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In 2023, the EBMT Practice harmonization and Guidelines Committee partnered with the EBMT Infection Diseases Working Party (IDWP) to undertake the task of delivering best practice recommendations, aiming to harmonize by expert consensus, the already existing definitions and future epidemiological and clinical studies among centers of the EBMT network. To attain this objective, a group of experts in the field was convened. The workgroup identified and discussed some critical aspects in definitions of community-acquired respiratory viruses (CARV) and adenovirus (ADV) infections in recipient of hematopoietic cell transplant (HCT). The methodology involved literature review and expert consensus. For CARV, expert consensus focused on defining infection severity, infection duration, and establishing criteria for lower respiratory tract disease (LRTD). For ADV, the expert consensus focused on surveillance methods and the definitions of ADV infection, certainty levels of disease, response to treatment, and attributable mortality. This consensus workshop provided indications to EBMT community aimed at facilitating data collection and consistency in the EBMT registry for respiratory viral infectious complications.
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Candida lusitaniae fungemia is a serious infection that is rarely reported in children. The aim of this study is to describe a case series of C. lusitaniae fungemia and review previous publications regarding this rare pathogen. This is a multicenter case series of children diagnosed with C. lusitaniae fungemia. A total of 18 cases that occurred over a 15-year period in five tertiary hospitals were included. Additionally, a review of the literature regarding C. lusitaniae fungemia in children was performed. A total of 18 cases were enrolled; 11/18 (61%) were males, with a mean age of 2.3 years. All patients had severe underlying diseases and risk factors for opportunistic infection, most commonly prematurity and malignancies. More than one-third of cases occurred during the last 2 years of the study period. All isolates were susceptible to all tested antifungals. The survival rate following the acute infection was 94%, whereas the survival rate of 14 previously published cases was 71%, with the most common underlying diseases being CGD and malignancies. Candida lusitaniae fungemia is not a common event in the pediatric population, occurring exclusively in children with severe underlying diseases and significant risk factors. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents; variability in susceptibility as previously reported was not found in this study. The allegedly higher rate of infection in recent years is in need of further investigation in larger prospective studies in order to conclude if a real trend is at play.
Candida lusitaniae fungemia is a serious infection rarely reported in children. This cohort revealed better clinical outcomes than previously reported. All tested isolates were susceptible to all antifungal agents. The higher rate of infection in recent years is in need of further investigation.
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Antifúngicos , Candida , Pré-Escolar , Feminino , Humanos , Masculino , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/genética , Candida/isolamento & purificação , Candida/patogenicidade , Candidemia/microbiologia , Candidemia/epidemiologia , Fungemia/microbiologia , Fungemia/mortalidade , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
OBJECTIVES: Nocardiosis is a rare but life-threatening infection after hematopoietic cell transplantation (HCT). We aimed at identifying risk factors for nocardiosis after allogeneic HCT and clarifying the effect of trimethoprim-sulfamethoxazole prophylaxis on its occurrence. METHODS: We performed a retrospective multicenter case-control study of patients diagnosed with nocardiosis after allogeneic HCT between January 2000 and December 2018. For each case, two controls were matched by center, transplant date, and age group. Multivariable analysis was conducted using conditional logistic regression to identify potential risk factors for nocardiosis. Kaplan-Meier survival curves of cases and controls were compared using log-rank tests. RESULTS: Sixty-four cases and 128 controls were included. Nocardiosis occurred at a median of 9 months after allogeneic HCT (interquartile range: 5-18). After adjustment for potential confounders in a multivariable model, Nocardia infection was associated with tacrolimus use (adjusted odds ratio [aOR] 9.9, 95 % confidence interval [95 % CI]: 1.6-62.7), lymphocyte count < 500/µL (aOR 8.9, 95 % CI: 2.3-34.7), male sex (aOR 8.1, 95 % CI: 2.1-31.5), recent use of systemic corticosteroids (aOR 7.9, 95 % CI: 2.2-28.2), and recent CMV infection (aOR 4.3, 95 % CI: 1.2-15.9). Conversely, use of trimethoprim-sulfamethoxazole prophylaxis was associated with a significantly decreased risk of nocardiosis (aOR 0.2, 95 % CI: 0.1-0.8). HCT recipients who developed nocardiosis had a significantly decreased survival, as compared with controls (12-month survival: 58 % and 90 %, respectively; p < 0.0001). CONCLUSIONS: We identified six factors independently associated with the occurrence of nocardiosis among allogeneic HCT recipients. In particular, trimethoprim-sulfamethoxazole prophylaxis was found to protect against nocardiosis.
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Transplante de Células-Tronco Hematopoéticas , Nocardiose , Combinação Trimetoprima e Sulfametoxazol , Humanos , Nocardiose/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Feminino , Estudos de Casos e Controles , Fatores de Risco , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Transplante Homólogo/efeitos adversos , Idoso , Transplantados/estatística & dados numéricos , Nocardia/isolamento & purificação , AntibioticoprofilaxiaRESUMO
Listeriosis is rare after hematopoietic stem cell transplantation (HCT). Little is known about listeriosis in this population. In this retrospective international case-control study, we evaluated 41 listeriosis episodes occurring between 2000 and 2021 in HCT recipients (111 transplant centers in 30 countries) and assessed risk factors for listeriosis by comparisons with matched controls. The 41 listeriosis episodes (all due to Listeria monocytogenes [LM]) occurred in 30 allogeneic (allo)-HCT recipients and 11 autologous (auto)-HCT recipients at a median of 6.2 months (interquartile range [IQR], 1.6 to 19.3 months) post-HCT. The estimated incidence was 49.8/100,000 allo-HCT recipients and 13.7/100,000 auto-HCT recipients. The most common manifestations in our cohort were fever (n = 39; 95%), headache (n = 9; 22%), diarrhea, and impaired consciousness (n = 8 each; 20%). Four patients (10%) presented with septic shock, and 19 of 38 (50%) were severely lymphocytopenic. Thirty-seven patients (90%) had LM bacteremia. Eleven patients (27%) had neurolisteriosis, of whom 4 presented with nonspecific signs and 5 had normal brain imaging findings. Cerebrospinal fluid analysis revealed high protein and pleocytosis (mainly neutrophilic). Three-month mortality was 17% overall (n = 7), including 27% (n = 3 of 11) in patients with neurolisteriosis and 13% (n = 4 of 30) in those without neurolisteriosis. In the multivariate analysis comparing cases with 74 controls, non-first HCT (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.10 to 30.82; P = .038); and lymphocytopenia <500 cells/mm3 (OR, 7.54; 95% CI, 1.50 to 37.83; P = .014) were significantly associated with listeriosis. There were no statistically significant differences in background characteristics, immunosuppression, and cotrimoxazole prophylaxis between cases and controls. HCT recipients are at increased risk for listeriosis compared to the general population. Listeriosis cause severe disease with septic shock and mortality. Neurolisteriosis can present with nonspecific signs and normal imaging. Lymphocytopenia and non-first HCT are associated with an increased risk of listeriosis, and cotrimoxazole was not protective.
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Transplante de Células-Tronco Hematopoéticas , Listeria monocytogenes , Listeriose , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Estudos de Casos e Controles , Listeriose/epidemiologia , Listeria monocytogenes/isolamento & purificação , Adulto , Idoso , Europa (Continente)/epidemiologia , IncidênciaRESUMO
BACKGROUND: Enterococcal meningitis in children is rare, and its clinical presentation, laboratory characteristics and outcomes are not well defined. METHODS: We conducted a retrospective analysis of Enterococcal meningitis cases during 2002-2023 at our tertiary center. RESULTS: We identified 10 cases in children 2 weeks to 15 years old (median age: 8 months). Seven children were males and 9 had comorbidities, including a ventriculoperitoneal shunt in 5 children. All children with shunt infections presented with nonspecific signs and symptoms. While 8 children presented with fever, only 3 had signs of meningeal irritation and altered consciousness. Cerebrospinal fluid pleocytosis was evident in almost all children with a median of 173 cells/mL. Nine cases were due to Enterococcus faecalis , and 1 case was due to E. faecium . All 5 children with ventriculoperitoneal shunt underwent shunt removal and replacement. All children recovered without documented sequelae. CONCLUSIONS: Enterococcal meningitis is rare, especially in healthy neonates. It typically occurs following neurosurgical interventions and may only present with fever and shunt malfunction, without overt meningeal signs and with mild inflammation. The prognosis is favorable.
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Infecções por Bactérias Gram-Positivas , Centros de Atenção Terciária , Humanos , Lactente , Pré-Escolar , Estudos Retrospectivos , Criança , Feminino , Masculino , Adolescente , Centros de Atenção Terciária/estatística & dados numéricos , Recém-Nascido , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/diagnóstico , Derivação Ventriculoperitoneal/efeitos adversos , Meningites Bacterianas/microbiologia , Meningites Bacterianas/epidemiologia , Enterococcus faecalis/isolamento & purificação , Antibacterianos/uso terapêutico , Enterococcus faeciumRESUMO
Invasive fungal infections (IFI) cause morbidity and mortality in children with acute leukemia (AL). We retrospectively collected data on febrile neutropenic episodes (FNE) in AL children (2016-2021) and assessed factors associated with proven/probable IFI. Ninety-three children developed 339 FNE. Seventeen (18.3%) children developed 19 proven/probable IFI (11 yeast; eight molds). The proven/probable yeast IFI rate was 6/52 (11.5%) in children who belong to the high risk for IFI category (HR-IFI-AL: high-risk acute lymphocytic leukemia (ALL), acute myeloid leukemia, relapse); and 5/41 (12.2%) in the non-HR-IFI-AL category (standard/intermediate risk ALL). The proven/probable mold IFI rate was 7/52 (13.5%) in HR-IFI-AL children and 1/41 (2.4%) in the non-HR-IFI-AL category. In the multivariable analysis, underlying genetic syndrome, oral mucositis, and older age were significantly associated with proven/probable IFI, while a longer time since AL diagnosis was protective. Two of 13 (15.4%) HR-IFI-AL children died because of IFI. The elevated risks of proven/probable mold IFI and the associated mortality in HR-IFI-AL children, and high risk of invasive candidiasis in the non-HR-IFI-AL group, emphasize the need for the close monitoring of local epidemiology and the adjustment of practices accordingly.
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Patients can be immunocompromised from a diverse range of disease and treatment factors, including malignancies, autoimmune disorders and their treatments, and organ and stem-cell transplantation. Infections are a leading cause of morbidity and mortality in immunocompromised patients, and the disease treatment landscape is continually evolving. Despite being a critical but preventable and curable adverse event, the reporting of infection events in randomised trials lacks sufficient detail while inconsistency of categorisation and definition of infections in observational and registry studies limits comparability and future pooling of data. A core reporting dataset consisting of category, site, severity, organism, and endpoints was developed as a minimum standard for reporting of infection events in immunocompromised patients across study types. Further additional information is recommended depending on study type. The standardised reporting of infectious events and attributable complications in immunocompromised patients will improve diagnostic, treatment, and prevention approaches and facilitate future research in this patient group.
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Transplante de Células-Tronco Hematopoéticas , Humanos , Consenso , Hospedeiro ImunocomprometidoRESUMO
The aim of this study was to determine the current approach of EBV-driven post-transplant complications in context of monitoring, diagnosis, prevalence and treatment in EBMT transplant centers. Routine serology testing in patient and donor before HCT is performed in 95.5% centers. Pretransplant EBV-DNA is routinely tested in all patients in 32.7% centers. Monitoring for EBV infection is feasible in 98.2% centers: including 66.7% centers using standardized PCR. Post-HCT regular monitoring is performed in all patients in 80.5% centers. Anti-EBV prophylaxis with rituximab is used in 12.4% centers. Frequency of csEBV-DNA-emia was 7.4% (adults: 6.2%, children: 12.6%). The PCR threshold used to start preemptive treatment was differentiated among centers. Frequency of EBV-PTLD was 1.6% (adults: 1.3%; children: 3.5%). First-line therapy of EBV-driven complications was rituximab and reduction of immunosuppressive therapy. The rate of failure of first-line preemptive treatment was 12.0%. EBV-specific viral-specific T-lymphocytes were available in 46.0% centers. A number of new experimental therapies were given in 28 patients with resistant/refractory PTLD. In conclusion, the prevalence of EBV-DNA-emia and EBV-PTLD over the period 2020-2021 decreased in comparison to historical data. New trends (routine pretransplant screening for EBV-DNA, wider access to VST, new experimental therapies) are being observed in management of EBV infection after allo-HCT.
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Doenças Transmissíveis , Infecções por Vírus Epstein-Barr , Transtornos Linfoproliferativos , Criança , Adulto , Humanos , Herpesvirus Humano 4/genética , Rituximab/uso terapêutico , Prevalência , DNA Viral , Infecções por Vírus Epstein-Barr/epidemiologia , Transtornos Linfoproliferativos/etiologia , Carga ViralRESUMO
BACKGROUND: Human metapneumovirus (hMPV) epidemiology, clinical characteristics and risk factors for poor outcome after allogeneic stem cell transplantation (allo-HCT) remain a poorly investigated area. METHODS: This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allo-HCT. RESULTS: We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. CONCLUSIONS: These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases.
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Transplante de Células-Tronco Hematopoéticas , Linfopenia , Metapneumovirus , Infecções por Paramyxoviridae , Infecções Respiratórias , Adulto , Humanos , Estudos de Coortes , Estudos Retrospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Infecções Respiratórias/tratamento farmacológico , Infecções por Paramyxoviridae/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Corticosteroides/uso terapêuticoRESUMO
Background: Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed. Methods: We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints. Findings: 1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2-26.0) and 11.2% (9.6-13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2-3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3-68.9] vs. 70.4 [67.9-72.8]; multivariate HR 1.5 [1.1-2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8-77.4] vs. 79.0% [76.7-81.1]; multivariate HR 1.7 [1.1-2.5]; p = 0.01). Interpretation: Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure. Funding: There was no external funding source for this study.
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Candida spp. can cause bloodstream infection and is associated with significant mortality. The proportion of fluconazole-resistant Candida non-albicans has increased over the years, and empirical fluconazole maybe inappropriate. In this retrospective study, we analyzed clinical characteristics, antifungal resistance patterns, and mortality in children with candidemia treated at a tertiary medical center in Jerusalem between 2009 and 2022. A total of 122 children developed 127 candidemia episodes with 132 Candida isolates. Half the episodes occurred in immunocompromised children. Septic shock was present in 27 (21.3%). Candida non-albicans was responsible for 71/132 (56.5%) episodes; 16/132 (12.1%) of isolates were fluconazole-resistant. The rate of Candida non-albicans was significantly higher in fluconazole-resistant episodes (90 vs. 50.5%, p = 0.02). Prolonged severe neutropenia and previous fluconazole exposure were more frequent in fluconazole-resistant episodes. Thirty-day mortality was 25 (19.7%). Greater mortality, as shown by multivariate analysis, was associated with candidemia contracted in the pediatric intensive care unit (PICU), previous use of azoles or carbapenems, and in the presence of shock. In conclusion, mortality rates in our study were higher than those previously reported. In suspected infection associated with factors which we found to increase the probability of mortality-PICU admission, shock, and earlier azole or carbapenems exposure-empirical antifungals should be considered.
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OBJECTIVES: The gastrointestinal (GI) tract is a major human adenovirus (HAdV) replication site in patients undergoing hematopoietic stem cell transplantation (HSCT), yet the prevalence and correlates of HAdV GI infection in this setting have remained poorly recognized, especially among adult HSCT recipients. DESIGN OR METHODS: We retrospectively studied the prevalence and risk factors of HAdV GI-tissue infection in HSCT recipients (73 adults and 15 children) with GI symptoms who underwent GI-tissue biopsy between January-2012 and December-2017. The presence of HAdV in the GI tissues was determined by real-time PCR. RESULTS: HAdV GI-tissue infection was detected in 21 (23.9%) patients, with similar infection rates identified in adults and children. GI-tissue detection was more common at late (>100 days) compared to early times post-transplantation (50% vs. 12.9%, p < .001). The presence of bloody diarrhea, Arab ethnicity (p = .014) and concurrent cytomegalovirus GI-tissue detection (p = .025) were significantly correlated with HAdV GI-tissue infection, while chronic graft versus host disease was of borderline association (p = .055). CONCLUSIONS: Our findings reveal a high rate and new clinical-demographic correlates of HAdV GI-tissue infection in adult and pediatric HSCT recipients with GI symptoms. The findings highlight the need for future prospective studies to assess the relatedness of HAdV infection to the GI symptoms, and the prevalence, impact, and treatment of HAdV GI infection in HSCT recipients.
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Infecções por Adenoviridae , Infecções por Adenovirus Humanos , Adenovírus Humanos , Transplante de Células-Tronco Hematopoéticas , Adulto , Humanos , Criança , Adenoviridae/genética , Estudos Retrospectivos , Estudos Prospectivos , Infecções por Adenoviridae/diagnóstico , Infecções por Adenoviridae/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Infecções por Adenovirus Humanos/diagnóstico , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/etiologia , Adenovírus Humanos/genética , BiópsiaRESUMO
Background: Hematopoietic stem cell transplantation (HSCT) is the only curative option for many nonmalignant hematopoietic-derived diseases in pediatric patients. Survival after HSCT has improved in recent years and resulted in a 90% survival rate and cure in some nonmalignant diseases. Graft-vs.-host disease (GVHD) remains a frequent and major complication of HSCT, and a leading cause of morbidity and mortality. Prognosis of patients with high-grade GVHD is dismal, with survival rates varying from 25% in the adult population to 55% in pediatric patients. Methods: The main aim of this study is to evaluate the incidence, risk factors, and outcome of severe acute GVHD (AGVHD) in pediatric patients with nonmalignant diseases, following allogeneic HSCT. Clinical and transplant data were retrospectively collected for all pediatric patients who underwent allogeneic HSCT for nonmalignant diseases at the Hadassah Medical Center between 2008 and 2019. Patients who developed severe AGVHD were compared with those who did not. Results: A total of 247 children with nonmalignant diseases underwent 266 allogeneic HSCTs at Hadassah University Hospital over an 11-year period. Seventy-two patients (29.1%) developed AGVHD, 35 of them (14.1%) severe AGVHD (grade 3-4). Significant risk factors for developing severe AGVHD were unrelated donor (p < 0.001), mismatch donor (p < 0.001), and the use of peripheral blood stem cells (PBSCs) (p < 0.001). Survival rates of pediatric patients with severe AGVHD was 71.4%, compared with 91.9% among those with mild (grade 1-2) AGVHD and 83.4% among patients without AGVHD (p = 0.067). Conclusions: These results demonstrate a high survival rate in pediatric patients with nonmalignant diseases despite severe GVHD. Significant mortality risk factors found in these patients were the source of donor PBSC (p = 0.016) and poor response to steroid treatment (p = 0.007).
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We investigated the incidence and outcome of anti-CD19 chimeric antigen receptor (CAR) T-cells-associated Common Terminology Criteria for Adverse Events (CTCAE) ≥grade 3 cytopenia. In the EBMT CAR-T registry, we identified 398 adult patients with large B-cell lymphoma who had been treated with CAR-T-cells with axicel (62%) or tisacel (38%) before August 2021 and had cytopenia status documented for the first 100 days. Most patients had received two or three previous lines of therapy, however, 22.3% had received four or more. Disease status was progressive in 80.4%, stable in 5.0% and partial/complete remission in 14.6%. 25.9% of the patients had received a transplantation before. Median age was 61.4 years (min-max; IQR=18.7-81; (52.9-69.5)).The cumulative incidence of ≥grade 3 cytopenia was 9.0% at 30 days (95% CI (6.5 to 12.1)) and 12.1% at 100 days after CAR T-cell infusion (95% CI (9.1 to 15.5)). The median time from CAR-T infusion to cytopenia onset was 16.5 days (min-max; IQR=1-90; (4-29.8)). Grade 3 and grade 4 CTCAE cytopenia occurred in 15.2% and 84.8%, respectively. In 47.6% there was no resolution.Severe cytopenia had no significant impact on overall survival (OS) (HR 1.13 (95% CI 0.74 to 1.73), p=0.57). However, patients with severe cytopenia had a poorer progression-free survival (PFS) (HR 1.54 (95% CI 1.07 to 2.22), p=0.02) and a higher relapse incidence (HR 1.52 (95% CI 1.04 to 2.23), p=0.03). In those patients who developed severe cytopenia during the first 100 days (n=47), OS, PFS, relapse incidence and non-relapse mortality at 12 months after diagnosis of severe cytopenia were 53.6% (95% CI (40.3 to 71.2)), 20% (95% CI (10.4 to 38.6)), 73.5% (95% CI (55.2 to 85.2)) and 6.5% (95% CI (1.7 to 16.2)), respectively.In multivariate analysis of severe cytopenia risk factors, only year of CAR-T infusion (HR=0.61, 95% CI (0.39 to 0.95), p=0.028) and total number of treatment lines before CAR-T infusion (one or two lines vs three or more, HR=0.41, 95% CI (0.21 to 0.83), p=0.013) had a significant positive association with the incidence of cytopenia. Other factors, such as previous transplantation, disease status at time of CAR-T, patient age and patient sex, had no significant association.Our data provide insight on frequency and clinical relevance of severe cytopenia after CAR T-cell therapy in the European real-world setting.
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Anemia , Receptores de Antígenos Quiméricos , Adulto , Humanos , Pessoa de Meia-Idade , Imunoterapia Adotiva/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia/etiologia , Antígenos CD19RESUMO
Introduction: COVID-19 has been associated with high morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HCT) recipients. Methods: This study reports on 986 patients reported to the EBMT registry during the first 29 months of the pandemic. Results: The median age was 50.3 years (min - max; 1.0 - 80.7). The median time from most recent HCT to diagnosis of COVID-19 was 20 months (min - max; 0.0 - 383.9). The median time was 19.3 (0.0 - 287.6) months during 2020, 21.2 (0.1 - 324.5) months during 2021, and 19.7 (0.1 - 383.9) months during 2022 (p = NS). 145/986 (14.7%) patients died; 124 (12.6%) due to COVID-19 and 21 of other causes. Only 2/204 (1%) fully vaccinated patients died from COVID-19. There was a successive improvement in overall survival over time. In multivariate analysis, increasing age (p<.0001), worse performance status (p<.0001), contracting COVID-19 within the first 30 days (p<.0001) or 30 - 100 days after HCT (p=.003), ongoing immunosuppression (p=.004), pre-existing lung disease (p=.003), and recipient CMV seropositivity (p=.004) had negative impact on overall survival while patients contracting COVID-19 in 2020 (p<.0001) or 2021 (p=.027) had worse overall survival than patients with COVID-19 diagnosed in 2022. Discussion: Although the outcome of COVID-19 has improved, patients having risk factors were still at risk for severe COVID-19 including death.
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COVID-19 , Doenças Transmissíveis , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Pessoa de Meia-Idade , Medula Óssea , Transplante Homólogo , COVID-19/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças Transmissíveis/complicações , Infecções por Citomegalovirus/complicações , Sistema de RegistrosRESUMO
Hematopoietic stem cell transplant (HSCT) recipients may be at high risk of mortality from coronavirus disease 2019 (COVID-19). However, specific data on COVID-19 after treatment with HSCT in patients affected by autoimmune diseases (ADs) are still lacking. In this multicenter observational study of the European Society for Blood and Marrow Transplantation (EBMT), clinical data on COVID-19 in 11 patients affected by severe ADs treated with HSCT (n = 3 allogeneic transplant; n = 8 autologous transplant) are reported. All patients were symptomatic during the initial phase of the SARS-CoV-2 infection. At screening, 5 patients reported upper respiratory symptoms, 3 patients had cough without oxygen requirement, and 6 patients exhibited extra-pulmonary symptoms. Four cases developed a lower respiratory tract disease (LRTD). Hospitalization was required in 6 cases, without necessity of intensive care unit (ICU) admission and/or ventilation/supplemental oxygen. Different interventions were adopted: remdesivir (n = 1), nirmatrelvir/ritonavir (n = 1), sotrovimab (n = 1), immunoglobulins (n = 1). At last follow-up, all patients are alive and had resolution of the infection. The current analysis describing the mild-moderate course of COVID-19 in transplant recipients affected by ADs, similar to the course observed in ADs under standard treatments, provides useful information to support the delivery of HSCT programs in this field. Vaccination and new treatments available for SARS-CoV-2 may be useful to further minimize the risk of infection.
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Doenças Autoimunes , COVID-19 , Transplante de Células-Tronco Hematopoéticas , Humanos , SARS-CoV-2 , RNA Viral , Transplantados , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/terapiaRESUMO
Risk factors for severe SARS-Cov-2 infection course are poorly described in children following hematopoietic cell transplantation (HCT). In this international study, we analyzed factors associated with a severe course (intensive care unit (ICU) admission and/or mortality) in post-HCT children. Eighty-nine children (58% male; median age 9 years (min-max 1-18)) who received an allogeneic (85; 96%) or an autologous (4; 4%) HCT were reported from 28 centers (18 countries). Median time from HCT to SARS-Cov-2 infection was 7 months (min-max 0-181). The most common clinical manifestations included fever (37; 42%) and cough (26; 29%); 37 (42%) were asymptomatic. Nine (10%) children following allo-HCT required ICU care. Seven children (8%) following allo-HCT, died at a median of 22 days after SARS-Cov-2 diagnosis. In a univariate analysis, the probability of a severe disease course was higher in allo-HCT children with chronic GVHD, non-malignant disease, immune suppressive treatment (specifically, mycophenolate), moderate immunodeficiency score, low Lansky score, fever, cough, coinfection, pulmonary radiological findings, and high C-reactive protein. In conclusion, SARS-Cov-2 infection in children following HCT was frequently asymptomatic. Despite this, 10% needed ICU admission and 8% died in our cohort. Certain HCT, underlying disease, and SARS-Cov-2 related factors were associated with a severe disease course.
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COVID-19 , Doenças Transmissíveis , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Criança , Feminino , Transplante Homólogo , Estudos Prospectivos , Medula Óssea , Teste para COVID-19 , Tosse/etiologia , COVID-19/etiologia , SARS-CoV-2 , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fatores de Risco , Progressão da Doença , Doenças Transmissíveis/etiologiaRESUMO
The management of cytomegalovirus (CMV) infection was assessed with a survey performed in 2020 by the Infectious Diseases Working Party of European Society for Blood and Marrow Transplantation (EBMT). One-hundred-eighty of the 579 EBMT centres (31%) responded. CMV monitoring with quantitative PCR for CMV-DNAemia was used by 97% of centres while the duration of monitoring was variable according to the patient immune recovery and the ongoing immunosuppressive therapy. CMV prophylaxis for high-risk patients was used in 101 (56%) of centres: letermovir in 62 centres (61%), aciclovir/valaciclovir in 19 centres (19%), ganciclovir/valganciclovir in 17 centres (17%), foscarnet in 3 (3%). The most used trigger for pre-emptive therapy was a threshold of >103 copies/ml or >103 IU/ml. Ganciclovir/valganciclovir confirmed the preferred first line treatment both for pre-emptive and CMV disease therapy. CMV-cytotoxic T-cells were used mainly in the setting of relapsing/refractory CMV disease. Forty-eight centres reported CMV refractory/resistant infection due to mutated CMV strain.This survey showed that letermovir prophylaxis is adopted by more than half of centres using a prophylaxis approach for CMV infection. How letermovir prophylaxis will modify other important pillars of daily CMV management, such as frequency of CMV-DNAemia monitoring and preemptive therapy, remain a matter of investigation.
Assuntos
Doenças Transmissíveis , Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Valganciclovir , Antivirais/farmacologia , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças Transmissíveis/etiologiaRESUMO
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is an efficient treatment for numerous malignant and nonmalignant conditions affecting children. This procedure can result in infectious and noninfectious neurological complications (NCs). Objective: The objective of the study is to examine the incidence, risk factors, and outcomes of NCs in pediatric patients following allogeneic HSCT. Methods: We performed a retrospective study of 746 children who underwent 943 allogeneic HSCTs in two large pediatric hospitals in Israel from January 2000 to December 2019. Results: Of the pediatric patients 107 (14.3%) experienced 150 NCs. The median follow-up was 55 months. Noninfectious NCs were more common than infectious NCs (81.3% vs. 18.7%). Factors significantly associated with type of NC (infectious vs. noninfectious) were underlying disease (immunodeficiency vs. malignant and metabolic/hematologic disease) (p-value = 0.000), and use of immunosuppressive agent, either Campath or ATG (p-value = 0.041). Factors with a significant impact on developing neurological sequelae post-NC were number of HSCT >1 (p-value = 0.028), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.003), and infectious type of NC (p-value = 0.046). The overall survival rate of whole NC-cohort was 44%; one-third of all mortality cases were attributed to the NC. The strongest prognostic factors associated with mortality were older age at HSCT (p-value = 0.000), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.004), and the existence of neurological sequelae (p-value = 0.000). Abnormal central nervous system imaging (p-value = 0.013), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.019), and neurological sequelae (p-value = 0.000) had statistically significant effects on neurological cause of death. Conclusion: Infectious and noninfectious NCs are a significant cause of morbidity and mortality following allogeneic HSCT in children. Further research is required to better understand the risk factors for different NCs and their outcomes regarding sequelae and survival.