A mucormicose é uma infecção rara, porém altamente invasiva, causada por fungo da classe dos zigomicetos, ordem Mucorales e Entomophtorales. É causada por patógenos oportunistas e está associada às ...doenças hematológicas devido ao imunocomprometimento. Possui um curso clínico fulminante e grave, devido ao rápido crescimento do fungo e a destruição de tecidos adjacentes, demandando diagnóstico precoce e tratamento clínico/cirúrgico breve. A mucormicose na forma rinocerebroorbitária é associada à piores prognósticos e quase que exclusivamente observadas em pacientes imunocomprometidos. Neste relato de caso, uma paciente do gênero feminino de 53 anos com diagnóstico de LMA secundária à SMD, tratada com daunorrubicina e citarabina, foi internada no setor de hematologia com edema de face, neutropenia febril e leve parestesia em hemiface esquerda, sendo posteriormente diagnosticada como sinusite e celulite periorbitária, com drenagem de secreção pela rinofaringe e orofaringe. Em maio de 2021, paciente foi diagnosticada com mucormicose em região periorbitária, acometendo também cavidade nasal e seio maxilar esquerdo. Apresentou leucograma de 1510 leucócitos sendo 408 neutrófilos em sangue periférico. Durante a avaliação odontológica foi visualizado pequeno nódulo de consistência fibrosa, de aproximadamente 0,1cm de extensão, de coloração amarelada, na região de gengiva inserida do primeiro pré-molar superior esquerdo, quando foi sugerido e realizado uma radiografia panorâmica e tomografia computadorizada de feixe cônico para definir a extensão da lesão. Foi realizada cultura sugerindo diagnóstico de infecção fúngica compatível com mucormicose. Foi iniciado o tratamento com Isavuconazol e Levofloxacino. A paciente evoluiu para óbito decorrente de síndrome respiratória aguda grave-Covid-19. Conclui-se que a abordagem multiprofissional no diagnóstico dos pacientes com doenças onco-hematológicas faz-se necessário para instituir o correto tratamento e acompanhamento das doenças.
Objectives: T-cell Brazil project started in April 2017 focusing to collecting epidemiological and clinical data from the most frequent subtypes of PTCL, as an ambispective study collected diagnosis ...data from January 2015 to December 2022. Our goals were to obtain the frequency of subtypes and the clinical and biology characteristic from five Brazilian regions; besides to have a routine pathological revision and to evaluate the Overall Survival (OS), Progression-Free Survival (PFS) in 5 years of follow-up. Method: After 39 centers were approved by their Ethical Committee, they registered their cases using the REDcap Platform by Vanderbilt, being 63% public centers. Here, It was just analyzed a Prospective Cohort (PC), with diagnosis date from April 2017 to December 2022, a total of 461 cases. Descriptive analyses, Kaplan-Meier method, Log-Rank test to compare groups and Cox Regression to identify risk factor for OS using IBM-SPSS software v.24. Results: The median age was 52 years (18-92); 58% male; Almost 72% had advanced stages, 25% ECOG ≥ 2; the distribution of main subtypes was: 30% PTCL-NOS; 18% ALCL, ALK-; 14% ATL; 13% ENKTL-NT; 10.5% AITL; 5% ALCL, ALK+; 9.5% others. A median of follow up of 22 months (0-73), 55% pts were alive and 24-month PFS and OS were 36% and 49%, respectively. OS by main subtypes was 69% ALCL, ALK+; 61% ALCL, ALK; 50% PTCL-NOS; 44% ENKTL-NT; 41% AITL; 27% ATL. Cox regression showed ATL (HR 1.6, p = 0.008), ECOG ≥ 2 (HR 1.86, p < 0.0001) and Ann Arbor Stage III-IV (HR 2.06, p < 0.0001) as bad prognosis for OS; whereas for PFS were ATL (HR 1.9, p < 0.0001); ECOG≥ 2 (HR 1.53, p = 0.002); Ann Arbor Stage III-IV (HR 1.75, p = 0.001) and B symptoms (HR 1.36, p = 0.02). Discussion: PTCL make up approximately 10-15% of lymphoid malignancies and its frequency varies geographically. In Brazil, mainly due to its vast dimension, data collection has limitations and is subject to bias. This is the first experience cover all over the country, focusing also an educational and of interchanging experience network among the multidisciplinary health team in Brazil. Conclusions: Our initial target of 500 pts exceeded, hence the number of prospective cohort is getting close, because we are in a consistency data phase and probably more cases will be available after that. So, it is possible to make analyzes with PC. ATL and ENKTL-NT subtype presented more frequent of all, different of the Occidental countries, but similar with recent data from American Latin.
Objectives: To evaluate number of extranodal (EN) sites in nodal PTCL lymphomas (PTCL-NOS, TFH and ALCL ALK+/ALK-) and its specific location as a surrogate for overall survival (OS) and progression ...free survival (PFS). Also generate hypothesis for further molecular analysis. Material and methods: T-cell Brazil project is a national, ambispective study of patients (pts) with histological diagnosis of PTCL diagnosed from January 2015 to December 2022. Approval for the study was obtained at the coordinating center (Samaritano Hospital – São Paulo) and at each participating center. Inclusion criteria was previously untreated patients age ≥ 19 years, with de novo PTCL lymphoma. Clinical information, initial therapy and response, subsequent therapies, along with survival status and cause of death were collected. Treatment outcome was determined by OS and PFS. REDcap Platform (by Vanderbilt) has been used to collect and store data and for analysis the IBM-SPSS v. 24 was applied. Kaplan-Meier method estimated the OS and PFS, whereas Log-Rank tests to compare its curves. This trial is registered at Clinical trials (NCT03207789). Results: Of 621 registered we selected 198 patients (pts) diagnosed with nodal PTCL with at least one EN involvement. Considering all 198 pts, there was a slight male predominance (63%); median age 53 years; 79% were staged III or IV; 81.5 were IPI 2 or more. Most frequently histology was PTCL-NOS (46%), followed by ALCL ALK+ (32%), ALCL ALK- (12.5%) and TFH (9.5%). The majority had B Symptoms (63%); 37.5% had Bone Marrow infiltration. The chemotherapy most frequently chosen were CHOEP (54.5%) followed by CHOP (19.5%); Transplant as consolidation was in 20% of the cases. Almost half of pts achieved complete response after first line (44%), although 38% relapsed. Cohort 1 (E N = 1) and 2 (EN 32) were similar regarding clinical characteristics, except, for stage III-IV (73% vs 96%; p <.0001); IPI 33 (37.5% vs. 82%; p <.0001) and ECOG (22 vs. 48%; p = .001), respectively. Therefore, translating in a more advanced disease in Cohort 2. The most common extranodal location in Cohort 1 was Skin/ Subcutaneous (35%), followed by gastrointestinal tract (18%) and lung (16%). NHL-T subtypes behaved similarly in this EN exploratory analysis, with a better OS and PFS in ALCL ALK+, followed by ALK- and PTCL-NOS. There was no difference in PFS in Cohort 1 and 2, but there was a slight difference in OS (55% vs. 42% in 12 months; p = 0.06), suggesting EN sites involvement assessed by CT and PET-CT as possible surrogate for outcomes in this population. Discussion: PTCL lymphomas account for 10-15% of all NHL. They are a heterogeneous group of infrequent neoplasms with a variable clinical course but prevalently aggressive behavior and high mortality rates. Despite IPI (International Prognostic Index) that include EN site in its variables, lack is known regarding EN location or impact on prognosis. Conclusion: NHL-T is still unmet medical need considering suboptimal outcome in treatment and survival. New biological and clinical finding are still necessary to adequate stratify this group of pts, considering poor performance of IPI and PIT scores. Number and location of EN sites involvement may be a possible surrogate for outcome, which can be a reflect of a distinct biology, that needs further investigation. Registries are of importance considering rarity and poor prognosis of this diseases and an adequate instrument to hypothesis generation.
Recipients of autologous haemopoietic stem-cell transplants (auto-HSCT) have an increased risk of herpes zoster and herpes zoster-related complications. The aim of this study was to establish the ...efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT.
In this randomised, double-blind, placebo-controlled phase 3 trial, participants were recruited from 135 medical centres (ie, stem-cell transplant centres and hospitals) in North America, South America, Europe, and Asia. Patients were eligible if they were aged 18 years or older, scheduled to receive an auto-HSCT within 60 days of enrolment, and had a history of varicella infection or were seropositive for antibodies to varicella zoster virus, or both. Exclusion criteria included a history of herpes zoster within the previous year of enrolment, and intended antiviral prophylaxis for longer than 6 months after transplantation. Participants were randomly assigned according to a central randomisation schedule generated by the trial statistician, to receive either the inactivated-virus vaccine from one of three consistency lots, a high-antigen lot, or placebo, stratified by age (<50 vs ≥50 years) and intended duration of antiviral prophylaxis after transplantation (≤3 months vs >3 to ≤6 months). Participants, investigators, trial staff, and the funder's clinical and laboratory personnel were masked to group assignment. Participants were given four doses of inactivated vaccine or placebo, with the first dose 5–60 days before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 days after transplantation. The primary efficacy endpoint was the incidence of herpes zoster, confirmed by PCR or adjudication by a masked clinical committee, or both, assessed in all participants randomly assigned to the vaccine consistency lot group or placebo group who received at least one dose of vaccine and had auto-HSCT. Safety was assessed in all randomised participants who received at least one dose of vaccine and had follow-up data. A prespecified vaccine efficacy success criterion required the lower bound of the 95% CI be higher than 25% for the relative reduction of the hazard ratio of herpes zoster infection in participants given the vaccine from one of the consistency lots compared with those given placebo. This trial is registered on ClinicalTrials.gov (NCT01229267) and EudraCT (2010–020150–34).
Between Dec 7, 2010, and April 25, 2013, 560 participants were randomly assigned to the vaccine consistency lot group, 106 to the high-antigen lot group, and 564 to the placebo group. 249 (44%) of patients in the vaccine consistency lot group, 35 (33%) in the high-antigen lot group, and 220 (39%) in the placebo group discontinued before study end, mostly because of death or withdrawal. 51 participants were excluded from the primary efficacy endpoint analyses because they did not undergo auto-HSCT or were not vaccinated, or both (22 4% in the vaccine consistency lot group, and 29 5% in the placebo group). Mean follow-up for efficacy was 2·4 years (SD 1·3) in the vaccine consistency lot group and 2·3 years (SD 1·3) in the placebo group. 42 (8%) of 538 participants in the vaccine consistency lot group (32·9 per 1000 person-years) and 113 (21%) of 535 in the placebo group (91·9 per 1000 person-years) had a confirmed case of herpes zoster. The estimated vaccine efficacy was 63·8% (95% CI 48·4–74·6), meeting the pre-specified success criterion. For the combined vaccine groups versus the placebo group, the proportion of patients with serious adverse events (216 33% of 657 vs 181 33% of 554; risk difference 0·2%, 95% CI −5·1 to 5·5) and serious vaccine-related adverse events (five 1% vs five 1%; risk difference 0·1%, −1·4 to 1·1) were similar. Vaccine-related injection-site adverse events occurred more frequently in participants given vaccine than those given placebo (191 29% vs 36 7%; risk difference 22·6%, 95% CI 18·5–26·6; p<0·0001).
This study shows for the first time in a large phase 3 trial that early vaccination of auto-HSCT recipients during the peri-transplant period can be effective for the prevention of an opportunistic infection like herpes zoster and that the vaccine is well tolerated.
Merck & Co., Inc.
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