{"entity":{"id":"car-t-infection-prevention","kind":"protocol","name":"Infection screening, prophylaxis and immunoglobulin replacement around CAR T-cell therapy","aka":["CAR-T antimicrobial prophylaxis","CAR T infection prevention","IVIG after CAR T","hypogammaglobulinaemia after CAR T","PJP prophylaxis CAR T"],"tldr":"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.","summary":"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.\n\nImmunoglobulin: 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.","asOf":"2026-11-11","links":[],"tags":["protocol","cell-therapy","car-t","infection"],"related":["crs-grading-and-management","icans-grading-and-management","bispecific-step-up-dosing"],"cancers":[],"sections":[],"technologies":["car-t"],"targets":[],"drugs":["human-normal-immunoglobulin","axicabtagene-ciloleucel","tisagenlecleucel","lisocabtagene-maraleucel","brexucabtagene-autoleucel","idecabtagene-vicleucel","ciltacabtagene-autoleucel","obecabtagene-autoleucel"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-tx-immunoglobulin-replacement","hbv-hcv"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"simple":"After CAR T-cell therapy your immune system is weak for months. You will take tablets to prevent some infections and have regular blood tests. Ring the team at once if you get a fever.","domain":"cell-therapy-toxicity","setting":{"who":["doctor","nurse","pharmacist","patient-or-carer"],"where":["ward","outpatient-clinic","home"]},"population":"Adults, adolescents and children receiving CD19- or BCMA-directed CAR T cells for haematological cancers. Doses and durations differ in children (ASTCT). People receiving bispecific antibodies have separate consensus advice (see the step-up dosing protocol).","trigger":"Planning CAR T-cell therapy, and the months after infusion.","steps":[{"action":"Before lymphodepletion, screen for HIV, hepatitis B (HBsAg, anti-HBc, anti-HBs), hepatitis C and CMV, with HBV DNA if HBsAg is positive","why":"Hidden infections can flare when the immune system is suppressed; knowing about them allows prevention.","source":"astct-inf-2024","quote":"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)."},{"action":"Prevent herpes simplex and shingles with acyclovir or valacyclovir from lymphodepletion until at least 6 months after infusion","why":"Without prophylaxis, up to half of patients developed herpes virus infections, mostly shingles, in one series.","source":"astct-inf-2024","quote":"Antiviral HSV and VZV should be prevented with acyclovir or valacyclovir from the start of lymphodepletion therapy until at least 6 mo postinfusion."},{"action":"Give trimethoprim-sulfamethoxazole against Pneumocystis from count recovery until at least 6 months after infusion","why":"Pneumocystis pneumonia after CAR T cells can be severe; stopping prophylaxis at 3 months was followed by cases needing ventilation.","source":"astct-inf-2024","quote":"Prophylaxis against Pneumocystis jirovecii (PJP) with trimethoprim-sulfamethoxazole (TMP/SMX) is recommended to start post-CAR T cell infusion until at least 6 mo."},{"action":"Give antiviral prophylaxis to people with a history of hepatitis B","why":"Hepatitis B can reactivate with severe liver damage; ASTCT names entecavir until at least 12 months, EBMT/JACIE tenofovir.","source":"ebmt-2019","quote":"For patients with a history of hepatitis B infection, prophylaxis with tenofovir is recommended."},{"action":"Where antifungal prophylaxis is used, give fluconazole through neutropenia, and consider a mould-active azole for those at higher risk","why":"Fungal infections are uncommon overall but more likely with prolonged neutropenia, severe CRS or high-dose steroids.","source":"astct-inf-2024","quote":"For centers that practice universal antifungal prophylaxis, fluconazole can begin with lymphodepletion to cover the neutropenic period until neutrophil recovery."},{"action":"Decide locally between fluoroquinolone prophylaxis during neutropenia and close monitoring with prompt intravenous antibiotics","why":"Routine antibacterial prophylaxis is controversial, and none of the paediatric studies used it.","source":"astct-inf-2024","quote":"Routine prophylaxis with fluoroquinolones (alternatively 3rd generation oral cephalosporins) remains controversial"},{"action":"Investigate every fever after infusion for infection and start broad-spectrum antibiotics promptly","why":"CRS treatment with tocilizumab or steroids can hide the signs of infection.","source":"astct-inf-2024","quote":"Fevers after CAR T-cell infusion should warrant prompt infectious workup and initiation of broad-spectrum antibiotics."},{"action":"Measure IgG before CAR T cells and during the first 3 months, and keep checking B cells and immunoglobulins afterwards","why":"CD19 and BCMA CAR T cells remove antibody-making cells, which can leave people unable to fight bacterial infections for months or years.","source":"sitc-iec-2020","quote":"Following CAR T cell therapy, B cell counts and serum immunoglobulins should be measured monthly","grade":"LE: 4"},{"action":"Consider immunoglobulin replacement when IgG is 400 mg/dL or less with severe or recurrent bacterial infections, or below 200 mg/dL","why":"Replacement prevents infections in people who cannot make their own antibodies; there are no randomised trials after CAR T cells.","source":"astct-inf-2024","quote":"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"},{"action":"In children with B-cell aplasia, give immunoglobulin replacement to keep IgG at or above the institutional threshold","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.","source":"ebmt-2019","quote":"Children with B-cell aplasia should receive immunoglobulin replacement to maintain IgG levels according to institutional guidelines for IgG substitution (i.e. ≥500mg/dL)."}],"bestInClass":{"statement":"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.","sources":["astct-inf-2024","sitc-iec-2020","ebmt-2019"]},"variants":[{"name":"Tenofovir for hepatitis B (EBMT/JACIE 2019)","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.","sources":["ebmt-2019","astct-inf-2024"]},{"name":"Immunoglobulin for high-risk adults and for children under 400 mg/dL (SITC 2020)","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.","sources":["sitc-iec-2020"]},{"name":"Shorter antiviral prophylaxis in children (ASTCT 2024)","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.","sources":["astct-inf-2024"]}],"grades":[{"claim":"B-cell counts and immunoglobulins measured monthly after CAR T cells","grade":"LE: 4","source":"sitc-iec-2020"},{"claim":"Immunoglobulin for high-risk adults and children with IgG under 400 mg/dL","grade":"LE: 4","source":"sitc-iec-2020","quote":"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"},{"claim":"Antiviral and Pneumocystis prophylaxis for at least 6 months","grade":"best practice consideration (expert panel; not graded)","source":"astct-inf-2024"}],"sources":[{"key":"astct-inf-2024","label":"Best Practice Considerations by The American Society of Transplant and Cellular Therapy: Infection Prevention and Management After Chimeric Antigen Receptor T Cell Therapy for Hematological Malignancies","publisher":"ASTCT Infectious Diseases Special Interest Group, Transplantation and Cellular Therapy","year":2024,"url":"https://europepmc.org/article/PMC/PMC12826105","doi":"10.1016/j.jtct.2024.07.018","gradingScheme":"Expert panel best practice considerations synthesising mostly retrospective evidence; not graded.","read":"full-text","accessed":"2026-11-11"},{"key":"sitc-iec-2020","label":"Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events","publisher":"SITC, Journal for ImmunoTherapy of Cancer","year":2020,"url":"https://europepmc.org/article/PMC/PMC7745688","doi":"10.1136/jitc-2020-001511","gradingScheme":"Oxford Centre for Evidence-Based Medicine Levels of Evidence 2 (2016), printed after a recommendation as LE: 1 (systematic review) to LE: 5 (mechanism-based reasoning); recommendations without an LE are expert consensus.","read":"full-text","accessed":"2026-11-11"},{"key":"ebmt-2019","label":"Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE)","publisher":"EBMT and JACIE, Haematologica","year":2020,"url":"https://europepmc.org/article/PMC/PMC7012497","doi":"10.3324/haematol.2019.229781","gradingScheme":"Expert best practice recommendations; not graded.","read":"full-text","accessed":"2026-11-11"}],"upgrades":[],"gaps":["A 2026 Australian consensus statement on preventing infections after CD19 CAR T cells for lymphoma (Internal Medicine Journal) and the 2021 French (SFGM-TC) recommendations are listed in Europe PMC without open full text and were not read.","Vaccination after CAR T cells is discussed by ASTCT at length but was not set out as steps here; EBMT/JACIE 2019 made no specific recommendation.","There are no randomised trials of immunoglobulin replacement or of any antimicrobial prophylaxis after CAR T cells (ASTCT)."]},"route":"/protocols/car-t-infection-prevention/","neighbours":{"protocol":[{"id":"crs-grading-and-management","kind":"protocol","name":"Cytokine release syndrome after CAR T-cell therapy: ASTCT grading, tocilizumab and steroids","route":"/protocols/crs-grading-and-management/"},{"id":"icans-grading-and-management","kind":"protocol","name":"ICANS after CAR T-cell therapy: ICE score, ASTCT grading, steroids and seizure management","route":"/protocols/icans-grading-and-management/"},{"id":"iec-hs-management","kind":"protocol","name":"IEC-HS after CAR T-cell therapy: recognition and stepwise treatment","route":"/protocols/iec-hs-management/"},{"id":"car-t-lymphodepletion","kind":"protocol","name":"Lymphodepleting chemotherapy before CAR T-cell infusion","route":"/protocols/car-t-lymphodepletion/"},{"id":"icaht-prolonged-cytopenia","kind":"protocol","name":"Prolonged low blood counts after CAR T-cell therapy (ICAHT): grading, work-up and treatment","route":"/protocols/icaht-prolonged-cytopenia/"},{"id":"car-t-referral-and-eligibility","kind":"protocol","name":"Referral and eligibility assessment for CAR T-cell therapy","route":"/protocols/car-t-referral-and-eligibility/"},{"id":"bispecific-step-up-dosing","kind":"protocol","name":"T-cell engaging bispecific antibodies: step-up dosing, monitoring and outpatient delivery","route":"/protocols/bispecific-step-up-dosing/"}],"technology":[{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"}],"drug":[{"id":"axicabtagene-ciloleucel","kind":"drug","name":"Axicabtagene ciloleucel","route":"/drugs/axicabtagene-ciloleucel/"},{"id":"brexucabtagene-autoleucel","kind":"drug","name":"Brexucabtagene autoleucel","route":"/drugs/brexucabtagene-autoleucel/"},{"id":"ciltacabtagene-autoleucel","kind":"drug","name":"Ciltacabtagene autoleucel","route":"/drugs/ciltacabtagene-autoleucel/"},{"id":"human-normal-immunoglobulin","kind":"drug","name":"Human normal immunoglobulin (IVIg)","route":"/drugs/human-normal-immunoglobulin/"},{"id":"idecabtagene-vicleucel","kind":"drug","name":"Idecabtagene vicleucel","route":"/drugs/idecabtagene-vicleucel/"},{"id":"lisocabtagene-maraleucel","kind":"drug","name":"Lisocabtagene maraleucel","route":"/drugs/lisocabtagene-maraleucel/"},{"id":"obecabtagene-autoleucel","kind":"drug","name":"Obecabtagene autoleucel","route":"/drugs/obecabtagene-autoleucel/"},{"id":"tisagenlecleucel","kind":"drug","name":"Tisagenlecleucel","route":"/drugs/tisagenlecleucel/"}],"term":[{"id":"hbv-hcv","kind":"term","name":"Hepatitis B and C as cancer causes","route":"/terms/hbv-hcv/"},{"id":"lymphoma-tx-immunoglobulin-replacement","kind":"term","name":"Immunoglobulin replacement after CAR-T, bispecifics and long anti-CD20 treatment","route":"/terms/lymphoma-tx-immunoglobulin-replacement/"}]}}