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BACKGROUND & OBJECTIVES: The primary objective of this observational study was to perform an exhaustive description concerning patients receiving extracorporeal photopheresis (ECP) as second line treatment after steroid resistance for either acute or chronic GVHD following allo-HCT, secondary objectives were to evaluate the efficacy and long-term outcomes. STUDY DESIGN: A total of 106 patients were included, 65 (61%) males and 41 (39%) females with a median age at transplantation of 52 years (range: 20-67). ECP was initiated after transplantation either for acute GVHD [N = 25 (24%), 12 grade III and 13 grade IV] affecting skin alone (N = 5), gut alone (N = 12), gut and liver (N = 8), or chronic GVHD [N = 81 (76%), 15 (14%) limited and 66 (62%) extensive]. RESULTS: Among the 25 patients treated for acute GHVD, 67% were responders and among the 81 patients with chronic GVHD, 78% were responders. Patients with acute GVHD had a median OS of 6 months with a survival probability at 2 years of 35% [95%CI: 14-56]. Patients with chronic GVHD had a median OS of 72 months with a survival probability at 2 years of 68% [95%CI: 56-78]. There was a significant difference in terms of survival for patients responding to ECP compared to non-responders in both acute and chronic GVHD forms. Acute GVHD grade III-IV, negatively impacted on OS (HR=7.77, 95%CI: 1.7-34), p = 0.007 and on disease relapse HR= 5.88, 95%CI: 1.7-20, p = 0.005. CONCLUSION: We demonstrated that ECP is an effective treatment for GVHD in a good proportion of patients with high overall response rate.
Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Fotoferese , Humanos , Fotoferese/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Transplante de Células-Tronco Hematopoéticas/métodos , Idoso , Neoplasias Hematológicas/terapia , Doença Crônica , Transplante Homólogo/métodos , Doença Aguda , Adulto JovemRESUMO
Carbon monoxide (CO)-based tests have precisely measured hemolysis for over 40 years. End-tidal CO was the primary marker in clinical hematology research, followed by carboxyhemoglobin. Quantification of CO reflects heme oxygenases degrading heme in a 1:1 stoichiometric ratio, making CO a direct marker of hemolysis. CO in alveolar air can be quantified using gas chromatography, whose high resolution allows detecting mild and moderate levels of hemolysis. CO can be elevated in active bleeding, resorbing hematoma, and smoking. Clinical acumen and other markers remain necessary to diagnose the cause of hemolysis. CO-based tests constitute an opportunity for bench-to-bedside technology transfer.
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Monóxido de Carbono , Hemólise , Humanos , Monóxido de Carbono/análise , Fumar , Carboxihemoglobina/análise , BiomarcadoresRESUMO
The incidence of acute myeloid leukemia increases with age, and more than half of AML patients are over 60 years old. Treating elderly AML patients presents several challenges and uncertainties, linked partly to disease characteristics and partly to the difficulty of establishing which patients could benefit from the best treatment. Although some elderly fit patients can receive intensive therapy, many of them are not treated and not enrolled in clinical trials. Yet supportive care is associated with significantly lower survival rates compared to intensive therapy or lower intensive therapy. A poorer prognosis in elderly patients is related to age, functional status, and comorbidities, combined with leukemia characteristics. Chronological age is not the best surrogate factor for selecting patients eligible for intensive chemotherapy. Scoring systems-including patient characteristics (ECOG, comorbidities) and disease characteristics (cytogenetics and molecular parameters)-designed to evaluate probabilities of response to treatment, morbidity, and survival may be used to balance the risk-benefit ratio for intensive therapy. A geriatric assessment (GA) to evaluate physical function, comorbidities, nutritional status, cognitive function, and social support could help identify the most vulnerable patients so that they can receive intensive therapy. A GA would also help take the necessary steps to improve tolerance to treatment. Evaluating markers of fitness and quality of life as part of clinical trials should be favored.
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Leucemia Mieloide Aguda/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Comorbidade , Estado Funcional , Avaliação Geriátrica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Prognóstico , Qualidade de VidaAssuntos
Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Seguimentos , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Prognóstico , Análise de Sobrevida , Transplante HomólogoRESUMO
The purpose of this study is to define the optimal dose of oral cyclosporine A (CsA) microemulsion in newborn swine for transplantation studies and to describe its pharmacokinetics and acute renal effects in short-term administration. Thirteen neonatal pigs were randomized into four groups: one control and three groups with CsA administration at 4, 8 and 12 mg/kg/d for 15 days (D). Blood samples were collected on D 0, 2, 4, 9 and 14 to determine the changes of the CsA trough concentrations, the creatinine (Cr) and blood urea nitrogen (BUN) serum concentrations. On D 14, blood samples were collected every hour from 1 h to 10 h after CsA administration to determine the area under the curve (AUC). On D 15, kidneys were removed for histological analysis. We observed a stabilization of CsA trough concentrations from D 4 to D 14. On D 14, in the three treated groups, CsA trough concentrations were 687 ± 7, 1200 ± 77 and 2211 ± 1030 ng/ml, respectively; AUC (0-10 h) were 6721 ± 51 ng·h/ml in group 4 mg/kg/d, 13431 ± 988 ng·h/ml in group 8 mg/kg/d and 28264 ± 9430 ng·h/ml in group 12 mg/kg/d. Cr concentrations were not significantly different among the four groups; but compared to control group, BUN concentrations of the three treated groups increased significantly. CsA was well tolerated; neither acute, severe adverse event nor renal histological abnormality was observed. In conclusion, a 15-d course of oral CsA treatment ranged from 4 to 12 mg/kg/d is safe for newborn pigs, which need much lower CsA dose than adult pigs to reach comparable trough level and AUC. As immunosuppressive therapy in newborn pigs, we recommend a CsA dose of 4 mg/kg/d to achieve a trough blood concentration between 400 and 800 ng/ml.
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Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Tolerância ao Transplante/efeitos dos fármacos , Administração Oral , Animais , Animais Recém-Nascidos , Área Sob a Curva , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Ciclosporina/sangue , Relação Dose-Resposta Imunológica , Feminino , Imunossupressores/sangue , Rim/patologia , Masculino , Distribuição Aleatória , SuínosRESUMO
BACKGROUND: Despite frequent anemia and multiple transfusions in patients undergoing chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia , recommendations for use of erythropoiesis-stimulating agents (ESAs) in these populations are still missing. The primary objective was the effect of ESA administration on patient's quality of life (QoL). Secondary objectives were hemoglobin (Hb) recovery, red blood cell (RBC) transfusions, overall survival, and event-free survival. METHODS: Adult patients with Hb ≤ 11 g/dL after consolidation chemotherapy for acute myeloid leukemia (group 1), or after allo-HSCT for any hematological diseases (group 2), were prospectively included. ESA was administered subcutaneously once per week during a maximum period of 6 months and was stopped when Hb level reached 12 g/dL. A paired-matched analysis using a historical control group was performed for secondary endpoints. Fifty-two patients were included in group 1, and 55 patients were in group 2. RESULTS: For the global population, a significant improvement of QoL was noticed with ESA use; 83% (group 1) and 71% (group 2) of patients achieved an Hb level ≥ 12 g/dL without transfusion requirement. The pair-matched analysis showed a reduction of 4 RBC units per patient in group 1 (P = .0002) and 3 RBC units per patient in group 2 (P = .04). No significant difference in terms of thromboembolic events, overall survival, and event-free survival was observed between ESA and control groups. A RBC transfusion median savings of 1712 per patient was estimated in each group. CONCLUSIONS: ESAs have a clinical and economic benefit on Hb recovery, could improve a patient's QoL, and lead to a significant reduction in number of RBC transfusions with no effect on survival.
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Eritropoetina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/psicologia , Adulto , Idoso , Análise Custo-Benefício , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/economia , Humanos , Leucemia Mieloide Aguda/economia , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Adulto JovemRESUMO
We present results of a phase 3 randomized trial of autografting in chronic lymphocytic leukemia versus observation for responding patients after first- or second-line treatment. The primary objective was to demonstrate that autografting improves the 5-year event-free survival (EFS) from 30% to 50%. There were 223 enrolled patients, 72% men and 28% women, 83% after first and 17% after second-line treatment. Binet stages were progressive A 13%, B 67%, C 20%; at randomization, 59% were in complete remission, and 41% in less than complete remission. Patients were randomized between autografting (n = 112) and observation (n = 111). Median EFS was 24.4 months (range, 16.7-32 months) in the observation group and 51.2 months (39.8-62.5 months) in the autografting group; the 5-year EFS was 24% and 42%, respectively (P < .001). Accordingly, the 5-year relapse incidence was 76% versus 54% (P < .001). Median time to relapse requiring therapy or death was 40 months (25-56 months) in the observation arm and 65 months (59-71 months) after autografting (P = .002). Cox modeling confirmed that autografting significantly improved EFS (hazard ratio 0.44, 95% confidence interval 0.30-0.65; P < .001). At 5 years, the probability of OS was 85.5% and 84.3% for autografting and observation, respectively (P = .77). In chronic lymphocytic leukemia, consolidating autografting reduces the risk of progression by more than 50% but has no effect on overall survival.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B/terapia , Adulto , Idoso , Terapia Combinada , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Transplante Autólogo , Resultado do TratamentoAssuntos
Medula Óssea/patologia , Quimerismo , Doença Enxerto-Hospedeiro/etiologia , Transplante de Órgãos/efeitos adversos , Vísceras/transplante , Evolução Fatal , Feminino , Histocompatibilidade/imunologia , Humanos , Pessoa de Meia-Idade , Transplante de Órgãos/métodos , Rituximab/uso terapêutico , Linfócitos T/imunologia , Doadores de TecidosRESUMO
BACKGROUND: Chimeric antigen receptor T cell therapy (CAR-T) represents a promising and exciting new therapy for hematologic malignancies, where prognosis for relapsed/refractory patients remains poor. Encouraging results from clinical trials have often been tempered by heterogeneity in response to treatment among patients, as well as safety concerns including cytokine release syndrome. The identification of specific patient or treatment-specific factors underlying this heterogeneity may provide the key to the long-term sustainability of this complex and expensive therapy. An individual patient data meta-analysis (IPMDA) may provide potential explanations for the high degree of heterogeneity. Therefore, our objective is to perform a systematic review and IPDMA of CAR-T cell therapy in patients with hematologic malignancies to explore potential effect modifiers of CAR-T cell therapy. METHODS AND ANALYSIS: We will search MEDLINE, Embase, and the Cochrane Central Register of Controlled Clinical Trials. Studies will be screened in duplicate at the abstract level, then at the full-text level by two independent reviewers. We will include any prospective clinical trial of CAR-T cell therapy in patients with hematologic malignancies. Our primary outcome is complete response, while secondary outcomes of interest include overall response, progression-free survival, overall survival, and safety. IPD will be collected from each included trial and, in the case of missing data, corresponding authors/study sponsors will be contacted. Standard aggregate meta-analyses will be performed, followed by the IPD meta-analysis using a one-stage approach. A modified Institute of Health Economics tool will be used to evaluate the risk of bias of included studies. ETHICS AND DISSEMINATION: Identifying characteristics that may act as modifiers of CAR-T cell efficacy is of paramount importance and can help shape future clinical trials in the field. Results from this study will be submitted for publication in a peer-reviewed scientific journal, presented at relevant conferences and shared with relevant stakeholders.
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Neoplasias Hematológicas , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Estudos Prospectivos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/etiologia , Linfócitos T , Revisões Sistemáticas como Assunto , Metanálise como AssuntoRESUMO
Purpose: This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV). Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1. Results: Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%). Conclusions: AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up. Translational Relevance: This systematic review will help to inform and guide future clinical trials.
Assuntos
Degeneração Macular , Degeneração Retiniana , Retinose Pigmentar , Humanos , Degeneração Retiniana/terapia , Dependovirus/genética , Degeneração Macular/tratamento farmacológico , Terapia Genética/efeitos adversosRESUMO
BACKGROUND: t-AML occurs after a primary malignancy treatment and retains a poor prognosis. AIMS: To determine the impact of primary malignancies, therapeutic strategies, and prognostic factors on clinical outcomes of t-AML. RESULTS: A total of 112 adult patients were included in this study. Fifty-Five patients received intensive chemotherapy (IC), 33 non-IC, and 24 best supportive care. At t-AML diagnosis, 42% and 44% of patients presented an unfavorable karyotype and unfavorable 2010 ELN risk profile, respectively. Among treated patients (n = 88), 43 (49%) achieved complete remission: four out of 33 (12%) and 39 out of 55 (71%) in non-IC and IC groups, respectively. With a median follow-up of 5.5 months, the median overall survival (OS) and disease-free survival (DFS) for the whole population were 9 months and 6.3 months, respectively, and for the 88 treated patients 13.5 months and 8.2 months, respectively. Univariate analysis on OS and DFS showed a significant impact of high white blood cells (WBC) and blast counts at diagnosis, unfavorable karyotype and ELN classification. Multivariate analysis showed a negative impact of WBC count at diagnosis and a positive impact of chemotherapy on OS and DFS in the whole population. It also showed a negative impact of previous auto-HCT and high WBC count on OS and DFS and of IC on OS in treated patients which disappeared when we considered only confounding variables (age, previous cancers, marrow blasts, and 2010 ELN classification). In a pair-matched analysis comparing IC treated t-AML with de novo AML, there was no difference of OS and DFS between the two populations. CONCLUSION: We showed, in this study that t-AML patients with unfavorable features represented almost half of the population. Best outcomes obtained in patients receiving IC must be balanced by known confounding variables and should be improved by using new innovative agents and therapeutic strategies.
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Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia Mieloide Aguda , Adulto , Humanos , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Intervalo Livre de Doença , Indução de Remissão , Hospitais , Estudos RetrospectivosAssuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Doadores não Relacionados , Adulto , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Recidiva Local de Neoplasia , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
Different RIC regimens were evaluated prior to allo-HSCT in different hematological malignancies. We conducted this prospective study in adult patients with various hematological malignancies in order to evaluate the toxicity and efficacy of treosulfan-based conditioning, followed by allo-HSCT from 10/10 HLA-identical unrelated donors. Conditioning included treosulfan 12 g/m(2)/day i.v. (day -6 to day -4), fludarabine 30 mg/m(2)/day i.v. (day -6 to day -2), and ATG 2.5 mg/kg/day (day -2 to day -1). PBSC were used as HSC source. We included 56 patients (29 AML, 9 MM, 8 MDS, 6 CLL, 3 ALL, and 1 CML) with a median age of 57 years (18-65.5). Fifty-four (96%) patients engrafted; the cumulative incidence of aGVHD grade ≥II at 3 months reached 31%. The cumulative incidence of cGVHD at 18 months was 34% limited and 8% extensive. The median overall survival (OS) was not reached with a 3-year probability of 52%. The cumulative incidence of relapse at 3 years was 25%, and the cumulative incidence of transplant-related mortality (TRM) at 12 and 24 months was 20% and 23%, respectively. Treosulfan appears to be a good alternative for conditioning of MUD transplant patients with promising results in terms of OS, relapse, and TRM.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/análogos & derivados , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Condicionamento Pré-Transplante/métodos , Doadores não Relacionados , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Bussulfano/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Antígenos HLA/imunologia , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Histocompatibilidade/efeitos dos fármacos , Histocompatibilidade/fisiologia , Teste de Histocompatibilidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo , Adulto JovemRESUMO
BACKGROUND: Resistant starches (RSs) have been advocated as a dietary supplement to address microbiota dysbiosis. They are postulated to act through the production of SCFAs. Their clinical tolerability and effect on SCFA production has not been systematically evaluated. OBJECTIVES: We conducted a systematic review of RS supplementation as an intervention in adults (healthy individuals and persons with medical conditions) participating in randomized controlled trials. The primary outcome was tolerability of RS supplementation, the secondary outcome was SCFA production. METHODS: MEDLINE, Embase, and the Cochrane Central Register were searched. Articles were screened, and data extracted, independently and in duplicate. RESULTS: A total of 39 trials met eligibility criteria, including a total of 2263 patients. Twenty-seven (69%) studies evaluated the impact of RS supplementation in healthy subjects whereas 12 (31%) studies included individuals with an underlying medical condition (e.g., obesity, prediabetes). Type 2 RS was most frequently investigated (29 studies). Of 12 studies performed in subjects with health conditions, 11 reported on tolerability. All studies showed that RS supplementation was tolerated; 9 of these studies used type 2 RS with doses of 20-40 g/d for >4 wk. Of 27 studies performed in healthy subjects, 20 reported on tolerability. In 14 studies, RS supplementation was tolerated, and the majority used type 2 RS with a dose between 20 and 40 g/d. Twenty-one (78%) studies reporting SCFAs used type 2 RS with a dose of 20-40 g/d for 1-4 wk. In 16 of 23 studies (70%), SCFA production was increased, in 7 studies there was no change in SCFA concentration before and after RS supplementation, and in 1 study SCFA concentration decreased. CONCLUSIONS: Available evidence suggests that RS supplementation is tolerated in both healthy subjects and in those with an underlying medical condition. In addition, SCFA production was increased in most of the studies.
Assuntos
Estado Pré-Diabético , Amido Resistente , Adulto , Suplementos Nutricionais , Humanos , Obesidade , AmidoRESUMO
BACKGROUND: Although recommended in patients with acute myeloblastic leukaemia (AML) after induction chemotherapy, real-life use of antifungal prophylaxis (AFP) is different among centres. MATERIALS AND METHODS: This is an ancillary study to a randomized trial on intensive induction chemotherapy in AML patients (ALFA-0702/NCT00932412), where AFP with posaconazole was recommended. IFIs were graded by investigators and by central reviewers according to the revised EORTC definitions. Experts conclusions were compared to the investigators' ones. RESULTS: A total of 677 patients were included. Four AFP strategies were reported: Group-1: no AFP (n = 203, 30%), Group-2: posaconazole (n = 241, 36%), Group-3: posaconazole with other AFP (n = 142, 21%), Group-4: other AFP (n = 91, 13%). Experts graded more IFI than investigators: proven/probable IFI, 9.0% (n = 61) versus 6.2% (n = 42). The cumulative incidence at day60 of probable/proven IFI was 13.9% (Group-1); 7.9% (Group-2); 5.6% (Group-3); and 6.6% (Group-4). IFI onset was 26 (19-31) days after induction in Groups 2-3, versus 16 (9-25) days in Group 1 and 20 (12-24) days in Group 4 (P< .001). After a median follow-up of 27.5 months (0.4-73.4), the mortality rate was 38.3%, with 5.4% attributed to IFI. In multivariate analysis, IFI occurrence was an independent risk of death (HR5.63, 95%-CI 2.62-12.08, P< .001). EORTC recommendations were applied in only 57% of patients. In patients without IFI, the rate of AML complete remission was higher. CONCLUSIONS: In AML patients, AFP delayed the onset of IFI in addition of decreasing their rate. The frequent misidentification of IFI impacts their appropriate management according to recommendations. hematological remission was more frequent in patients without IFI.
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Leucemia Mieloide Aguda , Micoses , Doença Aguda , Antifúngicos/uso terapêutico , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Micoses/etiologia , Micoses/prevenção & controle , alfa-Fetoproteínas/uso terapêuticoAssuntos
Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Condicionamento Pré-Transplante , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Feminino , Seguimentos , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sociedades Médicas , Doadores não RelacionadosRESUMO
BACKGROUND: The study objectives were: 1) to report on invasive aspergillosis patients in a hematology department; and 2) to estimate its incidence according to the hematologic diagnosis. DESIGN AND METHODS: A prospective survey of invasive aspergillosis cases was undertaken between January 2004 and December 2009 in the hematology department of a university hospital. Meetings with clinicians, mycologists and infection control practitioners were organized monthly to confirm suspected aspergillosis cases. Demographic characteristics, clinical and complementary examination results were recorded prospectively. Information on hospitalization was extracted from administrative databases. Invasive aspergillosis diagnosis followed the European Organization for Research and Treatment of Cancer criteria, and proven and probable IA cases were retained. A descriptive analysis was conducted with temporal trends of invasive aspergillosis incidence assessed by adjusted Poisson regression. RESULTS: Overall, 4,073 hospitalized patients (78,360 patient-days) were included in the study. In total, 127 (3.1%) patients presented invasive aspergillosis. The overall incidence was 1.6 per 1,000 patient-days (95% confidence interval: 1.4, 1.9) with a decrease of 16% per year (-1%, -28%). The incidence was 1.9 per 1,000 patient-days (1.5, 2.3) in acute myeloid leukemia patients with a decrease of 20% per year (-6%, -36%). Serum Aspergillus antigen was detected in 89 (71%) patients; 29 (23%) had positive cultures, and 118 (93%), abnormal lung CT scans. One-month mortality was 13%; 3-month mortality was 42%. Mortality tended to decrease between 2004 and 2009. CONCLUSIONS: Invasive aspergillosis incidence and mortality declined between 2004 and 2009. Knowledge of invasive aspergillosis characteristics and its clinical course should help to improve the management of these patients with severe disease.
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Antígenos de Fungos/sangue , Aspergilose/sangue , Aspergilose/epidemiologia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/epidemiologia , Adulto , Aspergilose/diagnóstico por imagem , Coleta de Dados , Feminino , Neoplasias Hematológicas/diagnóstico por imagem , Neoplasias Hematológicas/microbiologia , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Índice de Gravidade de DoençaAssuntos
Antineoplásicos/uso terapêutico , Doença da Artéria Coronariana/etiologia , Hiper-Homocisteinemia/tratamento farmacológico , Mesilato de Imatinib/uso terapêutico , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Pirimidinas/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , HDL-Colesterol/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/prevenção & controle , Esquema de Medicação , Feminino , Homocisteína/sangue , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/patologia , Leucemia Mieloide de Fase Crônica/sangue , Leucemia Mieloide de Fase Crônica/complicações , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirimidinas/administração & dosagem , Estudos Retrospectivos , Triglicerídeos/sangueRESUMO
Invasive aspergillosis (IA) is an important cause of morbidity and mortality in neutropenic patients with hematological malignancies. To investigate the immediate and mid-term benefits of posaconazole prophylaxis in AML patients undergoing first induction chemotherapy and to study the infection risk factors, we prospectively studied the IA incidence in these patients at our hospital between years 2007 and 2008; then we compared them to a matched control group without prophylaxis. There were 55 and 66 patients in each group respectively. At day 32 post-induction, two probable cases (3.6%) were scored in the prophylaxis group compared to 8 cases (12.1%) in the control group (4 possible and 4 probable). At day 100, it reached 7.27% and 15.5% respectively. Kaplan-Meier analysis at day 100 showed lower mortality rate in the prophylaxis group compared to the control group [3.64% (n = 2, none due to IA) and 10.61% (n = 7, four due to IA) respectively, P = 0.002]. Multivariate analysis showed age and lack of response to induction as independent infection risk factors. Posaconazole prophylaxis resulted in lower incidence of IA and significantly improved survival. Patient's age and response to induction treatment are two independent infection risk factors, and need more attention during future clinical trials linked to antifungal prophylaxis.
Assuntos
Antifúngicos/administração & dosagem , Aspergilose/epidemiologia , Aspergilose/prevenção & controle , Quimioprevenção/métodos , Leucemia Mieloide Aguda/complicações , Triazóis/administração & dosagem , Adulto , Idoso , Aspergilose/mortalidade , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
BACKGROUND: In Canadian adults, follicular lymphoma (FL) is the most common subtype of non-Hodgkin lymphomas. Approximately 20% of patients with FL experience progression of disease within 2 years of first-line chemoimmunotherapy. Those patients have an expected overall survival of less than 5 years. The optimal second-line treatment for these high-risk patients is unclear. PATIENTS AND METHODS: We analyzed data from the Blood and Bone Marrow Transplantation Center at Ottawa Hospital to determine whether autologous stem-cell transplantation as up-front therapy for first relapse can improve outcomes in this high-risk FL subgroup. We identified 17 patients who underwent up-front autologous stem-cell transplantation between February 2012 and February 2019. RESULTS: The disease of all patients had relapsed within 24 months after receipt of their first rituximab-based chemotherapy. Overall survival at 2 and 5 years was 86.2% (95% confidence interval [CI], 55-96) and 71.8% (95% CI, 31-91), respectively. The progression-free survival at 2 and 5 years was 62.6% (95% CI, 35-81) and 53.6% (95% CI, 25-75), respectively. CONCLUSION: Overall survival is improved when receiving autologous hematopoietic stem-cell transplantation as up-front therapy at first relapse in transplant-eligible FL whose disease relapses within 24 months of first-line therapy. Data from our single center look promising, but the data need to be replicated with a larger sample size.