the basis of management. It is important to note that tocilizumab is not recommended in isolated ICANS cases, as it does not cross the blood-brain barrier and may worsen the condition.
Infectious Complications, Cytopenias, and Hypogammaglobulinemia
Treatment-induced immunosuppression increases the risk of opportunistic infections, especially in the first weeks. Prophylaxis with antivirals, antifungals, and antibiotics should be tailored according to the patient’s risk profile. After 30 days, the focus shifts to viral respiratory infections and reactivations such as CMV and EBV.
Severe cytopenias are common and may persist for months, requiring transfusions and the use of hematopoietic growth factors. Hypogammaglobulinemia, resulting from B-cell depletion, should be monitored through serial testing. Immunoglobulin replacement may be indicated in cases of recurrent infections associated with IgG levels below 400 mg/dL.
Structural Excellence to Ensure Safety and Outcomes
The structuring of specialized centers is essential to ensure the effectiveness and safety of CAR-T cell therapy. From patient selection to long-term follow-up, all stages require technical rigor, multidisciplinary integration, and well-defined protocols. Celluris contributes to this movement by supporting the responsible implementation of CAR-T therapy in Brazil through science, innovation, and a commitment to patient safety.
Also read on our blog about CAR-T Cell Immunotherapy in Pediatric Hematology-Oncology: Advances and Challenges.
Reference:
CLE, Diego V. et al. Consensus on genetically modified cells. I: Structuring centers for the multidisciplinary clinical administration and management of CAR-T cell therapy patients. Hematology, Transfusion and Cell Therapy, v. 43, suppl. 2, p. S3–S12, 2021. Accessed: Dec. 4, 2025.
