Short-term management of cytopenias
| . | When . | How . | Precautions . | Comments . |
|---|---|---|---|---|
| pRBC/platelet transfusions | As per institutional standards, based on patient risk profile | As per institutional standards For pRBC: consider using 1 product per time to reduce iron overload68 | Irradiation of blood products; start 7 d before leukapheresis until at least 90 d after CAR T-cell infusion | Because of the use of fludarabine |
| G-CSF | Prophylactic G-CSF: on day +2 in patients with a high-risk profile for ICAHT (eg, high CAR-HEMATOTOX score and risk profile per Table 2) | Based on individual risk profile: consider early G-CSF administration (from day +2) as prophylaxis in those at high risk for ICAHT Dosing: 5 μg/kg once daily | In patients at low risk for ICAHT, G-CSF probably not necessary | Reduced risk of febrile neutropenia (without increasing the risk of severe, or grade ≥3, CRS nor ICANS) No detrimental effect on CAR T-cell expansion kinetics or treatment outcomes73,74 |
| Therapeutic G-CSF: severe neutropenia (ANC < 500/μL) neutropenia with or without infectious complications | In case of prolonged neutropenia with/without infectious complications Dosing: 5 μg/kg once daily, consider increasing dose in case of nonresponse | Patients with intermittent neutrophil recovery often rapidly respond to G-CSF stimulation, whereas those who are aplastic are often G-CSF unresponsive | ||
| 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 is <500/μL | As per institutional standards (eg, levofloxacin or ciprofloxacin) | Warning in case of colonization by MDR pathogens | Look at local bacterial epidemiology. High local prevalence of MDR GNB might prevent the use of antibacterial prophylaxis. |
| Antiviral | All patients | Start from LD conditioning until 1 y after CAR T-cell infusion AND/OR until CD4+ count is >0.2 × 109/L Valaciclovir 500 mg twice a day or acyclovir 800 mg twice a day | ||
| Antipneumocystis | All patients | Start from LD conditioning until 1 y after CAR T-cell infusion AND/OR until CD4+ count is >0.2 × 109/L Co-trimoxazole 480 mg once daily or 960 mg 3 times each week | In case of co-trimoxazole allergy, pentamidine inhalation (300 mg once every month), dapsone 100 mg daily or atovaquone 1500 mg once daily can be considered | Can be started later depending on center guidelines |
| Systemic primary antifungal prophylaxis | Prophylaxis may be considered in case of severe neutropenia (ANC < 500/μL) and a high-risk profile for ICAHT (eg, CAR-HEMATOTOX score and risk profile per Table 2) and/or prolonged neutropenia | Mold-active prophylaxis for 1-3 mo (depending on the duration of neutropenia and use of steroids): posaconazole (300 mg/d) or micafungin (50 mg per day, IV) | In patients with prior allo-HCT, prior invasive aspergillosis, and those receiving corticosteroids (long-term >72 h, or high-dose), prophylaxis is recommended |
| . | When . | How . | Precautions . | Comments . |
|---|---|---|---|---|
| pRBC/platelet transfusions | As per institutional standards, based on patient risk profile | As per institutional standards For pRBC: consider using 1 product per time to reduce iron overload68 | Irradiation of blood products; start 7 d before leukapheresis until at least 90 d after CAR T-cell infusion | Because of the use of fludarabine |
| G-CSF | Prophylactic G-CSF: on day +2 in patients with a high-risk profile for ICAHT (eg, high CAR-HEMATOTOX score and risk profile per Table 2) | Based on individual risk profile: consider early G-CSF administration (from day +2) as prophylaxis in those at high risk for ICAHT Dosing: 5 μg/kg once daily | In patients at low risk for ICAHT, G-CSF probably not necessary | Reduced risk of febrile neutropenia (without increasing the risk of severe, or grade ≥3, CRS nor ICANS) No detrimental effect on CAR T-cell expansion kinetics or treatment outcomes73,74 |
| Therapeutic G-CSF: severe neutropenia (ANC < 500/μL) neutropenia with or without infectious complications | In case of prolonged neutropenia with/without infectious complications Dosing: 5 μg/kg once daily, consider increasing dose in case of nonresponse | Patients with intermittent neutrophil recovery often rapidly respond to G-CSF stimulation, whereas those who are aplastic are often G-CSF unresponsive | ||
| 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 is <500/μL | As per institutional standards (eg, levofloxacin or ciprofloxacin) | Warning in case of colonization by MDR pathogens | Look at local bacterial epidemiology. High local prevalence of MDR GNB might prevent the use of antibacterial prophylaxis. |
| Antiviral | All patients | Start from LD conditioning until 1 y after CAR T-cell infusion AND/OR until CD4+ count is >0.2 × 109/L Valaciclovir 500 mg twice a day or acyclovir 800 mg twice a day | ||
| Antipneumocystis | All patients | Start from LD conditioning until 1 y after CAR T-cell infusion AND/OR until CD4+ count is >0.2 × 109/L Co-trimoxazole 480 mg once daily or 960 mg 3 times each week | In case of co-trimoxazole allergy, pentamidine inhalation (300 mg once every month), dapsone 100 mg daily or atovaquone 1500 mg once daily can be considered | Can be started later depending on center guidelines |
| Systemic primary antifungal prophylaxis | Prophylaxis may be considered in case of severe neutropenia (ANC < 500/μL) and a high-risk profile for ICAHT (eg, CAR-HEMATOTOX score and risk profile per Table 2) and/or prolonged neutropenia | Mold-active prophylaxis for 1-3 mo (depending on the duration of neutropenia and use of steroids): posaconazole (300 mg/d) or micafungin (50 mg per day, IV) | In patients with prior allo-HCT, prior invasive aspergillosis, and those receiving corticosteroids (long-term >72 h, or high-dose), prophylaxis is recommended |
LD, lymphodepletion; MDR GNB, multidrug-resistant gram-negative bacteria; pRBC, packed red blood cell.