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The European LeukemiaNet (ELN) genetic risk classifications were developed based on data from younger adults receiving intensive chemotherapy. Emerging analyses from patients receiving less-intensive therapies prompted a proposal for an ELN genetic risk classification specifically for this patient population.
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We investigated whether secondary versus de novo acute myeloid leukaemia (AML) would be associated with poor outcomes in adult acute AML patients in first complete remission (CR1) receiving unrelated cord blood transplantation (CBT). This is a retrospective study from the acute leukaemia working party of the European Society for Blood and Marrow Transplantation. Inclusion criteria included adult at first allogeneic haematopoietic cell transplantation between 2000 and 2021, unrelated single or double unit CBT, AML in CR1, no ex vivo T-cell depletion and no post-transplant cyclophosphamide. The primary end-point of the study was leukaemia-free survival (LFS). A total of 879 patients with de novo (n = 696) or secondary (n = 183) AML met the inclusion criteria. In multivariable analyses, sAML patients had non-significantly different LFS (HR = 0.98, p = 0.86), overall survival (HR = 1.07, p = 0.58), relapse incidence (HR = 0.74, p = 0.09) and non-relapse mortality (HR = 1.26, p = 0.13) than those with de novo AML. Our results demonstrate non-significantly different LFS following CBT in adult patients with secondary versus de novo AML.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Segunda Neoplasia Primária , Adulto , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Leucemia Mieloide Aguda/complicações , Transplante de Células-Tronco Hematopoéticas/métodos , Segunda Neoplasia Primária/etiologia , Condicionamento Pré-Transplante/métodos , Doença Enxerto-Hospedeiro/etiologia , Receptores de Complemento 3bRESUMO
The 2010 and 2017 editions of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults are widely recognized among physicians and investigators. There have been major advances in our understanding of AML, including new knowledge about the molecular pathogenesis of AML, leading to an update of the disease classification, technological progress in genomic diagnostics and assessment of measurable residual disease, and the successful development of new therapeutic agents, such as FLT3, IDH1, IDH2, and BCL2 inhibitors. These advances have prompted this update that includes a revised ELN genetic risk classification, revised response criteria, and treatment recommendations.
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Antineoplásicos , Leucemia Mieloide Aguda , Adulto , Antineoplásicos/uso terapêutico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamento farmacológico , Nucleofosmina , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/genéticaRESUMO
The phase 3 ADMIRAL (NCT02421939; Study ID: 2215-CL-0301) trial showed superior overall survival in patients with relapsed/refractory FLT3-mutation-positive acute myeloid leukemia (AML) randomized 2:1 to receive the oral FMS-like tyrosine kinase 3 inhibitor gilteritinib vs those randomized to receive salvage chemotherapy (SC). Here we provide a follow-up of the ADMIRAL trial 2 years after the primary analysis to clarify the long-term treatment effects and safety of gilteritinib in these patients with AML. At the time of this analysis, the median survival follow-up was 37.1 months, with deaths in 203 of 247 and 97 of 124 patients in the gilteritinib and SC arms, respectively; 16 gilteritinib-treated patients remained on treatment. The median overall survival for the gilteritinib and SC arms was 9.3 and 5.6 months, respectively (hazard ratio, 0.665; 95% confidence interval [CI], 0.518, 0.853; two-sided P = .0013); 2-year estimated survival rates were 20.6% (95% CI, 15.8, 26.0) and 14.2% (95% CI, 8.3, 21.6). The gilteritinib-arm 2-year cumulative incidence of relapse after composite complete remission was 75.7%, with few relapses occurring after 18 months. Overall, 49 of 247 patients in the gilteritinib arm and 14 of 124 patients in the SC arm were alive for ≥2 years. Twenty-six gilteritinib-treated patients remained alive for ≥2 years without relapse; 18 of these patients underwent transplantation (hematopoietic stem cell transplantation [HSCT]) and 16 restarted gilteritinib as post-HSCT maintenance therapy. The most common adverse events of interest during years 1 and 2 of gilteritinib therapy were increased liver transaminase levels; adverse event incidence decreased in year 2. Thus, continued and post-HSCT gilteritinib maintenance treatment sustained remission with a stable safety profile. These findings confirm that prolonged gilteritinib therapy is safe and is associated with superior survival vs SC. This trial was registered at www.clinicaltrials.gov as #NCT02421939.
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Compostos de Anilina , Leucemia Mieloide Aguda , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Seguimentos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Pirazinas , Recidiva , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
The current study includes all consecutive patients (N = 484) who received a reduced-intensity conditioning regimen (RIC) allogeneic hematopoietic stem cell transplantation in our center from 1999 to 2020. Conditioning regimens were based on fludarabine with melphalan or busulfan, with low-dose thiotepa and pharmacological GVHD prophylaxis consisted of cyclosporine A (CsA)-methotrexate (MTX)/mofetil (MMF) (n = 271), tacrolimus-sirolimus (n = 145), and post-transplantation cyclophosphamide (PTCy)-tacrolimus (n = 68). The median time of overall follow-up in survivors was 8 years (1-22 years) and was at least 3 years in all three GVHD prophylaxis groups. Thirty-three percent had a high or very high disease risk index, 56% ≥ 4 European bone marrow transplantation risk, and 65% ≥ 3 hematopoietic stem cell transplantation comorbidity index score-age score. Neutrophil and platelet engraftment was longer for PTCy-tacro (p 0.0001). Cumulative incidence of grade III-IV aGVHD was 17% at 200 days, and that of moderate-severe cGvHD was 36% at 8 years. GVHD prophylaxis was the only prognostic factor in the multivariable analyses for the development of aGVHD and moderate-severe cGVHD (p 0.0001). NRM and relapse incidences were 29% and 30% at 8 years, while OS and PFS rates were 43% and 39% at 8 years. At 3 years, OS was highest in the PTCy-tacro group (68%) than in the tacro-siro (61%) and CsA-MTX/MMF (49%) cohorts (p < 0.01). In the three groups, respectively, the 200-day incidence of grade III-IV aGvHD (6% vs. 12% vs. 23%) and 3-year moderate-severe cGVHD (8% vs. 40% vs. 38%) were lower in the PTCy cohort. These better outcomes were confirmed in multivariable analyses. Based on our recent results, the PTCy could be considered as a real GvHD prophylaxis in the RIC setting due to improve best 3-year GvHD and survival outcomes.
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Doença Enxerto-Hospedeiro , Doenças Hematológicas , Transplante de Células-Tronco Hematopoéticas , Humanos , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doenças Hematológicas/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Metotrexato/uso terapêutico , Tacrolimo/uso terapêutico , Condicionamento Pré-Transplante/métodosRESUMO
Osteoporosis is characterised by the loss of bone density resulting in an increased risk of fragility fractures. The clinical gold standard for diagnosing osteoporosis is based on the areal bone mineral density (aBMD) used as a surrogate for bone strength, in combination with clinical risk factors. Finite element (FE) analyses based on quantitative computed tomography (QCT) have been shown to estimate bone strength better than aBMD. However, their application in the osteoporosis clinics is limited due to exposure of patients to increased X-rays radiation dose. Statistical modelling methods (3D-DXA) enabling the estimation of 3D femur shape and volumetric bone density from dual energy X-ray absorptiometry (DXA) scan have been shown to improve osteoporosis management. The current study used 3D-DXA based FE analyses to estimate femur strength from the routine clinical DXA scans and compared its results against 151 QCT based FE analyses, in a clinical cohort of 157 subjects. The linear regression between the femur strength predicted by QCT-FE and 3D-DXA-FE models correlated highly (coefficient of determination R2â¯=â¯0.86) with a root mean square error (RMSE) of 397 N. In conclusion, the current study presented a 3D-DXA-FE modelling tool providing accurate femur strength estimates noninvasively, compared to QCT-FE models.
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Absorciometria de Fóton , Densidade Óssea , Fêmur , Análise de Elementos Finitos , Imageamento Tridimensional , Tomografia Computadorizada por Raios X , Humanos , Fêmur/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Osteoporose/diagnóstico por imagem , Osteoporose/fisiopatologia , Idoso de 80 Anos ou maisRESUMO
Renal involvement is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The present study included patients with recently diagnosed Class III and Class IV lupus nephritis (LN) treated by Rheumatology who, upon the detection of alterations in their kidney function, were referred to Nephrology for the joint management of both medical specialties. The purpose of this study was to compare the plasma expression of Toll-Like Receptor 7 (TLR7) and TLR9 in healthy control (HC) subjects and newly diagnosed Class III and Class IV LN patients with 12-month follow-ups. The plasma expression of TLR7 and TLR9 proteins was determined by the ELISA method. A significant increase in the expression of TLR7 protein was found in Class III LN in the basal determination compared to the expression in the HC (p = 0.002) and at 12 months of follow-up (p = 0.03) vs. HC. The expression of TLR9 showed a behavior opposite to that of TLR7. TLR9 showed decreased protein expression in LN Class III patients' baseline and final measurements. The result was similar in the basal and final determinations of LN Class IV compared to the expression in HC. A significant decrease in SLEDAI -2K was observed at 12 months of follow-up in patients in Class III (p = 0.01) and Class IV (p = 0.0001) of LN. Complement C3 levels improved significantly at 12-month follow-up in Class IV patients (p = 0.0001). Complement C4 levels decreased significantly at 12-month follow-up in LN Class III compared to baseline (p = 0.01). Anti-DNA antibodies decreased significantly at 12 months of follow-up in Class IV LN (p = 0.01). A significant increase in proteinuria was found at 12 months of follow-up in Class III LN, compared to the baseline determination (p = 0.02). In LN Class IV, proteinuria decreased at 12 months of follow-up compared to baseline (p = 0.0001). Albuminuria decreased at 12 months of follow-up in LN Class IV (p = 0.006). Class IV LN, albuminuria also decreased at 12 months of follow-up (p = 0.009). Hematuria persisted in all patients and the glomerular filtration rate did not change. Three Class IV patients died before 12 months of follow-up from various causes. In conclusion, although the rheumatologic data appeared to improve, the renal function data remained inconsistent. Decreased expression of TLR9 and increased expression of TLR7 could be useful in the early diagnosis of Class III and Class IV LN is correct.
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Nefrite Lúpica , Receptor 7 Toll-Like , Receptor Toll-Like 9 , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/sangue , Nefrite Lúpica/metabolismo , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/genética , Receptor Toll-Like 9/metabolismo , Feminino , Adulto , Masculino , Seguimentos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: Autologous stem cell transplant (ASCT) is a widely used therapy for lymphoma patients and can nowadays be performed on an outpatient basis. This study aimed to describe transfusion support in lymphoma patients undergoing ASCT and identify increased or prolonged transfusion requirement predictors. MATERIALS AND METHODS: A retrospective study of all consecutive lymphoma patients undergoing ASCT between 2010 and 2020. RESULTS: Out of 226 patients, 145 (64%) received red blood cell (RBC) transfusions, whereas all 226 (100%) required platelet transfusion (PT). Transfusions between Day +1 and +30 were higher in patients over 60 (2 [1-4] vs. 2 [0-2] RBC; p = 0.001 and 4 [2-8] vs. 3 [2-4] PT; p < 0.001); patients with pre-transplant anaemia (4 [2.5-6] vs. 2 [0-2] RBC; p < 0.001 and 5 [3-9] vs. 3 [2-4] PT; p = 0.001); pre-transplant thrombocytopenia (2 [1-4] vs. 2 [0-2] RBC; p < 0.001 and 4 [3-8.5] vs. 2 [1-3] PT; p < 0.001) or CD34+ cell dose <4 × 106 /kg (2 [0-4] vs. 2 [0-2] RBC; p = 0.024 and 4 [2-6] vs. 2 [1-3.5] PT; p < 0.001). RBC transfusion independence was reached later in patients receiving carmustine, cytarabine, etoposide and melphalan (BEAM) (hazard ratio [HR] 1.6; confidence interval [CI] 1.1-2.3) and those requiring RBC before infusion and/or with pre-transplant anaemia (HR 2.2; CI 1.4-3.4). Age above 60 (HR 1.4; CI 1.0-1.9), BEAM conditioning (HR 1.4; CI 1.0-2.0) and pre-transplant thrombocytopenia and/or requiring PT before infusion (HR 1.8; CI 1.4-2.5) entailed longer time until PT independence. CONCLUSION: These four factors (age ≥60 years; BEAM conditioning, CD34+ dose <4 × 106 /kg and pre-transplant cytopenia and/or Day -10 to 0 transfusion) allowed dividing patients into three groups with significant differences between them regarding the time until transfusion independence.
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Anemia , Transplante de Células-Tronco Hematopoéticas , Linfoma , Trombocitopenia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma/terapia , Linfoma/etiologia , Transplante de Células-Tronco , Trombocitopenia/etiologia , Anemia/terapia , Anemia/etiologiaRESUMO
OBJECTIVES: High-dose total body irradiation (TBI) is considered a cornerstone of myeloablative conditioning for allogeneic stem cell transplantation (allo-SCT). We retrospectively compared the main outcomes of an HLA matched or 1-allele mismatched related or unrelated allo-SCT in adult patients affected by acute leukemia (AL) or myelodysplastic syndromes (MDS). METHODS: Fifty-nine patients received cyclophosphamide (Cy)-TBI (13.5 Gy) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin-inhibitor plus methrotrexate (CyTBI group) and 28 patients received fludarabine-TBI (8.8-13.5 Gy) and GVHD prophylaxis with PTCy and tacrolimus (FluTBI-PTCy group). RESULTS: Median follow-up for survivors was 82 and 22 months. The 12-month probability of overall survival and progression-free survival were similar (p = .18, p = .7). The incidence of Grades 2-4 and 3-4 acute GVHD, and the incidence of moderate-to-severe chronic GVHD were higher in the CyTBI group (p = .02, p < .01and p = .03). Nonrelapse mortality (NRM) at 12 months posttransplant was higher in the CyTBI group (p = 0.05), while the incidence of relapse was similar in both groups (p = 0.7). The number of GVHD-free and relapse-free patients without systemic immunosuppression (GRFS) at 1-year posttransplant was higher in the FluTBI-PTCy group (p = 0.01). CONCLUSIONS: The study confirms the safety and efficacy of a novel FluTBI-PTCy platform with reduced incidence of severe acute and chronic GVHD, and early improvement of NRM.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adulto , Humanos , Estudos Retrospectivos , Irradiação Corporal Total , Ciclofosfamida/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mieloide Aguda/tratamento farmacológico , Recidiva , Condicionamento Pré-TransplanteRESUMO
End-stage renal disease (ESRD) progression is closely related to oxidative stress (OS). The study objective was to determine the oxidant and antioxidant status in peritoneal dialysis (PD) patients with type 2 diabetes mellitus (DM). An analytical cross-sectional study from the PD program was carried out with 62 patients, 22 with and 40 without DM. Lipoperoxides (LPO) levels in patients with DM, 3.74 ± 1.09 mM/L, and without DM, 3.87 ± 0.84 mM/L were found to increase compared to healthy controls (HC) 3.05 ± 0.58 mM/L (p = 0.006). The levels of the oxidative DNA damage marker (8-OH-dG) were found to be significantly increased in patients with DM, 1.71 ng/mL (0.19-71.92) and without DM, 1.05 ng/mL (0.16-68.80) front to 0.15 ng/mL (0.15-0.1624) of HC (p = 0.001). The antioxidant enzyme superoxide dismutase (SOD) activity was found to be significantly increased in patients with DM, 0.37 ± 0.15 U/mL, and without DM, 0.37 ± 0.17 compared to HC, 0.23 ± 0.05 U/mL (p = 0.038). The activity of the enzyme glutathione peroxidase (GPx) showed a significant increase (p < 0.001) in patients with DM, 3.56 ± 2.18 nmol/min/mL, and without DM, 3.28 ± 1.46 nmol/min/mL, contrary to the activity obtained in HC, 1.55 ± 0.34 nmol/min/mL. In conclusion, we found an imbalance of oxidative status in patients undergoing PD with and without DM through the significant increase in LPO oxidants and the marker of oxidative damage in DNA. The activity of the antioxidant enzymes SOD and GPx were significantly increased in patients with and without DM undergoing PD, possibly in an attempt to compensate for the deregulation of oxidants. Antioxidant enzymes could be promising therapeutic strategies as a complement to the management of chronic kidney diseases.
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Diabetes Mellitus Tipo 2 , Diálise Peritoneal , Humanos , Antioxidantes/metabolismo , Estudos Transversais , Superóxido Dismutase/metabolismo , Estresse Oxidativo , Peróxidos Lipídicos , Glutationa Peroxidase/metabolismo , OxidantesRESUMO
Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immune-pathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the roles of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing roles of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.
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Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/metabolismo , Receptor Toll-Like 9/metabolismo , Receptor 7 Toll-Like/genética , Imunidade Inata , OxirreduçãoRESUMO
Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (≥0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 NPM1/FLT3-ITD genotypes differed significantly with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after 1 or 2 induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly among ELN risk groups, with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate-, and adverse-risk groups, respectively (P < .001). A multivariate Cox model for OS using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.
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Duplicação Gênica , Predisposição Genética para Doença , Leucemia Mieloide Aguda/genética , Proteínas Nucleares/genética , Sequências de Repetição em Tandem/genética , Tirosina Quinase 3 Semelhante a fms/genética , Europa (Continente) , Feminino , Genótipo , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nucleofosmina , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Resultado do TratamentoRESUMO
Acute myeloid leukemia (AML) is a complex disease, and its treatment needs to be adjusted to the risk, which is conferred by cytogenetics and molecular markers. Cytarabine is the main drug to treat AML, and it has been suggested that the genotype of cytarabine metabolizing enzymes may have a prognostic relevance in AML. Here we report the association between the 5'-nucleotidase, cytosolic II (NT5C2) rs10883841, cytidine deaminase (CDA) rs2072671 and rs532545 genotypes and the clinical outcome of 477 intermediate-risk cytogenetic AML patients receiving cytarabine-based chemotherapy. Patients younger than 50 years old with the NT5C2 rs10883841 AA genotype had lower overall survival (OS) (p: .003; HR 2.16, 95% CI 1.29-3.61) and lower disease-free survival (DFS) (p: .002; HR 2.45, 95% CI 1.41-4.27), associated to a higher relapse incidence (p: .010; HR 2.23, 95% CI 1.21-4.12). Interestingly, subgroup analysis showed that the negative effect of the NT5C2 rs10883841 AA genotype was detected in all subgroups except in patients with nucleophosmin mutation without high ratio FLT-3 internal tandem duplication. CDA polymorphisms were associated with the complete remission rate after induction chemotherapy, without influencing OS. Further studies are warranted to determine whether this pharmacogenomic approach may be helpful to individualize AML treatment.
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5'-Nucleotidase , Leucemia Mieloide Aguda , Humanos , Pessoa de Meia-Idade , 5'-Nucleotidase/genética , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Análise Citogenética , Genótipo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Prognóstico , Indução de Remissão , Citidina Desaminase/genéticaRESUMO
PURPOSE: This study aims to describe the incidence and severity of adverse events (AEs) following the mRNA-1273 SARS-CoV-2 vaccine and explore the risk perception of COVID-19 in allogeneic hematopoietic stem cell transplant (HCT) recipients. METHODS: We performed a single-center prospective study including recently transplanted (< 2 years post-infusion) allogeneic HCT recipients. AEs were assessed through phone calls and graded from 0 to 4, while COVID-19 risk perception was measured using the Brief Illness Perception Questionnaire (BIP-Q5). RESULTS: Fifty-four HCT recipients were evaluated. Incidence and grades of AE (94.4% and 85.2% after the first and second dose, respectively) were similar to those described in the general population. The most common AE was pain at the site of injection. Three patients (5.6%) developed a grade ≥ 3 AE. Vaccine-related cytopenias and graft-versus-host disease flares were not observed. Female sex (OR 3.94, 95% CI 1.14-13.58, p = 0.03) and time since HCT (per month since HCT: OR 1.09, 95% CI 1.01-1.18, p = 0.04) were associated with the occurrence of any AE. The patients' risk perception level of COVID-19 decreased over time (p < 0.05). CONCLUSION: Our study confirms that the mRNA-1273 SARS-CoV-2 vaccine is safe in recent HCT recipients and suggests that the perceived risk of COVID-19 decreases over time.
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Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Transplante de Células-Tronco Hematopoéticas , Feminino , Humanos , Vacina de mRNA-1273 contra 2019-nCoV/efeitos adversos , Vacina de mRNA-1273 contra 2019-nCoV/uso terapêutico , COVID-19/prevenção & controle , Estudos Prospectivos , SARS-CoV-2 , Transplante Homólogo , Conhecimentos, Atitudes e Prática em Saúde , Inquéritos e QuestionáriosRESUMO
Background: Acute kidney injury (AKI) is associated with poor outcomes in patients infected with SARS-CoV-2. Sepsis, direct injury to kidney cells by the virus, and severe systemic inflammation are mechanisms implicated in its development. We investigated the association between inflammatory markers (C-reactive protein, procalcitonin, D-dimer, lactate dehydrogenase, and ferritin) in patients infected with SARS-CoV-2 and the development of AKI. Methods: A prospective cohort study performed at the Civil Hospital (Dr. Juan I. Menchaca) Guadalajara, Mexico, included patients aged >18 years with a diagnosis of SARS-CoV-2 pneumonia confirmed by RT-PCR and who did or did not present with AKI (KDIGO) while hospitalized. Biomarkers of inflammation were recorded, and kidney function was estimated using the CKD-EPI formula. Results: 291 patients were included (68% males; average age, 57 years). The incidence of AKI was 40.5% (118 patients); 21% developed stage 1 AKI, 6% developed stage 2 AKI, and 14% developed stage 3 AKI. The development of AKI was associated with higher phosphate (p = 0.002) (RR 1.39, CI 95% 1.13-1.72), high procalcitonin levels at hospital admission (p = 0.005) (RR 2.09, CI 95% 1.26-3.50), and high APACHE scores (p = 0.011) (RR 2.0, CI 95% 1.17-3.40). The survival analysis free of AKI according to procalcitonin levels and APACHE scores demonstrated a lower survival in patients with procalcitonin >0.5 ng/ml (p = 0.001) and APACHE >15 points (p = 0.004). Conclusions: Phosphate, high procalcitonin levels, and APACHE levels >15 were predictors of AKI development in patients hospitalized with COVID-19.
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Injúria Renal Aguda , COVID-19 , Sepse , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , APACHE , SARS-CoV-2 , Pró-Calcitonina , Estudos Prospectivos , Proteína C-Reativa , COVID-19/complicações , COVID-19/diagnóstico , Estudos Retrospectivos , Injúria Renal Aguda/diagnóstico , Biomarcadores , Ferritinas , Fosfatos , Lactato Desidrogenases , Fatores de RiscoRESUMO
Early Chronic Kidney Disease (CKD) is a condition that tends to progress to End-Stage Kidney Disease (ESKD). Early diagnosis of kidney disease in the early stages can reduce complications. Alterations in renal function represent a complication of diabetes mellitus (DM). The mechanisms underlying the progression of CKD in diabetes could be associated with oxidative and inflammatory processes. This study aimed to evaluate the state of inflammation and oxidative stress (OS) on the progression of CKD in the early stages in patients with and without type 2 diabetes mellitus (T2DM). An analytical cross-sectional study was carried out in patients with CKD in early stages (1, 2, 3) with and without T2DM. The ELISA method determined the expression of pro-inflammatory cytokines IL-6 and TNF-α as well as lipoperoxides (LPO), nitric oxide (NO), and superoxide dismutase activity (SOD). Colorimetric methods determined glutathione peroxidase (GPx) and total antioxidant capacity (TAC). Patients with CKD and T2DM had significantly decreased antioxidant defenses for SOD (p < 0.01), GPx (p < 0.01), and TAC (p < 0.01) compared to patients without T2DM. Consequently, patients with T2DM had higher concentrations of oxidant markers, NO (p < 0.01), inflammation markers, IL-6 (p < 0.01), and TNF-α than patients without T2DM. CKD stages were not related to oxidative, antioxidant, and inflammatory marker outcomes in T2DM patients. Patients without T2DM presented an increase in SOD (p = 0.04) and a decrease in NO (p < 0.01) when the stage of CKD increased. In conclusion, patients with T2DM present higher levels of oxidative and inflammatory markers accompanied by a decrease in antioxidant defense. However, these oxidative status markers were associated with CKD stage progression in patients without T2DM. Thus, NO and SOD markers could help detect the early stages of CKD in patients who have not yet developed metabolic comorbidities such as T2DM.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-6/metabolismo , Peróxidos Lipídicos , Óxido Nítrico , Oxidantes , Estresse Oxidativo , Insuficiência Renal Crônica/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The use of myeloablative conditioning (MAC) in umbilical cord blood transplantation (UCBT) has been associated with high nonrelapse mortality (NRM) in patients aged >40 years, especially those having a high HLA disparity, thus limiting wider applications. We hypothesized that the NRM advantage of reduced-intensity conditioning (RIC) and higher graft-versus-leukemia effect associated with greater HLA disparities would expand its use for patients (aged 40 to 60 years) without compromising efficacy and compared outcomes between RIC and MAC regimens. In total, 288 patients aged 40 to 60 years, with de novo acute myeloid leukemia, receiving UCBT with at least 2 HLA mismatches with RIC (n = 166) or MAC (n = 122) regimens were included. As compared to RIC, the MAC cohort included relatively younger patients, having received more single UCBT, with lower total nucleated cell counts and more in vivo T cell depletion. Median time to neutrophil engraftment, infections (bacterial, viral, and fungal), and grade II to IV acute and chronic graft-versus-host disease were similar in both groups. In the multivariate analysis, overall survival (hazard ratio [HR], 0.98; P = .9), NRM (HR, 0.68; P = .2), and relapse (HR, 1.24; P = .5) were not different between RIC and MAC. Refractory disease was associated with worse survival. Outcomes of UBCT for patients aged 40 to 60 years having ≥2 HLA mismatches are comparable after the RIC or MAC regimen.
Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos , Condicionamento Pré-TransplanteRESUMO
Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a poor-risk entity, commonly associated with FLT3-ITD (internal tandem duplication). Allogeneic stem-cell tranplantation (allo-SCT) is recommended, although studies analysing the outcome of allo-SCT in this setting are lacking. We selected 195 patients with t(6;9) AML, who received a first allo-SCT between 2000 and 2016 from the EBMT (European Society for Blood and Marrow Transplantation) registry. Disease status at time of allo-SCT was the strongest independent prognostic factor, with a two-year leukaemia-free survival and relapse incidence of 57% and 19% in patients in CR1 (first complete remission), 34% and 33% in CR2 (second complete remission), and 24% and 49% in patients not in remission, respectively (P < 0·001). This study, which represents the largest one available in t(6;9) AML, supports the recommendation to submit these patients to allo-SCT in CR1.
Assuntos
Proteínas Cromossômicas não Histona/genética , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 9/genética , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Leucemia Mieloide Aguda/terapia , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Oncogênicas/genética , Transplante de Células-Tronco de Sangue Periférico , Proteínas de Ligação a Poli-ADP-Ribose/genética , Translocação Genética , Adulto , Aloenxertos , Cromossomos Humanos Par 6/ultraestrutura , Cromossomos Humanos Par 9/ultraestrutura , Intervalo Livre de Doença , Feminino , Duplicação Gênica , Doença Enxerto-Hospedeiro/etiologia , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Indução de Remissão , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
In the European LeukemiaNet favourable risk category, allogeneic haematopoietic stem cell transplantation (alloSCT) is not indicated in first complete remission for patients with acute myeloid leukaemia (AML) with NPM1 mutations (ELNfav NPM1 AML), although a proportion of these patients will relapse. Given the prognostic importance of measurable residual disease (MRD), CETLAM-12 considered a pre-emptive intervention in patients with molecular failure (MF). We analyzed 110 ELNfav NPM1 AML patients achieving complete remission (CR) after induction chemotherapy. Two-year cumulative incidence of relapse (CIR), overall survival (OS) and leukaemia-free survival (LFS) were 17%, 81·5% and 82%, respectively. Forty-six patients required additional therapy for MF (n = 33) or haematological relapse (HemR; n = 13), resulting in a molecular LFS (molLFS) and a cumulative incidence of MF at two years of 61% and 38% respectively. Two-year OS for these 46 patients was 66%, with a different outcome between patients with MF (86%) and HemR (42%) (P = 0·002). Quantitative NPM1 detection at different timepoints was predictive of molLFS; an MRD ratio (NPM1mut/ABL1 × 100) cut-off of 0·05 after first consolidation identified two cohorts with a two-year molLFS of 77% and 40% for patients below and above 0·05, respectively. In conclusion, MRD-based pre-emptive intervention resulted in a favourable outcome for ELNfav NPM1 AML patients.
Assuntos
Quimioterapia de Indução , Leucemia Mieloide Aguda , Mutação , Proteínas de Neoplasias/genética , Proteínas Nucleares/genética , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Nucleofosmina , Taxa de SobrevidaRESUMO
BACKGROUND: Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin - an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation - to standard chemotherapy would prolong overall survival in this population. METHODS: We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo. Randomization was stratified according to subtype of FLT3 mutation: point mutation in the tyrosine kinase domain (TKD) or internal tandem duplication (ITD) mutation with either a high ratio (>0.7) or a low ratio (0.05 to 0.7) of mutant to wild-type alleles (ITD [high] and ITD [low], respectively). Allogeneic transplantation was allowed. The primary end point was overall survival. RESULTS: A total of 717 patients underwent randomization; 360 were assigned to the midostaurin group, and 357 to the placebo group. The FLT3 subtype was ITD (high) in 214 patients, ITD (low) in 341 patients, and TKD in 162 patients. The treatment groups were well balanced with respect to age, race, FLT3 subtype, cytogenetic risk, and blood counts but not with respect to sex (51.7% in the midostaurin group vs. 59.4% in the placebo group were women, P=0.04). Overall survival was significantly longer in the midostaurin group than in the placebo group (hazard ratio for death, 0.78; one-sided P=0.009), as was event-free survival (hazard ratio for event or death, 0.78; one-sided P=0.002). In both the primary analysis and an analysis in which data for patients who underwent transplantation were censored, the benefit of midostaurin was consistent across all FLT3 subtypes. The rate of severe adverse events was similar in the two groups. CONCLUSIONS: The addition of the multitargeted kinase inhibitor midostaurin to standard chemotherapy significantly prolonged overall and event-free survival among patients with AML and a FLT3 mutation. (Funded by the National Cancer Institute and Novartis; ClinicalTrials.gov number, NCT00651261 .).