Non-Pharmacological Interventions for Neurotoxicity in Hematologic Patients Receiving CAR-T Therapy

Patients will undergo a standardised neurological evaluation. The American Society for Transplantation and Cellular Therapy (ASCT) classifies immune effector cell-associated encephalopathy (ICE), which grades the associated neurotoxicity from 1 to 4. It consists of five domains: ICE score, decreased level of consciousness, convulsions, motor findings and elevated intracranial pressure or cerebral oedema. The ICE score evaluates five cognitive domains (orientation, object naming, following instructions, writing and attention) with a maximum score of 10 points.

Functional capacity will be assessed using the Lawton and Brody Instrumental Activities of Daily Living (IADL) scale . This instrument evaluates the patient's ability to perform eight instrumental activities essential for independent living (e.g., using the telephone, shopping, preparing meals, housekeeping, laundry, transportation, medication management, and financial management). Each item is scored as 0 (dependent) or 1 (independent), yielding a total score ranging from 0 (total dependence) to 8 (complete independence). Higher scores indicate greater independence and better functional status.

Physical activity will be quantified using the International Physical Activity Questionnaire (IPAQ). The instrument comprises seven items and provides information on the time spent walking, performing moderate-intensity activities, vigorous-intensity activities, and sedentary behaviour during the last seven days. The results are expressed in metabolic equivalent task minutes per week (MET-min/week) and categorised into three levels of physical activity:

• Low: no or insufficient activity.
• Moderate: ≥3 days of vigorous activity (20 minutes/day), ≥5 days of moderate activity or walking (30 minutes/day), or a combination reaching ≥600 MET-min/week.
• High: vigorous activity on ≥3 days achieving ≥1,500 MET-min/week, or 7 days of any combination reaching ≥3,000 MET-min/week.

This classification allows the identification of patients at risk of inactivity and facilitates monitoring of changes across the intervention.

Nutritional status will be evaluated using the Patient-Generated Subjective Global Assessment (PG-SGA), a tool that has been validated for the purpose of nutritional screening in oncohematology. The PG-SGA combines patient-reported data and clinician assessment, including weight changes, dietary intake, nutrition impact symptoms, functional capacity, and physical examination findings. Patients are categorised into three groups: well-nourished, moderately malnourished/at risk of malnutrition, or severely malnourished. The instrument facilitates the identification of patients requiring nutritional interventions, thereby providing a comprehensive overview of nutritional risk within the study population.

Quality of life will be assessed using the Short Form 12 (SF-12) health survey. The SF-12 evaluates eight health domains, which are aggregated into two summary scores: the Physical Component Summary (PCS) and the Mental Component Summary (MCS). Each domain is scored according to the SF-12 scoring algorithm, resulting in standardized scores ranging from 0 to 100, with higher scores indicating better health-related quality of life.

The researcher collected attendance records, food records and self-reported activity levels as part of the follow-up of the subjects.

Duration of the initial hospitalisation following CAR-T infusion will be documented from the day of admission until discharge (days).

Hospital readmissions related to the intervention will be documented, including cause and date of readmission (number of readmissions per participant).