- Confirmation of the presence of the CD19 antigen on the lymphoblasts - attention to the prior use of blinatumomab.
- Minimum necessary serology: hepatitis B and C and HIV.
- Patients with active infection are not eligible to receive CD19 CAR-T therapy.
- Absence of active bacterial, fungal or viral infection.
- Minimal lymphocyte count:
- total lymphocytes > 500/mm3 and CD3 > 150/mm3.
- A low number of blood CD3 usually make various apheresis procedures necessary.
- In patients who underwent allogeneic transplant, a minimum 12-week interval should be respected between the transplant and the apheresis. It is important not to have active acute or chronic host versus graft disease at the moment of apheresis and already suspended immunosuppressants, two weeks of calcineurin inhibitors cyclosporine/tacrolimus and one week of corticoid.
- The minimum washout period is variable and is recommended prior to the apheresis for the following therapies:
- 1-day intrathecal cytarabine
- 3-day short action anti proliferative (ex. hydroxyurea)
- 5-day short action growth factors (ex. G-CSF) and nilotinib
- 7-day intrathecal methotrexate and cytarabine in doses < 100 mg/m2
- 14-day systemic chemotherapy and, in general, long-action growth factors, imatinib, dasatinib, ponatinib and blinatumomab.
- 12-week fludarabine and bendamustine
- 4-week PEG-asparaginase and DLI
- 8-week clofarabine and cranial radiotherapy
- mínimum of 8 weeks of lytic agents, such as ATG and campath. Some manufacturers suggest a longer washout (6 months) to be discussed case by case by the manufacturer's medical team, if a smaller interval is possible
- 12-week fludarabine and bendamustine
- 6-month ATG or alemtuzumab. It is suggested to make contact with the CAR-T manufacturer to define if a shorter interval than this is possible.
- A minimally adequate function of the kidneys, liver, heart and lungs are indicated for the performance of apheresis. The patient must be previously evaluated by the apheresis team. An evaluation of the venous access is fundamental. In case of peripheral access in adults and most pediatric patients, the use of a central catheter of the dialysis type is recommended.
- It is important to verify that the patient is not pregnant and that that patient agrees to follow the effective contraception following the CAR-T cell infusion. Conception is not recommended following the CAR-T cell infusion, as the risk for the child is unknown. |
Evaluation of the ALL status (bone marrow tap and lumbar tap). The high tumor load increases the chance of CRS and ICANS
- Evaluation of the presence of active bacterial, fungal or viral infection. In case of active infection, it is important to weigh the risk and the benefit of initiating chemotherapy before complete control.
- Evaluation of the presence of new toxicities of target organs which might impact the capacity of the patient to receive chemotherapy (or subsequent CAR-T infusion).
- Evaluation of the presence of acute or chronic GVHD which might have been reactivated following the apheresis.
- Central venous access with at least a two-way port.
- Vaccines with live vírus should be avoided in the 6 weeks preceding the lymphodepletion.
- It is recommended to request from the patient or legal guardian prior to initiating lymphodepletion a consent term informing the risks of serious complications associated with the treatment.
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Evaluation of the presence of rapidly progressive disease on the days preceding the infusion, as this increases the risk for CRS and the failure of the treatment.
- Absence of active bacterial, fungal or viral infection If there is active infection, the infusion should be postponed and the patient should receive complete treatment for the infection. The presence of active infection at the moment of the CAR-T infusion increases significantly the risk for CRS.
- Absence of active GVHD - acute, grades II - IV, and extensively chronic.
- Exclusion of the presence of gestation
- Evaluation of the presence of new toxicities in target organs which may impact the patient capacity to receive the CAR-T infusion. Special attention to the necessity for oxygen supplementation prior to the infusion and the presence of uncontrolled arrhythmias.
- A minimum and variable washout period is recommended prior to the CAR-T infusion for the following therapies:
- 3-day short-action proliferative agents (ex. hydroxyurea), tyrosine-kinase inhibitors and corticosteroids at a therapeutic dose. The use of hydrocortisone replacement or an equivalent at a dose less than 12mg/m2/day is permitted. The prescription of steroids for the management of adverse reactions during and following the CAR-T infusion.
- 5-day short-action growth factors (ex. G-CSF) and nilotinib
- 7-day vincristine, 6-MP, 6-TG, methotrexate (< 25mg/m2), cytarabine (< 100mg/m2), non-pegylated asparaginase, intrathecal chemotherapy (methotrexate, cytarabine)
- 14-day Other systemic chemotherapies, such as clofarabine, methotrexate (> 25mg/m2), cytarabine (> 100mg/m2) and Other agents (except those used in the lymphodepletion) and radiotherapy for sites beyond the central nervous system.
- 4-week PEG-asparaginase or immunosuppressants used in the treatment of GVHD. This last restriction is mainly to ensure that there be no relapse of GVHD prior to the CAR-T infusion.
- 6-week infusion of lymphocytes from the donor (DLI)
- 8-week cranial radiotherapy and lytic agents for T-cells, such as ATG and alemtuzumab
- Contact with the intensive therapy team.
- Verify with the pharmacy the availability of at least two doses of tocilizumab reserved for the patient for treatment of CRS |
Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular Consensus on genetically modified cells. II: CAR-T cell therapy for patients with CD19+ acute lymphoblastic leukemia