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Background: Various glomerular pathologies have been reported in patients who have undergone haematopoietic stem cell transplantation (HSCT), but the data on clinico-pathological correlations and clinical outcome remain limited. Methods: We analysed the clinical and histopathological data of patients who had biopsy-proven de novo glomerular diseases after HSCT since 1999. Results: A total of 2204 patients underwent HSCT during the period 1999-2021, and 31 patients (1.4%) developed de novo glomerular diseases after a mean duration of 2.8 ± 2.7 years after HSCT. Fifteen of these patients (48.4%) had graft-versus-host-disease prior to or concomitant with renal abnormalities. Proteinuria and eGFR at the time of kidney biopsy were 4.1 ± 5.3 g/day and 50.8 ± 25.4 mL/min/1.73 m2, respectively. Kidney histopathologic diagnoses included thrombotic microangiopathy (TMA) (38.7%), membranous nephropathy (MN) (25.8%), mesangial proliferative glomerulonephritis (12.9%), minimal change disease (9.7%), focal segmental glomerulosclerosis (9.7%) and membranoproliferative glomerulonephritis (3.2%). Immunosuppressive treatment was given to patients who presented with nephrotic-range proteinuria and/or acute kidney injury, while renin-angiotensin-aldosterone blockade was given to all patients with proteinuria ≥1 g/day, with complete and partial response rates of 54.8% and 19.4%, respectively. One patient with TMA progressed to end-stage kidney disease after 24 weeks, and two patients, one with TMA and one with MN, (6.4%) progressed to chronic kidney disease (CKD) Stage ≥3. Kidney and patient survival rates were 96.6% and 83.5%, respectively, at 5 years. Conclusion: De novo glomerular diseases with diverse histopathologic manifestations affect 1.4% of patients after HSCT, and approximately 10% develop progressive CKD.
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Emerging dye pollution from textile industrial effluents is becoming more challenging for researchers worldwide. The contamination of water by dye effluents affects the living organisms in an ecosystem. Methylene blue (MB) and malachite green (MG) are soluble dyes with a high colour intensity even at low concentration and are hazardous to living organisms. The adsorption method is used in most wastewater plants for the removal of organic pollutants as it is cost-effective, has a high adsorption capacity, and good mechanical stabilities. In this study, a composite adsorbent was prepared by impregnating iron modified silica (FMS) onto polyurethane (PU) foam to produce an iron modified silica/polyurethane (FMS/PU) composite. The composite adsorbent was utilised in batch adsorption of the cationic dyes MB and MG. The effect of adsorption parameters such as the adsorbent load, pH, initial dye concentration, and contact time were discussed. Adsorption kinetics and isotherm were implemented to understand the adsorption mechanism for both dyes. It was found that the adsorption of MB and MG followed the pseudo-second order model. The Langmuir model showed a better fit than the Freundlich model for the adsorption of MB and MG, indicating that the adsorption occurred via the monolayer adsorption system. The maximum adsorption capacity of the FMS/PU obtained for MB was 31.7 mg/g, while for MG, it was 34.3 mg/g. The thermodynamic study revealed that the adsorption of MB and MG were exothermic and spontaneous at room temperature. In addition, the regeneration of FMS/PU was conducted to investigate the composite efficiency in adsorbing dyes for several cycles. The results showed that the FMS/PU composite could be regenerated up to four times when the regeneration efficiency dropped drastically to less than 20.0%. The impregnation of FMS onto PU foam also minimised the adsorbent loss into the environment.
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OBJECTIVES: Bendamustine is a standard treatment for low-grade B-cell lymphomas, and considered safe in clinical trials. Its safety in routine practice might be different. METHODS: We retrospectively analyzed the infection complications in an unselected cohort of patients treated with bendamustine over a nine-year period. Patients were regularly monitored for blood counts and cytomegalovirus (CMV) reactivation by antigen assay and polymerase chain reaction. They received granulocyte colony stimulating factor for neutropenia, and routine anti-pneumocystis and optional anti-fungal prophylaxis. RESULTS: There were 179 men and 127 women at a median age of 61.5 (20-90) years, 52% receiving bendamustine for relapsed/refractory disease. Malignancies included low-grade B-cell lymphomas (54%), myeloma (10%), T-cell lymphomas (11%), Hodgkin lymphoma (2%) and other lymphoid neoplasms (23%). Most patients had good performance status (Eastern Cooperative Oncology Group score: 0-1, 72%). CMV reactivation occurred in 58 patients (19%) at a median age of 68 (39-85) years. Univariate analysis showed CMV reactivation to be significantly associated with elevated lactate dehydrogenase (P = 0.045), decreased albumin (P = 0.003) and older age (reactivation versus no reactivation: 66.3 ± 11.4 versus 59.4 ± 14.5 years, P = 0.0016). Age remained the only significant risk on multivariate analysis. CMV reactivation resulted in retinitis (N = 4), ependymitis/ventriculitis (N = 1) and duodenitis/colitis (N = 1). Invasive fungal disease occurred in five patients (candidemia, N = 2; aspergillosis N = 1; cryptococcemia, N = 1; scedosporiosis, N-1). Nineteen patients had culture positive septicaemia. CONCLUSION: Our observations showed that even with a vigorous anti-infective strategy, bendamustine treatment was still associated with significant risks of bacterial and opportunistic viral and fungal infections.
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Infecciones Bacterianas , Infecciones por Citomegalovirus , Neoplasias Hematológicas , Linfoma de Células B , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/complicaciones , Clorhidrato de Bendamustina/efectos adversos , Infecciones por Citomegalovirus/etiología , Femenino , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The thrombopoietin mimetic eltrombopag (EPAG) is efficacious in clinical trials of newly diagnosed moderate (M), severe (S) and very severe (vS) aplastic anaemia (AA). Its use in routine practice and resource-constrained settings is not well described. Twenty-five men and 38 women at a median age of 54 (18-86) years with newly diagnosed AA treated consecutively in a 7-year period with EPAG (N = 6), EPAG/cyclosporine (CsA) (N = 33) and EPAG/CsA/anti-thymocyte globulin (ATG) (N = 24) were analyzed. Because EPAG was not reimbursed, peak doses ranged from 25 to 200 mg/day depending on affordability. EPAG/CsA-treated patients were older (median age: 61 years) with less severe AA (MAA, N = 15; SAA, N = 14; vSAA, N = 4), whereas EPAG/CsA/ATG-treated patients were younger (median age: 44 years) with more severe AA (MAA, N = 2; SAA, N = 12, vSAA, N = 10). The overall/trilineage response rates were 83%/50% for EPAG-treated patients; 79%/42% for EPAG/CsA-treated patients and 75%/63% for EPAG/CsA/ATG-treated patients. Adverse events included grade 1 liver derangement (N = 7) and grade 1 dyspepsia (N = 3). The 5-year overall survivals/failure-free survivals were 62%/80% for the entire cohort; 55%/75% for EPAG/CsA-treated patients and 82%/78% for EPAG/CsA/ATG-treated patients. EPAG showed robust efficacy in AA in routine practice. However, EPAG dosage and combinations remain to be optimized for AA of different severities.
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Anemia Aplásica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia Aplásica/inducido químicamente , Anemia Aplásica/tratamiento farmacológico , Suero Antilinfocítico/uso terapéutico , Benzoatos/efectos adversos , Ciclosporina/uso terapéutico , Femenino , Humanos , Hidrazinas/efectos adversos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Pirazoles , Resultado del Tratamiento , Adulto JovenRESUMEN
Immunoglobulin G4-related disease (IgG4-RD) has rarely been associated with lymphoid neoplasms, the spectrum of which remains unclear. B-cell lymphoid neoplasms (LN) associated with IgG4-RD diagnosed in a 4-year period were analysed. There were five men and three women at a median age of 76.5 (52-90) years; three with synchronous IgG4-RD and LN; three with IgG4-RD preceding LN by 2, 3, and 22 years; and two with LN preceding IgG4-RD by 2.5 and 7 years. All patients presented with disseminated lymphadenopathy. Monoclonal gammopathy of undetermined significance (MGUS)/smouldering multiple myeloma (SMM) was found in three patients, all with an IgGκ paraprotein. Levels of IgGκ and IgG4 correlated. Diffuse large B-cell lymphoma (DLBCL) was found in three patients, with one case showing co-existing lymphoma and IgG4-RD in the same lymph node biopsy. The remaining two cases were marginal zone lymphoma (MZL) developing in a lacrimal gland previously involved by IgG4-RD; and nodular lymphocyte predominant Hodgkin lymphoma (NLP-HL) diagnosed in a lymph node with concomitant IgG4-RD. Low-dose continuous prednisolone was given for MGUS/SMM, with both monoclonal IgGκ and IgG4 responding. Combination chemotherapy was given for DLBCL, with two patients achieving complete response and one patient dying from refractory lymphoma. The patient with MZL refused treatment, whereas the case of NLP-HL responded completely to chemotherapy. Our findings together with previous observations suggest that IgG4-RD has an increased risk of B-cell neoplasms. Patients with IgG4-RD presenting with lymphadenopathy require vigorous investigations to exclude lymphoid neoplasms.
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Enfermedad de Hodgkin/complicaciones , Enfermedad Relacionada con Inmunoglobulina G4/complicaciones , Linfadenopatía/complicaciones , Linfoma de Células B de la Zona Marginal/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Anciano , Anciano de 80 o más Años , Manejo de la Enfermedad , Femenino , Enfermedad de Hodgkin/terapia , Humanos , Inmunoglobulina G , Enfermedad Relacionada con Inmunoglobulina G4/terapia , Linfadenopatía/terapia , Linfoma de Células B de la Zona Marginal/terapia , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/terapiaRESUMEN
Graft-versus-host disease (GVHD) is an important complication after allogeneic haematopoietic stem cell transplantation (HSCT). Corticosteroids are the standard first-line treatment. Steroid-resistant/-dependent (SR/D) acute and chronic GVHD (aGVHD, cGVHD) lead to significant morbidity/mortality. The JAK2 inhibitor ruxolitinib has recently been shown in clinical trials to be effective in SR/D aGVHD and cGVHD. We retrospectively analysed the efficacy and safety of ruxolitinib in a cohort of SR/D aGVHD and cGVHD patients treated in a non-trial setting. In the aGVHD cohort, there were 14 men and 12 women, median age at 38 (19-63) years. At day 28 post-ruxolitinib, the overall response rate (ORR) was 86% (complete response, CR, 36%; partial response, PR, 50%). Continued ruxolitinib beyond day 28 resulted in a final CR of 68%. However, 3/15 (20%) of CR patients developed cGVHD. In the cGVHD cohort, there were 16 men and 15 women, median age at 33 (21-64) years. The ORR, CR and PR rates changed with continued ruxolitinib treatment, being 86%, 17% and 69% at 1 month; 79%, 38% and 41% at 3 months; and 83%, 52% and 31% at 6 months. Five patients had overlap GVHD, four of whom achieved CR. Multivariate analysis showed that superior overall survival and failure-free survival were associated with CR at day 28 for aGVHD, and CR at 1 year for cGVHD. Ruxolitinib treatment was efficacious for SR/D aGVHD and cGVHD, and continued treatment for at least 6 months was needed to maximize benefit.
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Enfermedad Injerto contra Huésped/tratamiento farmacológico , Nitrilos/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Enfermedad Aguda , Adulto , Enfermedad Crónica , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Humanos , Janus Quinasa 2/antagonistas & inhibidores , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Esteroides/uso terapéutico , Análisis de Supervivencia , Adulto JovenRESUMEN
The method of pre-irradiation grafting was used with the aid of electron beam (EB) accelerator to accomplish the grafting of polyamide 6 fibers (PA6) with glycidyl methacrylate (GMA). The extent to which GMA was grafted on PA6 was found to be markedly influenced by the absorbed dose of radiation and the reaction time of grafting. Trimethylamine (TMA) was afterwards employed for the functionalization of GMA-grafted fibers (PA6-g-GMA). A range of analyses (e.g., FTIR, FESEM, XRD, BET, and pHpzc) were carried out to determine the physiochemical and morphological properties of the fibrous adsorbent. p-Nitrophenol (PNP) adsorption from aqueous solution was conducted with the resulting TMA-(PA6-g-GMA) adsorbent. The adsorption behaviour of PNP on the fibrous adsorbent was clarified by investigating the adsorption kinetics and isotherm. According to the results, the adsorption of PNP on TMA-(PA6-g-GMA) reflected the pseudo-second order model. Meanwhile, the isotherm analysis revealed that the best description of the equilibrium data was provided by Redlich-Peterson model, followed closely by Langmuir isotherm model. The achieved adsorption capacity was highest at 176.036 mg/g. Moreover, the adsorption was indicated by the thermodynamic analysis to be spontaneous and exothermic. Regeneration and recycling of the adsorbent was possible for a minimum of five cycles with no reduction in adsorption capacity. It was concluded that the fibrous adsorbent could have applications for the removal of PNP at industrial pilot scale.
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The efficacy and safety of low-dose anti-PD1 antibodies in relapsed/refractory classical Hodgkin lymphoma (cHL) require confirmation. Pembrolizumab (100 mg every 3 weeks, Q3W) or nivolumab (40 mg Q2W) were administered to patients with relapsed/refractory cHL. In the pembrolizumab cohort (N = 11), who had failed a median of three (1-6) therapies (brentuximab vedotin [BV]: 91%; autologous hematopoietic stem cell transplantation [auto-HSCT]: 18%), the overall response rate (ORR) by positron emission tomography-computed tomography was 100% (metabolic complete response [mCR]: 73%; partial response [PR]: 27%). Median cumulative dose for achieving best response was 400 (300-800) mg. Median progression-free survival (PFS) was 35 months. Median overall survival (OS) was not reached. Adverse events (AEs) of grade 1-2 were observed in three patients. In the nivolumab cohort (N = 6), who had failed a median of three (2-6) therapies (BV: 50%; auto-HSCT: 17%; allogeneic HSCT: 34%), the ORR was 100% (mCR: 67%; PR: 17%; indeterminate response: 17%). Median cumulative dose for achieving best response was 160 (160-360) mg. Median PFS was 33 months. Median OS was not reached. AEs of grade 1-2 were observed in four patients, two of whom had pre-existing autoimmune conditions. Five patients with Epstein-Barr virus (EBV) positive Reed-Sternberg cells underwent monitoring of plasma EBV DNA, which became negative in four mCR patients but remained positive in one PR patient who died ultimately from refractory lymphoma. Low-dose pembrolizumab and nivolumab were highly efficacious and safe in relapsed/refractory cHL. These observations have significant financial implications in resource-constrained settings.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resistencia a Antineoplásicos , Femenino , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Nivolumab/administración & dosificación , Tomografía Computarizada por Tomografía de Emisión de Positrones , Retratamiento , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenAsunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Brentuximab Vedotina/administración & dosificación , Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4/metabolismo , Lenalidomida/administración & dosificación , Linfoma de Células T , Neoplasias Primarias Secundarias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Anciano , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Infecciones por Virus de Epstein-Barr/diagnóstico por imagen , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/etiología , Infecciones por Virus de Epstein-Barr/metabolismo , Etopósido/administración & dosificación , Humanos , Linfoma de Células T/diagnóstico por imagen , Linfoma de Células T/tratamiento farmacológico , Linfoma de Células T/metabolismo , Masculino , Neoplasias Primarias Secundarias/diagnóstico por imagen , Neoplasias Primarias Secundarias/tratamiento farmacológico , Neoplasias Primarias Secundarias/metabolismo , Neoplasias Primarias Secundarias/virología , Prednisolona/administración & dosificación , Vincristina/administración & dosificaciónRESUMEN
Clofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18- to 65-year-old AML patients refractory to first-line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high-dose cytarabine consolidation, with clofarabine (30 mg/m2 /d, Days 1-5), cytarabine (750 mg/m2 /d, Days 1-5), and mitoxantrone (12 mg/m2 /d, Days 3-5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT). The mutational profile of a 69-gene panel was evaluated. Twenty-six men and 26 women at a median age of 46 (22-65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematologic recovery, CRi: 21.2%). Twenty-two CR/CRi patients underwent allo-HSCT. The 2-year overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P = .005) and allo-HSCT (P = .005), and superior RFS and EFS were associated with allo-HSCT (P < .001). Remarkably, CR after CLAM and allo-HSCT resulted in 2-year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment-related mortality and the performance of allo-HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/tratamiento farmacológico , Adulto , Anciano , Neutropenia Febril Inducida por Quimioterapia/epidemiología , Clofarabina/administración & dosificación , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Mitoxantrona/administración & dosificación , Recurrencia Local de Neoplasia , Tasa de Supervivencia , Trombocitopenia/inducido químicamente , Trombocitopenia/epidemiología , Trasplante Homólogo , Adulto JovenRESUMEN
Iron and steel industries are among the contributors of CO2 emission in large volume into the atmosphere, causing detrimental effects to the environment and the ecosystem at large scale. These industries also generate solid wastes in the form of electric arc furnace (EAF) slag during operations which result in about 10-15% slag wastes per ton of steel produced. In this study, the EAF slags from an iron and steel-making factory in Klang, Malaysia was utilized for CO2 sequestration through direct aqueous mineral carbonation. According to the surface area analysis, the fresh EAF slag has a mesoporous structure, its elemental composition shows the presence of 20.91 wt.% of CaO that was used for the sequestration of CO2 through carbonation. The sequestration capacity was found to be 58.36 g CO2/kg of slag at ambient temperature in 3 h, with the liquid/solid (L/S) ratio of 5:1 and using <63µm particle size. Moreover, the shrinking core model (SCM) was used to analyze the solid-fluid reaction in a heterogeneous phase and the CO2 sequestration shows to be controlled by the product layer phase. The EAF slag is demonstrated to have the potential of CO2 sequestration at ambient temperature.
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Neoplasias Encefálicas/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Nivolumab/administración & dosificación , Anciano , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/metabolismo , Linfoma de Células B Grandes Difuso/patología , Imagen por Resonancia Magnética , MasculinoRESUMEN
BACKGROUND: Strategies using oral arsenic trioxide (As2 O3 ) are efficacious in relapsed acute promyelocytic leukemia (APL), but they have not been examined in newly diagnosed cases. METHODS: Sixty-two consecutive patients (24 men and 38 women) with a median age of 52 years (range, 22-85 years), 36% of whom had high-risk features, underwent induction with all-trans retinoic acid at 45 mg/m2 /d, oral As2 O3 at 10 mg/d, and ascorbic acid at 1 g/d (the all-trans retinoic acid-arsenic trioxide-ascorbic acid [AAA] regimen) for 6 weeks (with patients younger than 70 years additionally receiving daunorubicin at 50 mg/m2 /d × 3); they then underwent consolidation with 2 monthly cycles of daunorubicin (50 mg/m2 /d × 2) and cytarabine (100 mg/m2 /d × 5) and received AAA maintenance (2 weeks every 8 weeks) for 2 years. A contemporaneous cohort of 37 newly diagnosed patients (15 men and 22 women) with a median age of 51 years (range, 23-78 years), not consenting to oral As2 O3 induction but receiving similar induction, consolidation, and AAA maintenance, served as a comparator group; 46% of these patients had high-risk features. RESULTS: The oral As2 O3 induction cohort showed a complete remission (CR) rate of 100%. After a median of 37 months (range, 13-82 months), there were no relapses, so conventional risks (age, leukocyte and platelet counts, and Fms-like tyrosine kinase 3 [FLT3] mutations) were not relevant. The leukemia-free survival (LFS) and overall survival (OS) rates were 100% at 3 years and 94.1% at 5 years. The non-As2 O3 induction cohort showed a CR rate of 100%. After a median of 52 months (range, 14-77 months), there were 3 relapses (8%). Comparable patients in the oral As2 O3 induction and non-As2 O3 induction cohorts showed similar OS, but LFS was significantly superior in the oral As2 O3 induction cohort. CONCLUSIONS: The incorporation of oral As2 O3 into induction for newly diagnosed APL was safe and decreased relapses.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Promielocítica Aguda/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trióxido de Arsénico/administración & dosificación , Femenino , Humanos , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Tretinoina/administración & dosificación , Adulto JovenRESUMEN
BACKGROUND: For patients who have acute promyelocytic leukemia (APL) in second complete remission (CR2), optimal postremission strategies remain undefined. METHODS: The role of an oral arsenic trioxide (As2 O3 )-based regimen in the management of patients who had APL in CR2 was examined. RESULTS: Seventy-three patients with APL in first relapse (R1) were studied. Oral As2 O3 -based reinduction resulted uniformly in CR2, irrespective of previous As2 O3 exposure. All patients received oral As2 O3 -based maintenance in CR2. At a median follow-up of 94 months (range, 9-205 months), 43 patients (58.9%) were still in CR2, and 49 (67.1%) had finished the planned 2-year CR2 maintenance with all-trans retinoic acid, oral As2 O3 , and ascorbic acid. Reinduction and maintenance treatments were well tolerated. Grade 1 and 2 headache occurred in 20 patients (27.4%). Hepatotoxicity, all in the form of transaminitis, occurred in 35 patients (47.9%; grade 1 and 2, n = 26; grade 3 and 4, n = 9). Three patients had self-limiting QTc prolongation. The 10-year leukemia-free survival rate was 56.8%. Thirty patients developed R2. Oral As2 O3 -based reinduction led to CR3 in 27 patients (90%). Post-CR3 strategies included autologous hematopoietic stem cell transplantation and oral As2 O3 maintenance. At a post-CR3 follow-up of 30 months (range, 3-166 months), 11 patients were still in CR3. The 5-year and 10-year overall survival rates in the R1 cohort were 79.5% and 67.3%, respectively. Prior receipt of oral As2 O3 maintenance in CR1 was the only risk factor for inferior leukemia-free survival. Central nervous system involvement occurred in 15 patients, including 5 who remained alive. Relapse during oral As2 O3 therapy was the only significant risk factor for central nervous system involvement. CONCLUSIONS: For patients with relapsed APL, As2 O3 remained effective despite repeated As2 O3 exposures. Oral As2 O3 maintenance was an effective postremission strategy for CR2. Cancer 2018;124:2316-26. © 2018 American Cancer Society.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Trióxido de Arsénico/administración & dosificación , Leucemia Promielocítica Aguda/terapia , Recurrencia Local de Neoplasia/terapia , Inducción de Remisión/métodos , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trióxido de Arsénico/efectos adversos , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Femenino , Cefalea/inducido químicamente , Cefalea/diagnóstico , Cefalea/epidemiología , Trasplante de Células Madre Hematopoyéticas , Hong Kong/epidemiología , Humanos , Leucemia Promielocítica Aguda/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Factores de Tiempo , Trasplante Autólogo , Tretinoina/administración & dosificación , Tretinoina/efectos adversos , Adulto JovenRESUMEN
OBJECTIVE: The thrombopoietin mimetic eltrombopag has been used in clinical trials for the frontline and salvage treatment of aplastic anaemia (AA). Eltrombopag was investigated in AA patients on a non-trial all-comer basis. METHODS: Consecutive newly diagnosed and relapsed/refractory AA patients were treated with eltrombopag. RESULTS: In a 4.5-year period, 20 consecutive AA patients (newly diagnosed, N = 10; relapsed/refractory, N = 10) at a median age of 47 (22-84) years were treated with eltrombopag. For newly diagnosed patients, the frontline use of eltrombopag (concomitant medications: anti-thymocyte globulin, ATG, and ciclosporin, N = 4; ciclosporin, N = 5; nil, N = 1) at a median maximum dose of 150 (50-300)â mg/day led to an overall response rate (ORR) of 90% (trilineage: 60%; neutrophil: 20%; platelet: 10%). After a median follow-up of 47 (14-179) weeks, responses were maintained in all cases. In relapsed/refractory patients, eltrombopag at a median maximum dose of 150 (50-300)â mg/day led to an ORR of 50% (trilineage: 40%; neutrophil: 10%), with responses maintained after a median follow-up of 115 (53-253) weeks. Adverse effects included reversible skin pigmentation (observed in all patients taking eltrombopag at ≥150â mg/day), dyspepsia, and liver function derangement. CONCLUSION: In a routine haematological practice, the use of eltrombopag in AA patients was feasible, safe, and associated with very favourable responses.
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Anemia Aplásica/tratamiento farmacológico , Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Pirazoles/uso terapéutico , Adulto , Anemia Aplásica/diagnóstico , Benzoatos/administración & dosificación , Benzoatos/efectos adversos , Biomarcadores , Terapia Combinada , Manejo de la Enfermedad , Resistencia a Medicamentos , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Hidrazinas/administración & dosificación , Hidrazinas/efectos adversos , Masculino , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Recurrencia , Trombopoyetina/administración & dosificación , Trombopoyetina/efectos adversos , Trombopoyetina/uso terapéutico , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Terapia Molecular Dirigida , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Anciano de 80 o más Años , Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Asparaginasa/administración & dosificación , Evaluación de Medicamentos , Resistencia a Antineoplásicos , Resultado Fatal , Femenino , Humanos , Linfoma Extranodal de Células NK-T/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Nivolumab , Receptor de Muerte Celular Programada 1/inmunología , Recurrencia , Terapia RecuperativaRESUMEN
Sensitization to inhaled allergens is dependent on activation of conventional dendritic cells (cDCs) and on the adaptor molecule, MyD88. However, many cell types in the lung express Myd88, and it is unclear how signaling in these different cell types reprograms cDCs and leads to allergic inflammation of the airway. By combining ATAC-seq with RNA profiling, we found that MyD88 signaling in cDCs maintained open chromatin at select loci even at steady state, allowing genes to be rapidly induced during allergic sensitization. A distinct set of genes related to metabolism was indirectly controlled in cDCs through MyD88 signaling in airway epithelial cells (ECs). In mouse models of asthma, Myd88 expression in ECs was critical for eosinophilic inflammation, whereas Myd88 expression in cDCs was required for Th17 cell differentiation and consequent airway neutrophilia. Thus, both cell-intrinsic and cell-extrinsic MyD88 signaling controls gene expression in cDCs and orchestrates immune responses to inhaled allergens.
Asunto(s)
Asma/inmunología , Células Dendríticas/inmunología , Eosinófilos/inmunología , Hipersensibilidad/inmunología , Factor 88 de Diferenciación Mieloide/metabolismo , Mucosa Respiratoria/fisiología , Células Th17/inmunología , Administración por Inhalación , Alérgenos/inmunología , Animales , Comunicación Celular , Diferenciación Celular , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Humanos , Inmunización , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 88 de Diferenciación Mieloide/genética , Transducción de SeñalAsunto(s)
Anticuerpos Biespecíficos/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Diagnóstico Diferencial , Tricosporonosis/diagnóstico , Infección por el Virus de la Varicela-Zóster/diagnóstico , Adulto , Anticuerpos Biespecíficos/uso terapéutico , Antifúngicos/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antivirales/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/complicaciones , Femenino , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Recurrencia , Terapia Recuperativa , Tricosporonosis/tratamiento farmacológico , Tricosporonosis/etiologíaRESUMEN
OBJECTIVE: To define the positron emission tomography/computed tomography (PET/CT) features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), a rare malignancy in European and North American populations and the most common form of primary intestinal T-cell lymphoma in Asian populations. METHODS: 18F-fluorodeoxyglucose (FDG) PET/CT findings of a cohort of MEITL patients were retrospectively analyzed. RESULTS: Eight men and four women with MEITL investigated by PET/CT at diagnosis and relapse were retrospectively analyzed. On presentation, the primary involved sites were the small bowel (N = 8), large bowel (N = 2), stomach (N = 1) and small and large bowels (N = 1). The uninvolved small bowel did not show increased FDG-avidity to suggest enteropathy. On presentation, lymph nodes and other organs were involved in seven cases (58%). The primary lesions were hypermetabolic except in one case, where the colonic lesion was eumetabolic. At relapse, the stomach and large bowel might be involved even if the primary tumours arose from the small bowel, and multiple extra-intestinal metastases occurred. Interestingly, thoracic structures and the brain were frequently involved (50% and 25% respectively). CONCLUSION: These findings showed that in contrast to classical enteropathy-associated T-cell lymphoma, where the small bowel is the exclusive primary site (owing to its origin from coeliac disease) and distant metastases even during relapse are exceptional, MEITL might on presentation and during relapse involve any part of the gut, and metastasize to multiple extra-intestinal sites.