{"entity":{"id":"rejuv-tx-infection-by-phase","kind":"technology","name":"Infection risk after transplant and cell therapy, phase by phase, and the prophylaxis that follows it","aka":["infection after HSCT","post-transplant prophylaxis","CMV prophylaxis","PJP prophylaxis","infection after CAR-T"],"tldr":"Which infections threaten someone after a transplant depends almost entirely on how long it has been, because the immune system returns in a known order: bacteria and fungi first, viruses such as cytomegalovirus in the middle months, encapsulated bacteria later. The preventive medicines are matched to those phases.","summary":"The phase model comes from the international guideline on preventing infectious complications after transplant and maps onto the reconstitution timeline directly.\n\nPre-engraftment, roughly day 0 to day 30. Neutropenia and damaged mucosal barriers from conditioning. The threats are bacteria, from the gut and from the central line, and invasive fungal infection, mainly Candida and Aspergillus. Prophylaxis is an antifungal, commonly fluconazole or a mould-active azole such as posaconazole or voriconazole where mould risk is higher, and in many centres an antibacterial; herpes simplex virus prophylaxis with aciclovir or valaciclovir starts here and runs on.\n\nEarly post-engraftment, roughly day 30 to day 100. Neutrophils are back but cellular immunity is not. This is the cytomegalovirus window. The randomised trial that changed it tested letermovir prophylaxis against placebo in CMV-seropositive allogeneic recipients and reduced clinically significant CMV infection; a post hoc mortality analysis of 437 patients with vital status through week 48 found an all-cause mortality hazard ratio of 0.58 (95 per cent CI 0.35 to 0.98, P = 0.04) at week 24 and 0.74 (95 per cent CI 0.49 to 1.11, P = 0.14) at week 48, and concluded that letermovir may reduce mortality by preventing or delaying clinically significant CMV infection. Where prophylaxis is not used, the alternative is pre-emptive therapy: weekly CMV PCR monitoring with treatment triggered by a rising viral load. Pneumocystis jirovecii prophylaxis, usually co-trimoxazole, starts after engraftment and continues for at least six months and for as long as immunosuppression continues. A retrospective cohort of 60 high-risk patients given letermovir found CMV reactivation in 22 per cent during prophylaxis and in a further 22 per cent after it stopped, at a median of 33 days after discontinuation, which is why monitoring continues when prophylaxis ends rather than finishing with it.\n\nLate, beyond day 100. Cellular and humoral immunity recover slowly, and in anyone with chronic graft-versus-host disease on continuing immunosuppression they may not recover for years. The characteristic late infections are with encapsulated bacteria, Streptococcus pneumoniae above all, varicella zoster virus, and late fungal and viral infection in those still immunosuppressed. Penicillin or an equivalent prophylaxis against pneumococcus is standard in people with chronic GvHD, aciclovir prophylaxis against zoster is continued for a year or more, and this is the phase in which revaccination belongs, which is the subject of the next record.\n\nAfter CAR-T the phases compress. In 133 patients treated with CD19-directed CAR-T, 30 (23 per cent) had an infection within 28 days, 6 (5 per cent) an invasive fungal infection and 5 (4 per cent) a life-threatening or fatal infection; the infection rate fell after day 28. The early risk tracks lymphodepletion, cytokine release syndrome and its treatment with tocilizumab and corticosteroids, and prolonged neutropenia; the late risk tracks B-cell aplasia and hypogammaglobulinaemia. Prophylaxis after CAR-T generally includes antiviral and Pneumocystis cover, antifungal cover in those with prolonged neutropenia, and immunoglobulin replacement where indicated.\n\nWhat a reader can do with this. Three things. Know which phase you are in, because it tells you what the tablets are for. Know that a fever in the neutropenic phase is an emergency and is treated as one within the hour, while a fever a year out is usually not, though it still needs assessing by someone who knows the history. And know that stopping prophylaxis is a decision tied to counts, immunosuppression and GvHD status rather than to a calendar date, so it is reasonable to ask what has to be true before each medicine stops.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Opportunistic_infection","links":[{"label":"Tomblyn et al., Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective (Biol Blood Marrow Transplant 2009)","url":"https://doi.org/10.1016/j.bbmt.2009.06.019"},{"label":"Marty et al., Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation (NEJM 2017)","url":"https://doi.org/10.1056/NEJMoa1706640"},{"label":"Hill et al., Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy (Blood 2018)","url":"https://doi.org/10.1182/blood-2017-07-793760"},{"label":"Cytomegalovirus events in high-risk allogeneic hematopoietic-cell transplantation patients who received letermovir prophylaxis (Transpl Infect Dis 2021)","url":"https://doi.org/10.1111/tid.13619"},{"label":"A mortality analysis of letermovir prophylaxis for cytomegalovirus in CMV-seropositive recipients of allogeneic hematopoietic cell transplantation (Clin Infect Dis 2020)","url":"https://doi.org/10.1093/cid/ciz490"},{"label":"Ogonek et al., Immune reconstitution after allogeneic hematopoietic stem cell transplantation (Front Immunol 2016)","url":"https://doi.org/10.3389/fimmu.2016.00507"}],"tags":["rejuvenation","survivorship","transplant","evidence:strong","immune","infection"],"related":["rejuv-tx-immune-reconstitution-timeline","rejuv-tx-b-cell-aplasia-and-immunoglobulin","rejuv-tx-revaccination","rejuv-tx-prolonged-cytopenias","gvhd-prophylaxis","gvhd-chronic-overview"],"cancers":[],"sections":["rejuvenation","supportive-care"],"technologies":["allogeneic-hsct","autologous-stem-cell-transplant","car-t"],"targets":[],"drugs":["tocilizumab"],"companies":[],"institutions":[],"pathways":[],"terms":["gvhd","cytopenias","crs","late-effects"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Each arm of the immune system defends against a characteristic class of organism: neutrophils against bacteria and moulds, cellular immunity against herpesviruses and intracellular pathogens, and antibody against encapsulated bacteria. Because reconstitution restores these arms in a fixed order, the infection risk moves through the same classes in the same order, and prophylaxis can be scheduled against the deficit rather than against the organism.","strengths":["The sequence is predictable, so prophylaxis is targeted rather than universal","Letermovir prophylaxis reduced clinically significant CMV infection in a randomised trial, with a mortality signal at week 24","Co-trimoxazole prevents Pneumocystis almost completely and costs very little","A published international guideline covers the whole schedule"],"limitations":["Prophylaxis brings drug toxicity, interactions and resistance pressure","CMV reactivation occurs after letermovir is stopped, at a median of 33 days in one high-risk cohort, so monitoring must continue","Duration of prophylaxis is guided by counts and immunosuppression rather than by trial evidence for a stopping rule","People with chronic GvHD may need prophylaxis for years, which is a burden in itself"]},"route":"/technologies/rejuv-tx-infection-by-phase/","neighbours":{"technology":[{"id":"rejuv-tx-what-to-ask-for","kind":"technology","name":"After a transplant or cell therapy: what to ask for","route":"/technologies/rejuv-tx-what-to-ask-for/"},{"id":"allogeneic-hsct","kind":"technology","name":"Allogeneic stem cell transplantation","route":"/technologies/allogeneic-hsct/"},{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"rejuv-tx-b-cell-aplasia-and-immunoglobulin","kind":"technology","name":"B-cell aplasia and low antibodies after CAR-T and bispecifics, and immunoglobulin replacement","route":"/technologies/rejuv-tx-b-cell-aplasia-and-immunoglobulin/"},{"id":"rejuv-tx-prolonged-cytopenias","kind":"technology","name":"Blood counts that do not come back after CAR-T: ICAHT","route":"/technologies/rejuv-tx-prolonged-cytopenias/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"gvhd-chronic-overview","kind":"technology","name":"Chronic graft-versus-host disease","route":"/technologies/gvhd-chronic-overview/"},{"id":"gvhd-prophylaxis","kind":"technology","name":"Preventing graft-versus-host disease, and what prevention costs","route":"/technologies/gvhd-prophylaxis/"},{"id":"rejuv-tx-immune-reconstitution-timeline","kind":"technology","name":"Rebuilding an immune system: the timeline, lineage by lineage","route":"/technologies/rejuv-tx-immune-reconstitution-timeline/"},{"id":"rejuv-tx-revaccination","kind":"technology","name":"Revaccination after transplant: the schedules, and where the UK and the US differ","route":"/technologies/rejuv-tx-revaccination/"}],"section":[{"id":"rejuvenation","kind":"section","name":"Recovery & Rejuvenation","route":"/fronts/rejuvenation/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"drug":[{"id":"tocilizumab","kind":"drug","name":"Tocilizumab","route":"/drugs/tocilizumab/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"cytopenias","kind":"term","name":"Cytopenias and myelosuppression","route":"/terms/cytopenias/"},{"id":"gvhd","kind":"term","name":"Graft-versus-host disease (GVHD) and graft-versus-leukaemia","route":"/terms/gvhd/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"}],"bottleneck":[{"id":"rejuv-agenda-thymus-does-not-regrow","kind":"bottleneck","name":"Nothing in routine use rebuilds an adult's thymus","route":"/bottlenecks/rejuv-agenda-thymus-does-not-regrow/"},{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}]}}