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Infections are the commonest serious problem in the months after CAR T-cell therapy. You are first tested for hepatitis B, HIV and other viruses. Afterwards most centres give tablets against shingles, cold sores and a type of pneumonia for at least six months, check antibody levels, and may give antibody infusions if they are low and infections recur. Any fever needs a call to the team at once.
ASTCT 2024: screen before lymphodepletion with HIV antibody, hepatitis B (HBsAg, anti-HBc, anti-HBs), hepatitis C antibody, CMV IgG and HTLV-1, syphilis by risk, and baseline HBV DNA if HBsAg is positive; delay for symptomatic lower respiratory infection. Prophylaxis: acyclovir or valacyclovir from lymphodepletion until at least 6 months after infusion (shorter in children); trimethoprim-sulfamethoxazole for Pneumocystis from count recovery (by day 30) until at least 6 months, after a study in which 2 of 40 patients developed severe PJP when prophylaxis stopped at 3 months; entecavir for at-risk hepatitis B until at least 12 months; fluconazole through neutropenia where antifungal prophylaxis is universal, and mould-active azoles for higher risk; fluoroquinolone prophylaxis is controversial and may be replaced by monitoring with prompt antibiotics. Any fever after infusion needs an infection work-up and broad-spectrum antibiotics, since CRS treatment can mask infection.
Immunoglobulin: measure IgG before and in the first 3 months; consider IVIG for IgG of 400 mg/dL or less with severe or recurrent bacterial infections, and when IgG is under 200 mg/dL (ASTCT). SITC 2020 measures B cells and immunoglobulins monthly and considers replacement for high-risk adults and for children with IgG under 400 mg/dL; EBMT/JACIE 2019 keeps IgG at 500 mg/dL or more in children with B-cell aplasia and recommends tenofovir, not entecavir, for a history of hepatitis B.
Why: Hidden infections can flare when the immune system is suppressed; knowing about them allows prevention.
“Laboratory screening should include HIV antibodies (preferably fourth-generation antigen/antibody combination), hepatitis B virus surface antibody (anti-HBs) and antigen (HBsAg), HBV core Ab (anti-HBc), hepatitis C virus antibody (anti-HCV) with reflex nucleic acid testing if positive; Treponema pallidum testing based on risk factors (screening per institutional guidelines with treponemal or nontreponemal testing).”
ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024
Why: Without prophylaxis, up to half of patients developed herpes virus infections, mostly shingles, in one series.
“Antiviral HSV and VZV should be prevented with acyclovir or valacyclovir from the start of lymphodepletion therapy until at least 6 mo postinfusion.”
ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024
Why: Pneumocystis pneumonia after CAR T cells can be severe; stopping prophylaxis at 3 months was followed by cases needing ventilation.
“Prophylaxis against Pneumocystis jirovecii (PJP) with trimethoprim-sulfamethoxazole (TMP/SMX) is recommended to start post-CAR T cell infusion until at least 6 mo.”
ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024
Why: Hepatitis B can reactivate with severe liver damage; ASTCT names entecavir until at least 12 months, EBMT/JACIE tenofovir.
“For patients with a history of hepatitis B infection, prophylaxis with tenofovir is recommended.”
Why: Fungal infections are uncommon overall but more likely with prolonged neutropenia, severe CRS or high-dose steroids.
“For centers that practice universal antifungal prophylaxis, fluconazole can begin with lymphodepletion to cover the neutropenic period until neutrophil recovery.”
ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024
Why: Routine antibacterial prophylaxis is controversial, and none of the paediatric studies used it.
“Routine prophylaxis with fluoroquinolones (alternatively 3rd generation oral cephalosporins) remains controversial”
ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024
Why: CRS treatment with tocilizumab or steroids can hide the signs of infection.
“Fevers after CAR T-cell infusion should warrant prompt infectious workup and initiation of broad-spectrum antibiotics.”
ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024
Why: CD19 and BCMA CAR T cells remove antibody-making cells, which can leave people unable to fight bacterial infections for months or years.
“Following CAR T cell therapy, B cell counts and serum immunoglobulins should be measured monthly”
Why: Replacement prevents infections in people who cannot make their own antibodies; there are no randomised trials after CAR T cells.
“IVIG can also be considered when IgG < 200 mg/dL, particularly when associated with extremely low IgA levels, irrespective of the time from CAR T-cell infusion and the incidence and severity of infections”
ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024
Why: Replacement after CAR T cells has been standard in paediatric centres; EBMT notes there is no consensus on routine replacement in adults, who can keep long-lived plasma cells that go on making antibody.
“Children with B-cell aplasia should receive immunoglobulin replacement to maintain IgG levels according to institutional guidelines for IgG substitution (i.e. ≥500mg/dL).”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
ASTCT 2024, the most recent and most specific source read, sets antiviral prophylaxis for herpes viruses and Pneumocystis prophylaxis each for at least 6 months, hepatitis B prophylaxis for at least 12 months where needed, risk-adapted antifungal prophylaxis, and leaves routine antibacterial prophylaxis to local choice. On immunoglobulin replacement the sources differ in threshold: ASTCT considers IVIG at IgG of 400 mg/dL or less with severe or recurrent bacterial infection or below 200 mg/dL in anyone, SITC 2020 for high-risk adults and children under 400 mg/dL (LE: 4), and EBMT/JACIE 2019 keeps children at 500 mg/dL or more. On hepatitis B, ASTCT names entecavir and EBMT/JACIE tenofovir. ASTCT says the evidence is mostly retrospective and extrapolated from transplantation.
ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024 · SITC, Journal for ImmunoTherapy of Cancer 2020 · EBMT and JACIE, Haematologica 2020
Where it differs: Recommends tenofovir prophylaxis for a history of hepatitis B, where ASTCT 2024 names entecavir 0.5 mg daily from lymphodepletion until at least 12 months.
Evidence: Expert recommendations in both; no comparison.
EBMT and JACIE, Haematologica 2020 · ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024
Where it differs: Considers immunoglobulin supplementation for adults judged at high risk or with recurrent infections and for children with IgG under 400 mg/dL; home subcutaneous immunoglobulin for long-term B-cell aplasia.
Evidence: LE: 4.
Where it differs: Reports that children usually receive shorter antiviral prophylaxis, often 3 months (range 1 to 6 in studies), and that antibacterial prophylaxis is not universally recommended in children, adolescents and young adults.
Evidence: Expert panel best practice considerations.
ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024
| Recommendation | Grade, as printed | Source |
|---|---|---|
| B-cell counts and immunoglobulins measured monthly after CAR T cells | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2020 |
| Immunoglobulin for high-risk adults and children with IgG under 400 mg/dL “For adult patients deemed to be at high risk of infections or with recurrent infections and for children with serum IgG levels less than 400 mg/dL, immunoglobulin supplementation should be considered” | LE: 4 | SITC, Journal for ImmunoTherapy of Cancer 2020 |
| Antiviral and Pneumocystis prophylaxis for at least 6 months | best practice consideration (expert panel; not graded) | ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy 2024 |
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