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BACKGROUND: Hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell therapy (CAR-T) recipients are at higher risk of serious complications of COVID-19 infection than the general population. Though there is evidence that monoclonal antibodies (MCA) against COVID-19 reduce the risk of death and hospitalization in the general population, data regarding their efficacy in HSCT and CAR-T recipients remains scarce. METHODS: We conducted a retrospective review of HSCT and CAR-T recipients to compare 30-day outcomes between patients who did and did not receive MCA after their first episode of COVID-19 between May 1, 2020 and December 31, 2022. Outcomes were defined as the most severe complication experienced out of the following: 30-day emergency department visit, hospitalization, intensive care unit admission, and death after COVID-19 infection. RESULTS: We identified 166 patients comprised of 53.6% allogeneic HSCT, 35.5% autologous HSCT, and 10.8% CAR-T recipients; 107 had received a COVID-19 vaccine >2 weeks prior to testing positive, and 40 were treated with MCA. After adjusting for age, presence of symptoms at the initial positive test, and COVID-19 vaccination status, patients who did not receive MCA were five times more likely to develop complications after COVID-19 infection (adjusted odds ratio 5.0 [95% CI, 1.9-12.8], p = .001). CONCLUSION: HSCT and CAR-T recipients who received MCA following COVID-19 infection were far less likely to develop COVID-related complications than those who did not receive MCA, regardless of vaccination status. This underscores the potential benefit of developing novel MCA with efficacy against circulating COVID-19 strains.
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Anticuerpos Monoclonales , COVID-19 , Trasplante de Células Madre Hematopoyéticas , Receptores Quiméricos de Antígenos , SARS-CoV-2 , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , COVID-19/inmunología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , SARS-CoV-2/inmunología , Anticuerpos Monoclonales/uso terapéutico , Receptores Quiméricos de Antígenos/inmunología , Inmunoterapia Adoptiva/métodos , Anciano , Hospitalización/estadística & datos numéricos , Resultado del Tratamiento , Vacunas contra la COVID-19/inmunologíaRESUMEN
This study explored the efficacy of intravenous immunoglobulin (IVIG) prophylaxis in reducing infection-related hospitalizations (IRHs) in MM patients. This was a retrospective study of MM patients who received IVIG at Taussig Cancer Center between July 2009 and July 2021. The primary endpoint was rate of IRHs per patient-year on-IVIG versus off-IVIG. 108 patients were included. There was a significant difference in the primary endpoint of rate of IRHs per patient-year on-IVIG versus off-IVIG in the overall study population (0.81 vs. 1.08; Mean Difference [MD], -0.27; 95% Confidence Interval [CI], -0.57 to 0.03; p value [P] = 0.04). The subgroup of patients with a 1-year period of continuous IVIG (49, 45.3%), the subgroup with standard-risk cytogenetics (54, 50.0%) and the subgroup with 2 or more IRHs (67, 62.0%) all showed a significant reduction in IRHs while on-IVIG versus off-IVIG (0.48 vs. 0.78; MD, -0.30; 95% CI, -0.59 to 0.002; p = 0.03) and (0.65 vs. 1.01; MD, -0.36; 95% CI, -0.71 to -0.01; p = 0.02) and (1.04 vs. 1.43; MD, -0.39; 95% CI, -0.82 to 0.05; p = 0.04) respectively. IVIG showed significant benefit in reducing IRHs in the overall population and in multiple subgroups.
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Inmunoglobulinas Intravenosas , Mieloma Múltiple , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , HospitalizaciónRESUMEN
BACKGROUND: Vaccine preventable diseases can affect solid organ transplant recipients post-transplant. Therefore, the administration of vaccines and assessment of serologic response should be prioritized in the pre-transplant period. METHODS: This single-center, retrospective study included 349 adult heart or lung transplant candidates between December 1, 2017 and November 30, 2019. We describe vaccination or serologic status for hepatitis A, hepatitis B, tetanus, pneumococcal, influenza, and other recommended vaccinations among heart or lung transplant candidates. RESULTS: Eighty-two heart transplant candidates (91%) and 77 lung transplant candidates (30%) received an ID consult prior to transplant. More patients completed the pneumococcal series (66.7% vs. 28.6%, P = .045) in the heart transplant group that received an ID consult. In the lung transplant group, patients with an ID consult demonstrated higher rates of immunity to hepatitis A (84.4% vs. 72.9%, P = .047), hepatitis B (75.3% vs. 56.9%, P = .005), and measles (71.4% vs. 52.5%, P = .005) compared to those without. CONCLUSIONS: Our results demonstrate the value of consulting ID and administering vaccinations in the early evaluation phase, prior to transplant listing. Opportunities remain to better optimize vaccination rates prior to transplant in heart and lung transplant candidates.
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Vacunas contra la Influenza , Receptores de Trasplantes , Adulto , Humanos , Pulmón , Estudios Retrospectivos , VacunaciónRESUMEN
INTRODUCTION: Blood stream infections (BSI) frequently cause morbidity and mortality in allogeneic (allo) hematopoietic cell transplant (HCT) recipients. Characteristics of causative organisms shortly before death have not been previously described. Early treatment with antimicrobial agents targeting the recent surge in multidrug-resistant (MDR) pathogens may lead to better outcomes. METHODS: This is retrospective study including 529 allo HCT recipients who died between 2000 and 2013. All patients who had BSI that happened 72 hours before death were included. BSI and criteria for antimicrobial resistance were defined according to the Centers for Disease Control and Prevention and the National Healthcare Safety Network surveillance criteria. RESULTS: Overall, 104 BSI were identified from 91 patients. Bacterial infections accounted for 87% of the infections which were comprised by 37% gram-negative organisms and 50% gram-positive bacteria. The most common species were Enterococcus (30%), Staphylococcus (16%), and Pseudomonas (16%). Most enterococci were vancomycin resistant (87%), 100% of staphylococci were resistant to methicillin, and 64% of Pseudomonas were MDR. Over time there was a significant increase in vancomycin-resistant enterococcal (P = .01) and gram-negative BSI (P = .01). Blood stream infections were either the primary or secondary cause of death in 53% of patients. CONCLUSIONS: In allo HCT recipients, vancomycin-resistant enterococcal infections caused the majority of BSI 72 hours prior to death. Our findings provide information that may guide empiric antibiotic coverage in critically ill HCT recipients.
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Bacteriemia , Trasplante de Células Madre Hematopoyéticas , Enterococos Resistentes a la Vancomicina , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Retrospectivos , Receptores de TrasplantesRESUMEN
BACKGROUND: Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. CMV cell-mediated immunity (CMV-CMI) as determined by a peptide-based enzyme-linked immunospot (ELISPOT) CMV assay may identify patients at risk for clinically significant CMV infection (CS-CMVi). METHODS: The CS-CMVi was defined as CMV viremia and/or disease necessitating antiviral therapy. CMV-CMI was characterized as high when the intermediate-early 1 (IE-1) antigen spot counts (SPCs) were >100 (cutoff 1) or when the IE-1 and phosphoprotein 65 antigen SPCs were both >100 SPCs per 250 000 cells (cutoff 2), and a low CMV-CMI when SPCs were below these thresholds. In this prospective multicenter study, we evaluated CMV-CMI every 2 weeks from the pretransplant period until 6 months posttransplantation in 241 allo-HCT recipients with positive CMV serostatus. The primary endpoint was CS-CMVi occurring within 2 weeks of the last measurement of CMV-CMI. RESULTS: CS-CMVi occurred in 70 allo-HCT recipients (29%). CMV-CMI was low in patients who experienced CS-CMVi (94%), whereas those who had a high CMV-CMI were less likely to have CS-CMVi (Pâ <â .0001). Patients with CS-CMVi had higher all-cause mortality (Pâ =â .007), especially those with low CMV-CMI (Pâ =â .035). On multivariable analysis, CMV-CMI, sex, race, antithymocyte globulin, and steroid use were independent predictors of CS-CMVi, and the time from transplant to engraftment was the only predictor of mortality. CONCLUSIONS: Measurement of CMV-CMI using a novel ELISPOT assay would be useful clinically to monitor allo-HCT recipients and distinguish between those at risk of developing CS-CMVi and requiring antiviral prophylaxis or therapy and those who are protected.
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Infecciones por Citomegalovirus , Trasplante de Células Madre Hematopoyéticas , Antivirales/uso terapéutico , Citomegalovirus , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/epidemiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Inmunidad Celular , Estudios ProspectivosRESUMEN
Vaccination is an effective strategy to prevent infections in immunocompromised hematopoietic stem cell transplant recipients. Pretransplant vaccination of influenza, pneumococcus, Haemophilus influenza type b, diphtheria, tetanus, and hepatitis B, both in donors and transplant recipients, produces high antibody titers in patients compared with recipient vaccination only. Because transplant recipients are immunocompromised, live vaccines should be avoided with few exceptions. Transplant recipients should get inactive vaccinations when possible to prevent infection. This includes vaccination against influenza, pneumococcus, H. influenza type b, diphtheria, tetanus, pertussis, meningococcus, measles, mumps, rubella, polio, hepatitis A, human papillomavirus, and hepatitis B. Close contacts of transplant recipients can safely get vaccinations (inactive and few live vaccines) as per their need and schedule. Transplant recipients who wish to travel may need to get vaccinated against endemic diseases that are prevalent in such areas. There is paucity of data on the role of vaccinations for patients receiving novel immunotherapy such as bispecific antibodies and chimeric antigen receptor T cells despite data on prolonged B cell depletion and higher risk of opportunistic infections.
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Vacunas contra la Influenza , Receptores de Trasplantes , Humanos , Huésped Inmunocomprometido , Trasplante de Células Madre , VacunaciónRESUMEN
BACKGROUND: Infections are the most common cause of non-relapse mortality in adult allogeneic hematopoietic stem cell transplant (allo HSCT) recipients. Acute gastrointestinal graft-vs-host disease (GI GVHD) often leads to friable mucosa as well as treatment interventions which can increase risk of infection. Our primary objective was to describe the relationship between increasing grades of acute GI GVHD and incidence of bloodstream infections (BSI). METHODS: We reviewed 441 adults who underwent allo HSCT from 2011 to 2017 and were clinically diagnosed with GI GVHD, non-GI GVHD, or no GVHD based on the modified Glucksberg scale within the first 100 days of transplantation. The maximum grades of acute GI GVHD and non-GI GVHD were used in the analysis. BSI was defined based on the presence of a blood culture positive for bacteria or fungi and treatment with antibiotics. The incidence of BSI within the first 180 days of transplantation was estimated with the cumulative incidence method. Fine and Gray regression was used to assess association between clinical grade of acute GI GVHD and BSI risk, adjusting for grade of non-GI GVHD and for other significant baseline patient risk factors for BSI identified by multivariable analysis. Results are shown as hazard ratio (HR) and 95% confidence interval (CI). A similar analysis was conducted in 130 patients with histologic grade of acute GI GVHD. RESULTS: Overall BSI incidence by day 180 was 32%; gram-negative bacilli were the predominant organisms, followed by gram-positive cocci and fungi. Patients with grade 4 acute GI GVHD had higher risk of BSI as compared to patients with no GI GVHD (HR 2.98, CI 1.65-5.37, P < .001), while those with grade 3 acute GI GVHD had similar BSI risk (HR 0.89, CI 0.36-2.21, P = .81). Grade of GI GVHD had no association with risk of non-BSI. Results were similar in patients with histologic grade acute GI GVHD. Patients who developed BSI or non-BSI had significantly higher overall mortality risk compared to those without infectious complications (HR 2.52, CI 1.92-3.31, P < .001 for BSI; HR 1.60, CI 1.20-2.13, P = .001 for non-BSI). CONCLUSIONS: Grade 4 acute GI GVHD is associated with a higher risk of BSI, which is in turn associated with a higher risk of overall mortality in this population. Understanding the relationships between acute GI GVHD, BSI, and overall mortality can guide future treatment strategies for adult allo HSCT recipients.
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Bacteriemia/complicaciones , Enfermedad Injerto contra Huésped/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante Homólogo/efectos adversos , Enfermedad Aguda , Adolescente , Adulto , Anciano , Femenino , Enfermedad Injerto contra Huésped/microbiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The spectrum of infectious complications in autologous hematopoietic cell transplant recipients (AHCT) with multiple myeloma has not been well described in the recent era of novel agent induction and improved supportive care. METHODS: We conducted a retrospective cohort study of 413 adult myeloma AHCT recipients at our institution from 2007-2016 to describe the cumulative incidence and risk factors for various infections and FN occurring within the first 100 days after AHCT. Additionally, landmark analysis was done among 404 patients who survived at least 100 days after transplant admission to estimate the association of infections with subsequent non-relapse mortality (NRM), overall survival (OS), and relapse-free survival (RFS). RESULTS: Cumulative incidences (95% CI) of infection events by day 100 were: FN 43% (38-48), any infection 21% (17-25), bacterial 17% (14-21), viral 4% (3-7) and fungal 1% (0.5-3), central line-associated blood stream infection 3% (2-6), and Clostridium difficile colitis 6% (4-8). Patients with infection had a longer initial transplant hospitalization (median 17 vs 16 days, P < 0.01), more readmissions (31% vs 8%, P < 0.01), and spent more days in hospital in first 100 days (median 18 vs 16 days, P < 0.01). A 100-day mortality was low and similar between groups (2% vs 1%, P = 0.28). In landmark analysis of 404 100-day survivors, OS was worse among patients with early infections (hazard ratio 1.54 [1.03-2.30], P = 0.03), although there was no difference in NRM and RFS. CONCLUSIONS: Notwithstanding advances in supportive care, early infectious complications remain a relevant source of morbidity and require attention in myeloma AHCT recipients.
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Trasplante de Células Madre Hematopoyéticas/efectos adversos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/microbiología , Adulto , Factores de Edad , Anciano , Infecciones Bacterianas/complicaciones , Infecciones por Clostridium/complicaciones , Supervivencia sin Enfermedad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Micosis/complicaciones , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Factores de Riesgo , Trasplante Autólogo/efectos adversos , Virosis/complicaciones , Adulto JovenRESUMEN
BACKGROUND: Infectious diseases (ID) specialists with experience in managing infections in transplant recipients and other immunocompromised hosts are increasingly needed as these fields expand. METHODS: To evaluate experiences and identify trainee-described needs in transplant infectious diseases (TID) training, the American Society of Transplantation, Infectious Diseases Community of Practice (AST IDCOP) surveyed ID fellows across the United States and TID fellows in the United States and Canada and received responses from 203 ID fellows and 13 TID fellows. RESULTS: Among ID fellows, the amount of TID training during ID fellowship was rated between less than ideal and adequate. Reasons cited included limited frequency of didactic activities and limited exposure to transplant patients during training. In particular, ID fellows at low-volume transplantation centers expressed interest in more TID training time, away training opportunities, and specific TID didactics. Educational resources of high interest among trainees were case-based interactive websites, mobile phone applications with TID guidelines, and a centralized collection of relevant articles. Pediatric ID fellows reported lower satisfaction scores with TID training, while TID fellows were overall satisfied or more than satisfied with their training experience. CONCLUSION: Findings from this survey will inform local and national TID educational initiatives.
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Enfermedades Transmisibles/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Internado y Residencia/métodos , Trasplante de Órganos/efectos adversos , Canadá , Enfermedades Transmisibles/diagnóstico , Enfermedades Transmisibles/inmunología , Curriculum , Becas , Humanos , Internado y Residencia/estadística & datos numéricos , Aplicaciones Móviles/estadística & datos numéricos , Satisfacción Personal , Guías de Práctica Clínica como Asunto , Encuestas y Cuestionarios , Estados UnidosAsunto(s)
COVID-19 , Trasplante de Órganos , Vacunas contra la COVID-19 , Humanos , SARS-CoV-2 , Receptores de TrasplantesRESUMEN
Recombinant herpes zoster (HZ) vaccines may be an alternative to the live-attenuated HZ vaccine for immunocompromised individuals. This was a phase 1/2, randomized, observer-blind, placebo-controlled study in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous hematopoietic stem-cell transplant 50 to 70 days earlier. Subjects (N = 121) were randomized 1:1:1:1 to receive (at months 0, 1, 3) three doses of 50 µg varicella-zoster virus glycoprotein E (gE) adjuvanted with AS01B, 3 doses of gE adjuvanted with AS01E, 1 dose of saline followed by 2 doses of gE/AS01B, or 3 doses of saline. One month after the last dose (6 months after transplant), frequencies of CD4(+) T cells expressing ≥2 activation markers after induction with gE and anti-gE antibody concentrations were higher with all gE/AS01 regimens than with saline. Both responses persisted up to 1 year in subjects vaccinated with gE/AS01. Immune responses were higher in the gE/AS01B 3-dose group than in the gE/AS01B 2-dose group but not higher than in the gE/AS01E 3-dose group. One serious adverse event (pneumonia) was considered vaccine related. Both formulations and both schedules were immunogenic and well tolerated in this population. This study was registered at www.clinicaltrials.gov as #NCT00920218.
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Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Vacuna contra el Herpes Zóster/uso terapéutico , Herpesvirus Humano 3/inmunología , Adulto , Anciano , Método Doble Ciego , Femenino , Neoplasias Hematológicas/inmunología , Vacuna contra el Herpes Zóster/inmunología , Enfermedad de Hodgkin/inmunología , Enfermedad de Hodgkin/terapia , Humanos , Leucemia Mieloide Aguda/inmunología , Leucemia Mieloide Aguda/terapia , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/inmunología , Mieloma Múltiple/terapia , Trasplante Autólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Despite influenza vaccination being an integral part of prenatal care, vaccination rates remain low. To evaluate the impact of pre-visit video education on patients' vaccination health beliefs and vaccination rate. STUDY DESIGN: From November 2013-January 2014 unvaccinated patients seen for routine prenatal carewere randomized into 2 study groups: pre-visit vaccination video education or control. Pre- and post-video health beliefs were assessed on a 5-point scale, and unvaccinated participants were subsequently interviewed by phone. RESULTS: In 105 randomized participants, intervention positively influenced health beliefs, as demonstrated by differences in mean pre- versus post-video scores for intervention versus control: vaccination may harm mother (difference = -0.05, p = 0.009) and baby (difference = -0.44, p = 0.015), and vaccination can protect mother (difference = 0.49, p = 0.003) and baby (difference = 0.59, p = 0.001). Vaccination rates were 28% intervention and 25% control (p = 0.70). Provider recommendation was associated with vaccination (47% if recommended vs. 12% if not, p < 0.001). Phone interviews revealed susceptibility, to influenza and vaccine safety as primary reasons for remaining unvaccinated. CONCLUSION: Video education positively influenced vaccination health beliefs without impacting vaccination rates. Physician's recommendation was strongly associated with participant's decision to become vaccinated and may be most effective when emphasizing influenza vaccination's protective impact on the newborn,.
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Vacunas contra la Influenza , Educación del Paciente como Asunto/métodos , Atención Prenatal , Grabación de Cinta de Video , Adulto , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Gripe Humana/prevención & control , Embarazo , Complicaciones Infecciosas del Embarazo/prevención & control , Vacunación/estadística & datos numéricosRESUMEN
Viral infections continue to cause significant morbidity in immunosuppressed kidney transplant patients. Although cytomegalovirus, Epstein-Barr virus and polyoma "BK" virus are more frequently encountered, the Adenovirus can cause multi-organ system infections, and may be difficult to diagnose because it is not often considered in the initial work up in kidney transplant recipients. We present an unusual case of a kidney recipient 1 year post-transplant with disseminated adenoviral infection, who had an initial presentation of lower urinary tract voiding dysfunction with hematuria and sterile pyuria. This progressed to a severe tubulointerstitial nephritis and acute kidney injury that improved with reduction of immunosuppression. Serial blood viral loads are useful for monitoring the course of infection. Urinary adenoviral infection should be considered in the differential diagnosis whenever a kidney transplant recipient presents with unexplained lower tract voiding dysfunction, hematuria, and sterile pyuria. The allograft kidney and bladder can be targets of viral proliferation. Early diagnosis with reduction of immunosuppressive therapy is essential to clear the virus and maintain allograft function.
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Infecciones por Adenoviridae/diagnóstico , Terapia de Inmunosupresión , Trasplante de Riñón , Nefritis Intersticial/virología , Insuficiencia Renal/terapia , Infecciones Urinarias/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Febrile neutropenia (FN) is an oncologic emergency frequently encountered in hematopoietic cell transplant (HCT) and chimeric antigen receptor (CAR) T-cell therapy patients, which requires immediate initiation of broad-spectrum antibiotics. Data regarding antibiotic de-escalation (DE) in neutropenic patients are limited, and guideline recommendations vary. A clinical protocol for antibiotic DE of broad-spectrum agents was implemented if patients were afebrile after 72 hours and had no clinical evidence of infection. The primary endpoint was the difference in the number of antibiotic therapy days between the pre-and post-DE protocol implementation group. Secondary endpoints included rates of subsequent bacteremia during index hospitalization, 30-day mortality, and hospital length of stay. Retrospective chart reviews were conducted to assess outcomes for patients who received allogeneic HCT, autologous HCT, or CAR T-cell therapy under the antibiotic de-escalation protocol (post-DE) compared to those who did not (pre-DE). The pre-DE group underwent HCT/CAR T-cell from February 2018 through September 2018 (n=64), and the post-DE group from February 2019 through September 2019 (n=67). The median duration of antibiotics was significantly lower in the post-DE group (6 days; range 3-60 days) compared to the pre-DE group (8 days; range 3-31 days) (p=0.034). There were no differences in any secondary endpoints. We conclude that antibiotic DE in neutropenic HCT or CAR T-cell therapy patients treated with broad-spectrum antibiotics for at least three days who are afebrile and without documented infection appears to be a safe and effective practice. Adopting it significantly reduces the number of days of antibiotics without compromising patient outcomes.
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BACKGROUND: Reduction in immunosuppression is considered the therapy of proven benefit for BKV infection in renal transplantation, but the use of leflunomide has also been reported. It was observed at this center that the patterns of viral load response while on leflunomide appear to fall into two distinct types. METHODS: Medical records of 22 kidney and kidney-pancreas recipients at a single center who received leflunomide therapy for BKV DNAemia were reviewed. Information was collected on demographics, BKV viral loads, other antiviral therapy, immunosuppressive drug levels and doses, adverse effects, and graft and patient outcomes. RESULTS: Eighteen of 22 cleared BKV viremia, and 12 of 22 had preserved allograft function; only two graft losses occurred in the screening era among leflunomide-treated patients. Two patterns of viral load reduction were observed, termed the "smooth" and the "zigzag" pattern, which differed in mean time to clear of BKV DNA (2.9 vs. 19.5 months, p = 0.0073). Graft preservation was correlated with lower serum creatinine (SCr) at the start of leflunomide therapy. CONCLUSIONS: Long courses and "zigzag" fluctuations in viral load can occur in patients who eventually clear BKV on leflunomide with preserved allograft function. Intermittent increases in viral load do not necessarily portend therapeutic failure. Although the utility of leflunomide is still debated in the transplant community, this information may be useful to clinicians who choose to use it in selected patients.
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Virus BK/efectos de los fármacos , ADN Viral/sangre , Isoxazoles/uso terapéutico , Trasplante de Riñón , Infecciones por Polyomavirus/inmunología , Infecciones Tumorales por Virus/inmunología , Carga Viral/inmunología , Virus BK/inmunología , Femenino , Rechazo de Injerto/inmunología , Humanos , Inmunosupresores/uso terapéutico , Leflunamida , Masculino , Infecciones por Polyomavirus/tratamiento farmacológico , Infecciones por Polyomavirus/virología , Infecciones Tumorales por Virus/tratamiento farmacológico , Infecciones Tumorales por Virus/virología , Viremia/inmunologíaRESUMEN
We prospectively screened 609 consecutive kidney (538) and kidney-pancreas (71) transplant recipients for BK viremia over a 4-year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥ 10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥ 10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30-50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus-associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22-744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation.
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Terapia de Inmunosupresión/efectos adversos , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/diagnóstico , Tacrolimus/administración & dosificación , Infecciones Tumorales por Virus/diagnóstico , Adulto , Anciano , Virus BK , Biopsia , Femenino , Humanos , Riñón/patología , Riñón/virología , Enfermedades Renales/virología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/sangre , Trasplante de Páncreas/efectos adversos , Complicaciones Posoperatorias/diagnóstico , Estudios Prospectivos , Tacrolimus/efectos adversos , Tacrolimus/sangre , Carga ViralRESUMEN
BACKGROUND: Our institution has used trimethoprim-sulfamethoxazole (TMP-SMX) as the antibacterial agent of choice for infection prophylaxis during the pre-engraftment period in the allogeneic transplant (allo-HCT) population. METHODS: This retrospective, single center study was developed to compare the safety of that antibacterial prophylaxis to fluoroquinolones in allo-HCT. The primary endpoint was time to neutrophil engraftment. RESULTS: A total of 366 patients were reviewed (TMP-SMX n = 332, fluoroquinolone n = 34). No difference in days to neutrophil engraftment was found (median 15 versus 16 days, p = 0.62). Hyperkalemia was more common in the TMP-SMX cohort (32.2% versus 14.7%, p = 0.035); this did not contribute to a higher rate of agent discontinuation or arrhythmia. There was no significant difference in the incidence of neutropenic fever; however, those in the TMP-SMX cohort were more likely to have microbiologically confirmed bacteremia (24.1% versus 8.8% respectively, p = 0.043). There was no significant difference in infections. No long-term implication of prophylactic antibacterial agent selection was observed in terms of graft-versus-host-disease, underlying disease relapse, or mortality. CONCLUSION: The use of TMP-SMX was associated with a higher likelihood of bacteremia and hyperkalemia; however, this did not result in increased hospital stay, escalation of care, or mortality. The use of TMP-SMX for prophylaxis during the pre-engraftment period for allo-HCT recipients is safe and effective.
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Background: Cytomegalovirus (CMV) infection is a common opportunistic infection after allogeneic hematopoietic cell transplant (alloHCT). We explored whether a change in CMV cell-mediated immunity during the first month after transplant predicts the risk of development of CMV infection and all-cause mortality. Methods: This follow-up analysis is based on data from the REACT study, a multicenter prospective observational study of recipients of alloHCT who were CMV-seropositive. Production of interferon γ following ex vivo stimulation with CMV antigens IE1 (immediate early 1) and pp65 (phosphoprotein 65) was assessed by CMV ELISPOT assay at baseline and 2 and 4 weeks after transplant. Clinically significant CMV infection (CS-CMVi) was defined as CMV viremia and/or disease necessitating antiviral therapy. We evaluated the impact of CMV CMI changes on the risk of CS-CMVi and post transplant mortality. Results: The analysis included 226 recipients of alloHCT with CMV cell-mediated immunity data at baseline and 2 and/or 4 weeks after transplant. CS-CMVi occurred in 64 patients (28%). On Cox regression analyses, independent predictors of CS-CMVi included a negative Δ change from baseline to week 2 of pp65 spot counts (hazard ratio, 3.65 [95% CI, 1.65-8.04]; P = .001) to week 4 of IE1 spot counts (hazard ratio, 2.79 [95% CI, 1.46-5.35]; P = .002), anti-thymocyte globulin conditioning regimen, type of transplant, female sex, and corticosteroid use. Kaplan-Meir analysis showed a significant association of a negative IE1 change from baseline to week 4 and increased all-cause mortality after transplant (log rank test = 0.041). Conclusions: A decrease in CMV-specific T-cell responses during the first month after transplant may predict CS-CMVi and is associated with all-cause mortality in recipients of alloHCT.