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1.
Artigo em Inglês | MEDLINE | ID: mdl-38460821

RESUMO

OBJECTIVES: Allogeneic haematopoietic cell transplant (allo-HCT) recipients who are cytomegalovirus (CMV)-seronegative have better post-transplant outcomes than CMV-seropositive recipients. Letermovir (LTV) is approved for CMV primary prophylaxis in adults who are CMV-seropositive after allo-HCT, and its use is associated with improved long-term post-transplant outcomes. We analysed whether LTV has affected the relationship between CMV serostatus and post-transplant outcomes. METHODS: We conducted a retrospective single-centre cohort study of allo-HCT recipients, stratified according to donor (D) and recipient (R). CMV serostatus and the use of LTV: D-/R-, R+/LTV-, and R+/LTV+. Outcomes measured were all-cause and non-relapse mortality, clinically significant CMV infection, graft-versus-host disease, and relapse up to week 48 after allo-HCT. The D-/R- group served as the reference for comparisons in univariate, competing risk regression, and cumulative incidence functions. RESULTS: The analysis included 1071 consecutive allo-HCT recipients: 131 D-/R-, 557 R+/LTV-, and 383 R+/LTV+. All-cause mortality by day 100 was 6.1% for the D-/R- group, compared with 14.0% (p 0.024) and 7.8% (p 0.7) for the R+/LTV- and R+/LTV + groups, respectively. Non-relapse mortality by day 100 was 11.0%, 6.8% and 3.8% for R+/LTV-, R+/LTV+, and D-/R- groups, respectively, without significant difference. When including relapse as a competing event, the hazard ratio for non-relapse mortality was 1.83 (95% CI: 1.12-2.99, p 0.017) for R+/LTV- compared with D-/R- and 1.05 (95% CI 0.62-1.77, p 0.85) for R+/LTV + compared with D-/R-. DISCUSSION: CMV primary prophylaxis with LTV abrogated the mortality gap based on CMV serostatus, a protective effect that persisted after discontinuation of primary prophylaxis.

2.
Cancer Med ; 13(3): e6997, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38400683

RESUMO

OBJECTIVES: Hematological malignancy (HM) patients treated with anti-CD20 monoclonal antibodies are at higher risk for severe COVID-19. A previous single-center study showed worse outcomes in patients treated with obinutuzumab compared to rituximab. We examined this hypothesis in a large international multicenter cohort. METHODS: We included HM patients from 15 centers, from five countries treated with anti-CD20, comparing those treated with obinutuzumab (O-G) to rituximab (R-G) between December 2021 and June 2022, when Omicron lineage was dominant. RESULTS: We collected data on 1048 patients. Within the R-G (n = 762, 73%), 191 (25%) contracted COVID-19 compared to 103 (36%) in the O-G. COVID-19 patients in the O-G were younger (61 ± 11.7 vs. 64 ± 14.5, p = 0.039), had more indolent HM diagnosis (aggressive lymphoma: 3.9% vs. 67.0%, p < 0.001), and most were on maintenance therapy at COVID-19 diagnosis (63.0% vs. 16.8%, p < 0.001). Severe-critical COVID-19 occurred in 31.1% of patients in the O-G and 22.5% in the R-G. In multivariable analysis, O-G had a 2.08-fold increased risk for severe-critical COVID-19 compared to R-G (95% CI 1.13-3.84), adjusted for Charlson comorbidity index, sex, and tixagevimab/cilgavimab (T-C) prophylaxis. Further analysis comparing O-G to R-G demonstrated increased hospitalizations (51.5% vs. 35.6% p = 0.008), ICU admissions (12.6% vs. 5.8%, p = 0.042), but the nonsignificant difference in COVID-19-related mortality (n = 10, 9.7% vs. n = 12, 6.3%, p = 0.293). CONCLUSIONS: Despite younger age and a more indolent HM diagnosis, patients receiving obinutuzumab had more severe COVID-19 outcomes than those receiving rituximab. Our findings underscore the need to evaluate the risk-benefit balance when considering obinutuzumab therapy for HM patients during respiratory viral outbreaks.


Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Neoplasias Hematológicas , Humanos , Rituximab/efeitos adversos , Teste para COVID-19 , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/epidemiologia
3.
Virus Evol ; 10(1): vead086, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361816

RESUMO

Respiratory syncytial virus (RSV) infection in immunocompromised individuals often leads to prolonged illness, progression to severe lower respiratory tract infection, and even death. How the host immune environment of the hematopoietic stem cell transplant (HCT) adults can affect viral genetic variation during an acute infection is not understood well. In the present study, we performed whole genome sequencing of RSV/A or RSV/B from samples collected longitudinally from HCT adults with normal (<14 days) and delayed (≥14 days) RSV clearance who were enrolled in a ribavirin trial. We determined the inter-host and intra-host genetic variation of RSV and the effect of mutations on putative glycosylation sites. The inter-host variation of RSV is centered in the attachment (G) and fusion (F) glycoprotein genes followed by polymerase (L) and matrix (M) genes. Interestingly, the overall genetic variation was constant between normal and delayed clearance groups for both RSV/A and RSV/B. Intra-host variation primarily occurred in the G gene followed by non-structural protein (NS1) and L genes; however, gain or loss of stop codons and frameshift mutations appeared only in the G gene and only in the delayed viral clearance group. Potential gain or loss of O-linked glycosylation sites in the G gene occurred both in RSV/A and RSV/B isolates. For RSV F gene, loss of N-linked glycosylation site occurred in three RSV/B isolates within an antigenic epitope. Both oral and aerosolized ribavirin did not cause any mutations in the L gene. In summary, prolonged viral shedding and immune deficiency resulted in RSV variation, especially in structural mutations in the G gene, possibly associated with immune evasion. Therefore, sequencing and monitoring of RSV isolates from immunocompromised patients are crucial as they can create escape mutants that can impact the effectiveness of upcoming vaccines and treatments.

4.
Transplant Cell Ther ; 30(1): 114.e1-114.e16, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37775070

RESUMO

Fungal infection (FI) after allogeneic hematopoietic cell transplantation (HCT) is associated with increased morbidity and mortality. Neutropenia, HLA mismatch, graft-versus-host disease (GVHD), and viral infections are risk factors for FI. The objectives of this Center for International Blood and Marrow Transplant Research registry study were to compare the incidence and density of FI occurring within 180 days after HCT in matched sibling (Sib) transplants with either calcineurin inhibitor (CNI)-based or post-transplantation cyclophosphamide (PTCy)-based GVHD prophylaxis and related haploidentical transplants receiving PTCy, and to examine the impact of FI by day 180 on transplantation outcomes. METHODS: Patients who underwent their first HCT between 2012 and 2017 for acute myeloid leukemia, acute lymphoblastic leukemia, and myelodysplastic syndrome and received a related haploidentical transplant with PTCy (HaploCy; n = 757) or a Sib transplant with PTCy (SibCy; n = 403) or CNI (SibCNI; n = 1605) were analyzed. The incidence of FI by day 180 post-HCT was calculated as cumulative incidence with death as the competing risk. The associations of FI with overall survival, transplant-related mortality, chronic GVHD, and relapse at 2 years post-HCT were examined in Cox proportional hazards regression models. Factors significantly associated with the outcome variable at a 1% level were kept in the final model. RESULTS: By day 180 post-HCT, 56 (7%) HaploCy, 24 (6%), SibCy, and 59 (4%) SibCNI recipients developed ≥1 FI (P < .001). The cumulative incidence of yeast FI was 5.2% (99% confidence interval [CI], 3.3% to 7.3%) for HaploCy, 2.2% (99% CI, .7% to 4.5%) for SibCy, and 1.9% (99% CI, 1.1% to 2.9%) for SibCNI (P = .001), and that of mold FI was 2.9% (99% CI, 1.5% to 4.7%), 3.7% (99% CI, 91.7% to 6.6%), and 1.7% (99% CI, 1.0% to 2.6%), respectively (P = .040). FI was associated with an increased risk of death, with an adjusted hazard ratio (HR) of 4.06 (99% CI, 2.2 to 7.6) for HaploCy, 4.7 (99% CI, 2.0 to 11.0) for SibCy, and 3.4 (99% CI, 1.8 to 6.4) for SibCNI compared with SibCNI without FI (P < .0001 for all). Similar associations were noted for transplantation-related mortality. FI did not impact rates of relapse or chronic GVHD. CONCLUSIONS: Rates of FI by day 180 ranged between 1.9% and 5.2% for yeast FI and from 1.7% to 3.7% for mold FI across the 3 cohorts. The use of PTCy was associated with higher rates of yeast FI only in HaploHCT and with mold FI in both HaploHCT and SibHCT. The presence of FI by day 180 was associated with increased risk for overall mortality and transplant-related mortality at 2 years regardless of donor type or PTCy use. Although rates of FI were low with PTCy, FI is associated with an increased risk of death, underscoring the need for improved management strategies.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Micoses , Humanos , Incidência , Saccharomyces cerevisiae , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/tratamento farmacológico , Inibidores de Calcineurina/uso terapêutico , Micoses/epidemiologia , Micoses/prevenção & controle , Micoses/tratamento farmacológico , Recidiva
5.
Bone Marrow Transplant ; 59(1): 76-84, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37903992

RESUMO

Post-transplant cyclophosphamide (PTCy) is increasingly used to reduce graft-versus-host disease after hematopoietic cell transplantation (HCT); however, it might be associated with more infections. All patients who were ≥2 years old, receiving haploidentical or matched sibling donor (Sib) HCT for acute leukemias or myelodysplastic syndrome, and either calcineurin inhibitor (CNI)- or PTCy-based GVHD prophylaxis [Haploidentical HCT with PTCy (HaploCy), 757; Sibling with PTCy (SibCy), 403; Sibling with CNI-based (SibCNI), 1605] were included. Most bacterial infections occurred within the first 100 days; 953 patients (34.5%) had at least 1 infection and 352 patients (13%) had ≥2 infections. Patients receiving PTCy had a greater incidence of bacterial infections by day 180 [HaploCy 46%; SibCy 48%; SibCNI 35%; p < 0.001]. Compared with the SibCNI without infection cohort, 1.99-fold, 3.33-fold, 2.78-fold, and 2.53-fold increased TRM was seen for the HaploCy cohort without infection and HaploCy, SibCy, and SibCNI cohorts with infection, respectively. Bacterial infections increased mortality [HaploCy (HR1.84, 99% CI: 1.45-2.33, p < 0.0001), SibCy cohort (HR,1.68, 99% CI: 1.30-2.19, p < 0.0001), and SibCNI cohort (HR,1.76, 99% CI: 1.43-2.16, p < 0.0001). PTCy was associated with increased bacterial infections regardless of donor, and bacterial infections were associated with increased mortality irrespective of GVHD prophylaxis. Patients receiving PTCy should be monitored carefully for bacterial infections following PTCy.


Assuntos
Infecções Bacterianas , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Pré-Escolar , Ciclofosfamida/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Doadores de Tecidos , Inibidores de Calcineurina/uso terapêutico , Infecções Bacterianas/etiologia , Estudos Retrospectivos
6.
J Infect Dis ; 229(2): 413-421, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-37506264

RESUMO

BACKGROUND: This drug resistance analysis of a randomized trial includes 234 patients receiving maribavir and 116 receiving investigator-assigned standard therapy (IAT), where 56% and 24%, respectively, cleared cytomegalovirus DNA at week 8 (treatment responders). METHODS: Baseline and posttreatment plasma samples were tested for mutations conferring drug resistance in viral genes UL97, UL54, and UL27. RESULTS: At baseline, genotypic testing revealed resistance to ganciclovir, foscarnet, or cidofovir in 56% of patients receiving maribavir and 68% receiving IAT, including 9 newly phenotyped mutations. Among them, 63% (maribavir) and 21% (IAT) were treatment responders. Detected baseline maribavir resistance mutations were UL27 L193F (n = 1) and UL97 F342Y (n = 3). Posttreatment, emergent maribavir resistance mutations were detected in 60 (26%) of those randomized to maribavir, including 49 (48%) of 103 nonresponders and 25 (86%) of the 29 nonresponders where viral DNA initially cleared then rebounded while on maribavir. The most common maribavir resistance mutations were UL97 T409M (n = 34), H411Y (n = 26), and C480F (n = 21), first detected 26 to 130 (median 56) days after starting maribavir. CONCLUSIONS: Baseline maribavir resistance was rare. Drug resistance to standard cytomegalovirus antivirals did not preclude treatment response to maribavir. Rebound in plasma cytomegalovirus DNA while on maribavir strongly suggests emerging drug resistance. CLINICAL TRIALS REGISTRATION: NCT02931539.


Assuntos
Infecções por Citomegalovirus , Diclororribofuranosilbenzimidazol , Ribonucleosídeos , Humanos , Antivirais/uso terapêutico , Antivirais/farmacologia , Benzimidazóis/uso terapêutico , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Diclororribofuranosilbenzimidazol/análogos & derivados , DNA , Farmacorresistência Viral/genética , Ganciclovir/uso terapêutico , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Ribonucleosídeos/uso terapêutico , Transplantados
8.
Cancer Med ; 12(24): 22006-22022, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38063366

RESUMO

BACKGROUND: With the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the development of effective and safe vaccines was of utmost importance to protect vulnerable individuals, including cancer patients. Studies comparing the clinical outcomes of cancer patients with or without vaccination against coronavirus disease 2019 (COVID-19) have not demonstrated clear benefit. We aimed to determine the protective effects of COVID-19 vaccination by comparing vaccinated and unvaccinated cancer patients after the initial phase of vaccine roll-out and to identify risk factors associated with hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. METHODS: We performed a retrospective cohort study of cancer patients with COVID-19 diagnosed by polymerase chain reaction on nasal swabs between January 1, 2021 and July 30, 2021. Outcomes of interest included hospitalization, severe COVID-19, and 30-day COVID-19 attributable mortality. Univariate and multivariate analyses were performed to identify factors associated with clinical outcomes, using vaccination status as a variable of interest in all models. RESULTS: Key risk factors, such as age ≥ 60 years; comorbidities including diabetes mellitus, heart failure, and lung diseases; and specific cancer types (leukemia and lymphoma) were independently associated with hospital admission for COVID-19, severe COVID-19, and 30-day COVID-19 attributable mortality in cancer patients regardless of their vaccination status. Vaccinated patients were protected against severe COVID-19 but with no impact on hospitalization or mortality due to COVID-19. CONCLUSION: Our study highlights a significant benefit of COVID-19 vaccination for cancer patients-specifically its protection against severe COVID-19.


Assuntos
COVID-19 , Neoplasias , Humanos , Pessoa de Meia-Idade , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias , SARS-CoV-2 , Vacinas contra COVID-19 , Estudos Retrospectivos , Neoplasias/epidemiologia , Neoplasias/terapia , Vacinação
10.
J Infect Dis ; 228(11): 1549-1558, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37983000

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) on nasopharyngeal swab (NPS), remains the most reliable and practical test to diagnose coronavirus disease 2019 (COVID-19). Current literature is sparse regarding the rates of discordance between NPS and bronchoalveolar lavage (BAL) in patients with cancer. METHODS: We conducted a retrospective cohort study of adult patients with cancer who had BAL samples tested for SARS-CoV-2 at a comprehensive cancer center. Patients without NPS PCR for SARS-CoV-2 before BAL were excluded. RESULTS: In a cohort of 345 patients, 12% and 17% tested positive for SARS-CoV-2 on NPS and BAL, respectively. There was a 6.3% NPS-/BAL+ discordance rate and a 9.5% NPS+/BAL- discordance rate. Patients with lymphoma (adjusted odds ratio [aOR] = 4.06; P = .007) and Hispanic patients (aOR = 3.76; P = .009) were more likely to have NPS-/BAL+ discordance on multivariate analysis. Among patients with NPS- /BAL- for SARS-CoV-2, an alternate infectious (23%) and a noninfectious etiology (16%) were identified in BAL. CONCLUSIONS: Our discordance rates between NPS and BAL were sufficient to recommend BAL in certain patients with cancer with a high clinical suspicion of COVID-19. BAL has value in identifying alternative etiologies of illness in patients with suspected or confirmed COVID-19.


Assuntos
COVID-19 , Neoplasias , Adulto , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudos Retrospectivos , Lavagem Broncoalveolar , Teste para COVID-19 , Nasofaringe , Neoplasias/complicações , Neoplasias/diagnóstico
11.
Transpl Infect Dis ; 25 Suppl 1: e14171, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37864299

RESUMO

The preferred strategy for preventing CMV in at-risk populations in alloHCT has undergone a significant practice shift in recent years where the pendulum has swung from a pre-emptive approach to now offering letermovir prophylaxis to all CMV seropositive recipients. Letermovir prophylaxis has resulted in significant reductions in post-transplant clinically significant CMV infection (csCMVi) as well as other important outcomes such as CMV disease, resistant, and refractory CMV infections and nonrelapse mortality. However, prophylactic strategies are not without some limitations, namely delayed onset CMV infections, delayed CMV-specific T cell immune reconstitution, increased drug costs and limited data within pediatric populations. Thus, this review aims to provide an overview of prophylaxis and pre-emptive CMV preventative strategies, and how they are applicable in the current era of letermovir prophylaxis.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Criança , Humanos , Citomegalovirus , Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos
12.
Transplant Cell Ther ; 29(12): 730-738, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37783338

RESUMO

The Practice Guidelines Committee of the American Society of Transplantation and Cellular Therapy (ASTCT) partnered with its Transplant Infectious Disease Special Interest Group (TID-SIG) to update the 2009 compendium-style infectious disease guidelines for hematopoietic cell transplantation (HCT). A new approach was adopted to better serve clinical providers by publishing each standalone topic in the infectious disease series in a concise format of frequently asked questions (FAQ), tables, and figures. Experts in HCT and infectious diseases identified FAQs and then provided answers based on the strength of the recommendation and the level of supporting evidence. In the seventh guideline in the series, we focus on the respiratory syncytial virus (RSV) with FAQs addressing epidemiology, clinical diagnosis, prophylaxis, and treatment. Special consideration was given to RSV in pediatric, cord blood, haploidentical, and T cell-depleted HCT and chimeric antigen receptor T cell therapy recipients, as well as to identify future research directions.


Assuntos
Doenças Transmissíveis , Transplante de Células-Tronco Hematopoéticas , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/terapia , Transplantados , Estados Unidos
13.
Am J Infect Control ; 51(12): 1302-1308, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37804272

RESUMO

BACKGROUND: Robust infection prevention and control (IPC) measures were deployed across health care institutions at the start of the COVID-19 pandemic, resulting in increased use of personal protective equipment, enhanced contact precautions, and an emphasis on hand hygiene. Here, we evaluate the effect of enhanced IPC practices on the occurrence of various hospital-associated infections (HAIs) in a comprehensive cancer center. METHODS: From September 2016 through March 2022, we calculated the incidence rates (IRs) of HAIs for C. difficile infection, multidrug-resistant organisms, respiratory viral infections (RVIs), and device-related infections. We analyzed the incidence rate ratios for all HAIs during the periods before the pandemic, during the pandemic, at the time of the surges, and in COVID-19-designated wards. RESULTS: When comparing the prepandemic to the pandemic period, the IR across all MRDOs was similar. We observed a decrease in the IR of central line-associated bloodstream infections and a stable IR of catheter-associated urinary tract infections. A significant decrease was observed in the IR of C. difficile infection. The total IR of nosocomial RVIs decreased, as did for each respiratory virus. A similar IR of nosocomial RVIs between COVID-19 community surge versus nonsurge periods was observed except for SARS-CoV-2, RSV, and influenza. multidrug resistant organisms were 5 times more likely to occur on the COVID-19 wards compared with the non-COVID-19 wards. CONCLUSIONS: Implementing strict IPC measures during the COVID-19 pandemic in a cancer hospital led to a significant decrease in many HAIs and a reduction in nosocomial RVIs.


Assuntos
COVID-19 , Clostridioides difficile , Infecção Hospitalar , Neoplasias , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias , SARS-CoV-2 , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Hospitais , Neoplasias/complicações , Neoplasias/epidemiologia
14.
Clin Infect Dis ; 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37815489

RESUMO

BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. RESULTS: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7 to 18.0%, P<0.001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95%CI, 11.1 to 25.3%). CONCLUSION: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing.ClinicalTrials.gov Identifier: NCT04047719.

16.
Open Forum Infect Dis ; 10(8): ofad386, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37636519

RESUMO

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.

17.
Open Forum Infect Dis ; 10(4): ofad166, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37065990

RESUMO

Respiratory viral infections (RVIs) are of major clinical importance in immunocompromised patients and represent a substantial cause of morbidity and mortality in patients with hematologic malignancies and those who have undergone hematopoietic cell transplantation. Similarly, patients receiving immunotherapy with CD19-targeted chimeric antigen receptor-modified T cells, natural killer cells, and genetically modified T-cell receptors are susceptible to RVIs and progression to lower respiratory tract infections. In adoptive cellular therapy recipients, this enhanced susceptibility to RVIs results from previous chemotherapy regimens such as lymphocyte-depleting chemotherapy conditioning regimens, underlying B-cell malignancies, immune-related toxicities, and secondary prolonged, profound hypogammaglobulinemia. The aggregated risk factors for RVIs have both immediate and long-term consequences. This review summarizes the current literature on the pathogenesis, epidemiology, and clinical aspects of RVIs that are unique to recipients of adoptive cellular therapy, the preventive and therapeutic options for common RVIs, and appropriate infection control and preventive strategies.

18.
Lancet Haematol ; 10(4): e284-e294, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36990623

RESUMO

Literature discussing endemic and regionally limited infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America is scarce. This Worldwide Network for Blood and Marrow Transplantation (WBMT) article is part one of two papers aiming to provide guidance to transplantation centres around the globe regarding infection prevention and treatment, and considerations for transplantation based on current evidence and expert opinion. These recommendations were initially formulated by a core writing team from the WBMT and subsequently underwent multiple revisions by infectious disease experts and HSCT experts. In this paper, we summarise the data and provide recommendations on several endemic and regionally limited viral and bacterial infections, many of which are listed by WHO as neglected tropical diseases, including Dengue, Zika, yellow fever, chikungunya, rabies, brucellosis, melioidosis, and leptospirosis.


Assuntos
Infecções Bacterianas , Transplante de Células-Tronco Hematopoéticas , Viroses , Infecção por Zika virus , Zika virus , Humanos , Medula Óssea , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Viroses/epidemiologia , Viroses/etiologia , Viroses/prevenção & controle , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Europa (Continente)
19.
Lancet Haematol ; 10(4): e295-e305, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36990624

RESUMO

There is a scarcity of data on endemic and regionally limited fungal and parasitic infections in recipients of haematopoietic stem-cell transplantation (HSCT) outside western Europe and North America. This Worldwide Network for Blood and Marrow Transplantation (WBMT) Review is one of two papers aiming to provide guidance to transplantation centres worldwide regarding prevention, diagnosis, and treatment based on the currently available evidence and expert opinion. These recommendations were created and reviewed by physicians with expertise in HSCT or infectious disease, representing several infectious disease and HSCT groups and societies. In this paper, we review the literature on several endemic and regionally limited parasitic and fungal infections, some of which are listed as neglected tropical diseases by WHO, including visceral leishmaniasis, Chagas disease, strongyloidiasis, malaria, schistosomiasis, histoplasmosis, blastomycosis, and coccidioidomycosis.


Assuntos
Doenças Transmissíveis , Transplante de Células-Tronco Hematopoéticas , Micoses , Humanos , Medula Óssea , Micoses/epidemiologia , Micoses/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Europa (Continente)
20.
Oncology (Williston Park) ; 37(2): 69-77, 2023 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-36862845

RESUMO

COVID-19 continues to disproportionately affect patients with cancer because of their underlying immunocompromised state. Strategies to mitigate the impact of COVID-19 on patients with cancer include vaccination, which has demonstrated some level of protection, at least against serious complications such as respiratory failure and death, with limited safety concerns. In this narrative review, we discuss the current COVID-19 vaccines that are available in the United States, the published data regarding vaccine efficacy and safety in patients with cancer, current vaccination guidelines, and future directions.


Assuntos
COVID-19 , Neoplasias , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Neoplasias/complicações , Neoplasias/terapia , Pacientes , Vacinação
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