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1.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32883808

RESUMO

BACKGROUND: Children with isolated neutropenia (absolute neutrophil count [ANC] <1500/µL) are frequently referred to pediatric hematology and oncology clinics for further diagnostic evaluation. Scant literature exists on interventions and outcomes for isolated neutropenia. We hypothesized that children will have resolution of their neutropenia without the need for intervention(s) by a pediatric hematologist and oncologist. METHODS: We performed a 5.5-year institutional review board-approved retrospective chart review of children referred to our pediatric hematology and oncology clinics for isolated neutropenia. Neutropenia was categorized as mild (ANC of 1001-1500/µL), moderate (ANC of 500-1000 µL), severe (ANC of 201-500/µL), or very severe (ANC of ≤200/µL). RESULTS: Among 155 children referred with isolated neutropenia, 45 (29%) had mild neutropenia, 65 (42%) had moderate neutropenia, 30 (19%) had severe neutropenia, and 15 (10%) had very severe neutropenia. Only 29 (19%) children changed to an ANC category lower than their initial referral category. At a median follow-up of 12 months, 101 children had resolution of neutropenia, 40 children had mild neutropenia, 10 children had moderate neutropenia, 3 children had severe neutropenia, and 1 patient had very severe neutropenia. A specific diagnosis was not identified in most (54%) children. The most common etiologies were viral suppression (16%), autoimmune neutropenia (14%), and drug-induced neutropenia (8%). Black children had a 3.5 higher odds of having persistent mild neutropenia. Six (4%) children received granulocyte colony-stimulating factor therapy. CONCLUSIONS: Most children referred for isolated neutropenia do not progress in severity and do not require subspecialty interventions or hospitalizations.


Assuntos
Neutropenia/epidemiologia , Encaminhamento e Consulta/estatística & dados numéricos , Adolescente , Afro-Americanos/estatística & dados numéricos , Anticorpos Antinucleares/análise , Americanos Asiáticos/estatística & dados numéricos , Doenças Autoimunes/complicações , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Criança , Pré-Escolar , Progressão da Doença , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Hematologia , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Oncologia , Neutropenia/diagnóstico , Neutropenia/tratamento farmacológico , Neutropenia/etiologia , Remissão Espontânea , Estudos Retrospectivos , Viroses/complicações
2.
Nat Commun ; 11(1): 4387, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873795

RESUMO

The role of neutrophils in solid tumor metastasis remains largely controversial. In preclinical models of solid tumors, both pro-metastatic and anti-metastatic effects of neutrophils have been reported. In this study, using mouse models of breast cancer, we demonstrate that the metastasis-modulating effects of neutrophils are dictated by the status of host natural killer (NK) cells. In NK cell-deficient mice, granulocyte colony-stimulating factor-expanded neutrophils show an inhibitory effect on the metastatic colonization of breast tumor cells in the lung. In contrast, in NK cell-competent mice, neutrophils facilitate metastatic colonization in the same tumor models. In an ex vivo neutrophil-NK cell-tumor cell tri-cell co-culture system, neutrophils are shown to potentially suppress the tumoricidal activity of NK cells, while neutrophils themselves are tumoricidal. Intriguingly, these two modulatory effects by neutrophils are both mediated by reactive oxygen species. Collectively, the absence or presence of NK cells, governs the net tumor-modulatory effects of neutrophils.


Assuntos
Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Neoplasias Mamárias Animais/imunologia , Neutropenia/prevenção & controle , Neutrófilos/imunologia , Animais , Linhagem Celular Tumoral/transplante , Técnicas de Cocultura , Modelos Animais de Doenças , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Injeções Intravenosas , Pulmão/citologia , Pulmão/imunologia , Pulmão/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/secundário , Glândulas Mamárias Animais/citologia , Glândulas Mamárias Animais/imunologia , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Animais/sangue , Neoplasias Mamárias Animais/complicações , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Endogâmicos NOD , Neutropenia/sangue , Neutropenia/etiologia , Neutropenia/imunologia , Neutrófilos/efeitos dos fármacos , Cultura Primária de Células
3.
Lancet Haematol ; 7(9): e649-e659, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32758434

RESUMO

BACKGROUND: Avadomide (CC-122) is a novel oral cereblon-modulating agent with promising activity in non-Hodgkin lymphoma. We aimed to examine the safety and preliminary activity of avadomide plus obinutuzumab in patients with relapsed or refractory non-Hodgkin lymphoma. METHODS: CC-122-NHL-001 was a phase 1b dose escalation and expansion study at eight sites in France, Italy, and the Netherlands. Eligible patients (aged ≥18 years) had histologically confirmed CD20-positive relapsed or refractory non-Hodgkin lymphoma, had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had received previous treatment. In the dose expansion phase, only patients with previously treated relapsed or refractory follicular lymphoma (grade 1, 2, or 3a) were included. Avadomide was administered in escalating doses and two formulations: active pharmaceutical ingredient in capsule in 1·0 mg, 2·0 mg, 3·0 mg, and 4·0 mg doses and as formulated capsules in 3·0 mg and 4·0 mg doses orally once daily on days 1-5 followed by 2 days off (5-7-day schedule) every week of each 28-day cycle. Obinutuzumab 1000 mg was administered intravenously on days 2, 8, and 15 of cycle 1 and day 1 of cycles 2-8. Primary objectives were to determine the safety and tolerability, the non-tolerated dose, maximum tolerated dose, and recommended phase 2 dose (RP2D). All patients who received treatment were included in the safety analyses. Efficacy-evaluable patients completed at least one cycle of treatment and had baseline and at least one post-baseline assessment. The study is registered with ClinicalTrials.gov, NCT02417285 and EudraCT 2014-003333-26, and is ongoing. FINDINGS: Between June 24, 2015, and Dec 5, 2018, 73 patients were enrolled and treated; 19 had diffuse large B-cell lymphoma, 53 follicular lymphoma, and one marginal zone lymphoma. Median follow-up was 253 days (IQR 127-448). The median number of previous anticancer regimens was three (IQR 2-4). The maximum tolerated dose and non-tolerated dose were not reached in the dose escalation phase. On the basis of safety and pharmacokinetic-pharmacodynamic data, the avadomide RP2D was established as 3·0 mg as formulated capsules on a 5-7-day schedule in combination with 1000 mg of obinutuzumab. Patients enrolled in the expansion cohort received the established RP2D of avadomide. Across all doses, three patients had dose-limiting toxicities; one patient treated at the RP2D had dose-limiting toxicity (grade 3 sepsis). The most common adverse events of grade 3 and above were neutropenia (41 [56%] of 73) and thrombocytopenia (17 [23%] of 73). 34 (47%) patients had serious adverse events, which were considered to be avadomide-related in 23 (32%) of 73 patients and obinutuzumab-related in 20 (27%) of 73 patients. Two treatment-related deaths occurred, one owing to tumour flare and one from acute myeloid leukaemia after study discontinuation. INTERPRETATION: Avadomide plus obinutuzumab has a manageable toxicity, being a tolerable treatment option for most patients. Although the prespecified threshold for activity was not met in the trial, we believe that the preliminary antitumour activity of cereblon modulators plus next-generation anti-CD20 antibodies in heavily pretreated relapsed or refractory non-Hodgkin lymphoma warrants further investigation as a chemotherapy-free option in this setting. FUNDING: Celgene Corporation.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Piperidonas/uso terapêutico , Quinazolinonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Meia-Vida , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Neutropenia/patologia , Piperidonas/efeitos adversos , Piperidonas/farmacocinética , Quinazolinonas/efeitos adversos , Quinazolinonas/farmacocinética , Recidiva , Índice de Gravidade de Doença , Trombocitopenia/etiologia , Trombocitopenia/patologia , Resultado do Tratamento
4.
Rev Chilena Infectol ; 37(1): 77-81, 2020 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-32730404

RESUMO

The episodes of febrile neutropenia are severe cases that require an exhaustive etiological study and a quick start of antimicrobial agents. Within the possible microorganisms, fungal origins are also found, and depending on its tissue invasion, they can reach a high mortality rate. A case of a pediatric patient who suffered from acute myeloid leukemia is reported, and after his induction chemotherapy, the patient showed an episode of febrile neutropenia, which matches a rhinosinusal infection caused by Exserohilum rostratum, a filamentous fungi that is uncommonly associated with pathological cases. An antifungal therapy and an early surgical treatment were started, which lead to a positive response, without complications to the patient. After the monitoring and receiving secondary prophylaxis during the episodes of neutropenia, the patient hasn't presented new injuries nor rhinosinusal damage.


Assuntos
Antifúngicos , Ascomicetos , Leucemia Mieloide Aguda , Micoses , Sinusite , Antifúngicos/uso terapêutico , Ascomicetos/isolamento & purificação , Criança , Humanos , Leucemia Mieloide Aguda/complicações , Micoses/complicações , Micoses/tratamento farmacológico , Neutropenia/etiologia , Sinusite/complicações , Sinusite/tratamento farmacológico , Sinusite/microbiologia , Resultado do Tratamento
7.
Cochrane Database Syst Rev ; 5: CD013238, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32395825

RESUMO

BACKGROUND: Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of glioblastomas, however clinical improvements are difficult to obtain for many reasons. The current standard of care involves maximal safe surgical resection followed by chemoradiation and then adjuvant chemotherapy European Organisation for Research and Treatment of Cancer and the NCIC Clinical Trials Group (EORTC-NCIC) protocol with a median survival of 14.6 months. Successive phase III international randomised controlled studies have failed to significantly demonstrate survival advantage with newer drugs. Epidermal growth factor receptor (EGFR) is observed to be aberrant in 30% to 60% of glioblastomas. The receptor aberrancy is driven by abnormal gene amplification, receptor mutation, or both, in particular the extracellular vIII domain. EGFR abnormalities are common in solid tumours, and the advent of anti-EGFR therapies in non-small cell lung cancer and colorectal adenocarcinomas have greatly improved clinical outcomes. Anti-EGFR therapies have been investigated amongst glioblastomas, however questions remain about its ongoing role in glioblastoma management. This review aimed to report on the available evidence to date and perform a systematic analysis on the risks and benefits of use of anti-EGFR therapies in glioblastomas. OBJECTIVES: To evaluate the efficacy and harms of anti-EGFR therapies for glioblastoma in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, EBM Reviews databases, with supplementary handsearches to identify all available and relevant studies to 20 April 2020. SELECTION CRITERIA: All randomised controlled trials (RCTs) using anti-EGFR therapies in adults with glioblastoma were eligible for inclusion. Anti-EGFR therapies included tyrosine kinase inhibitors, monoclonal antibodies, or vaccines. The comparison included investigational product added to standard of care versus standard of care or placebo, or investigational product against standard of care or placebo. DATA COLLECTION AND ANALYSIS: The authorship team screened the search results and recorded the extracted data for analysis. We used standard Cochrane methodology to performed quantitative meta-analysis if two or more studies had appropriate and available data. Otherwise, we conducted a qualitative and descriptive analysis. We used the GRADE system to rate the certainty of the evidence. The analysis was performed along the two clinical settings: first-line (after surgery) and recurrent disease (after failure of first line treatment). Where information was available, we documented overall survival, progression-free survival, adverse events, and quality of life data from eligible studies. MAIN RESULTS: The combined searches initially identified 912 records (after removal of duplicates), and further screening resulted in 19 records for full consideration. We identified nine eligible studies for inclusion in the review. There were three first-line studies and six recurrent studies. Five studies used tyrosine kinase inhibitors (TKIs); two studies used monoclonal antibodies; and two studies used targeted vaccines. More recent studies presented greater detail in the conduct of their studies and thus had a lower risk of bias. We observed no evidence benefit in overall survival with the use of anti-EGFR therapy in the first-line or recurrent setting (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76 to 1.04; 3 RCTs, 1000 participants, moderate-certainty evidence; and HR 0.79, 95% CI 0.51 to 1.21, 4 RCTs, 489 participants, low-certainty evidence, respectively). All the interventions were generally well tolerated with low-certainty evidence for lymphopenia (odds ratio (OR) 0.97, 95% CI 0.19 to 4.81; 4 RCTs, 1146 participants), neutropenia (OR 1.29, 95% CI 0.82 to 2.03; 4 RCTs, 1146 participants), and thrombocytopenia (OR 3.69, 95% CI 0.51 to 26.51; 4 RCTs, 1146 participants). A notable toxicity relates to ABT-414, where significant ocular issues were detected. The addition of anti-EGFR therapy showed no evidence of an increase in progression-free survival (PFS) in the first-line setting (HR 0.94, 95% CI 0.81 to 1.10; 2 RCTs, 894 participants, low-certainty evidence). In the recurrent setting, there was an increase in PFS with the use of anti-EGFR therapy (HR 0.75, 95% CI 0.58 to 0.96, 3 RCTs, 275 participants, low-certainty evidence). The available quality of life assessment data showed that anti-EGFR therapies were neither detrimental or beneficial when compared to standard care (not estimable). AUTHORS' CONCLUSIONS: In summary, there is no evidence of a demonstrable overall survival benefit with the addition of anti-EGFR therapy in first-line and recurrent glioblastomas. Newer drugs that are specially designed for glioblastoma targets may raise the possibility of success in this population, but data are lacking at present. Future studies should be more selective in pursuing people displaying specific EGFR targets.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/mortalidade , Vacinas Anticâncer/uso terapêutico , Progressão da Doença , Glioblastoma/mortalidade , Humanos , Linfopenia/etiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/etiologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombocitopenia/etiologia
8.
Pediatr Blood Cancer ; 67(6): e28140, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32275120

RESUMO

BACKGROUND: Children with cancer experience a wide range of conditions that require urgent evaluation in the emergency department (ED), yet variation in admission rates is poorly documented. PROCEDURE: We performed a retrospective cohort study using the Pediatric Health Information System of ED encounters by children with cancer between July 2012 and June 2015. We compared demographics for admitted versus discharged using univariate statistics, and calculated admission rates by hospital, diagnosis, day of the week, and weekend versus weekday. We assessed the degree of interhospital admission rates using the index of dispersion (ID). RESULTS: Children with cancer had 60 054 ED encounters at 37 hospitals. Overall, 62.5% were admitted (range 43.2%-92.1%, ID 2.6) indicating overdispersed admission rates with high variability. Children with cancer that visited the ED for a primary diagnosis of fever experienced the largest amount of variability in admission with rates ranging from 10.4% to 74.1% (ID 8.1). Less variability existed among hospital admission rates for both neutropenia (range 60%-100%, ID 1.0) and febrile neutropenia (FN) (range 66.7%-100%, ID 0.83). Admission rates by day of the week did not demonstrate significant variability for any of the scenarios examined (overall P = 0.91). There were no differences by weekend versus weekday either (overall P = 0.52). CONCLUSION: The percentage of children with cancer admitted through the ED varies widely by institution and diagnosis. Standardization of best practices for children with cancer admitted through the ED should be an area of continued improvement.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Febre/diagnóstico , Sistemas de Informação em Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Neoplasias/complicações , Neutropenia/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Febre/etiologia , Febre/prevenção & controle , Seguimentos , Humanos , Lactente , Recém-Nascido , Classificação Internacional de Doenças , Masculino , Neutropenia/etiologia , Neutropenia/prevenção & controle , Prognóstico , Estudos Retrospectivos , Adulto Jovem
10.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32144121

RESUMO

A previously healthy 9-year-old immigrant girl from Mexico was evaluated in the emergency department (ED) with one week of fatigue, fevers, rhinorrhea, and cough. She initially presented to her primary pediatrician, where a complete blood count revealed neutropenia, prompting referral to the ED. In the ED, she was found to be influenza A-positive. Because of dehydration, she received intravenous fluids and was admitted to the pediatric hospital medicine service. After 2 days, influenza symptoms improved, and oral intake increased. However, she was noted to have decreased bilateral lower-extremity strength, absent Achilles reflexes, decreased lower-extremity sensation and proprioception, a positive result on the Romberg sign, and abnormal heel-to-shin testing results. These findings prompted an urgent neurology consultation. After extensive imaging, laboratory evaluation, and further consultations, a diagnosis was established.


Assuntos
Anemia/etiologia , Transtornos Neurológicos da Marcha/etiologia , Influenza Humana/complicações , Debilidade Muscular/etiologia , Neutropenia/etiologia , Deficiência de Vitamina B 12/diagnóstico , Antivirais/uso terapêutico , Criança , Diagnóstico Diferencial , Fadiga/etiologia , Feminino , Febre/etiologia , Transtornos Neurológicos da Marcha/diagnóstico , Humanos , Influenza Humana/tratamento farmacológico , Oseltamivir/uso terapêutico , Doenças da Medula Espinal/complicações , Doenças da Medula Espinal/diagnóstico , Deficiência de Vitamina B 12/complicações , Vômito/etiologia
11.
Mol Cells ; 43(2): 139-144, 2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32041395

RESUMO

Somatic RUNX1 mutations are found in approximately 10% of patients with de novo acute myeloid leukemia (AML), but are more common in secondary forms of myelodysplastic syndrome (MDS) or AML. Particularly, this applies to MDS/AML developing from certain types of leukemia-prone inherited bone marrow failure syndromes. How these RUNX1 mutations contribute to the pathobiology of secondary MDS/AML is still unknown. This mini-review focusses on the role of RUNX1 mutations as the most common secondary leukemogenic hit in MDS/AML evolving from severe congenital neutropenia (SCN).


Assuntos
Síndrome Congênita de Insuficiência da Medula Óssea/etiologia , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Leucemia Mieloide Aguda/complicações , Neutropenia/congênito , Síndrome Congênita de Insuficiência da Medula Óssea/patologia , Progressão da Doença , Humanos , Leucemia Mieloide Aguda/patologia , Mutação , Neutropenia/etiologia , Neutropenia/patologia
12.
Ann N Y Acad Sci ; 1466(1): 83-92, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32083314

RESUMO

Cyclic neutropenia (CyN) is a hematologic disorder in which peripheral blood absolute neutrophil counts (ANCs) show cycles of approximately 21-day intervals. The majority of CyN patients harbor ELANE mutations, but the mechanism of ANC cycling is unclear. We performed analysis of bone marrow (BM) subpopulations in CyN patients at the peak and the nadir of the ANC cycle and detected high proportions of BM hematopoietic stem cells (HSCs) and hematopoietic stem and progenitor cells (HSPCs) at the nadir of the ANC cycle, as compared with the peak. BM HSPCs produced fewer granulocyte colony-forming unit colonies at the ANC peak. To investigate the mechanism of cycling, we found that mRNA expression levels of ELANE and unfolded protein response (UPR)-related genes (ATF6, BiP (HSPA5), CHOP (DDIT3), and PERK (EIF2AK3)) were elevated, but antiapoptotic genes (Bcl-2 (BCL2) and bcl-xL (BCL2L1)) were reduced in CD34+ cells tested at the ANC nadir. Moreover, HSPCs revealed increased levels of reactive oxygen species and gH2AX at the ANC nadir. We suggest that in CyN patients, some HSPCs escape the UPR-induced endoplasmic reticulum (ER) stress and proliferate in response to granulocyte colony-stimulating factor (G-CSF) to a certain threshold at which UPR again affects the majority of HSPCs. There is a cyclic balance between ER stress-induced apoptosis of HSPCs and compensatory G-CSF-stimulated HSPC proliferation followed by granulocytic differentiation.


Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Elastase de Leucócito/genética , Neutropenia/etiologia , Resposta a Proteínas não Dobradas/fisiologia , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Medula Óssea/patologia , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estresse do Retículo Endoplasmático/genética , Seguimentos , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Hematopoese/efeitos dos fármacos , Hematopoese/genética , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/patologia , Células-Tronco Hematopoéticas/fisiologia , Humanos , Elastase de Leucócito/fisiologia , Mutação , Neutropenia/tratamento farmacológico , Neutropenia/metabolismo , Neutropenia/patologia , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Resposta a Proteínas não Dobradas/genética
13.
Medicine (Baltimore) ; 99(1): e18624, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895820

RESUMO

The purpose of this study was to evaluate neutropenia following intravenous immunoglobulin (IVIG) therapy in adults with immune thrombocytopenic purpura (ITP).Our analysis included 88 patients with ITP, who received IVIG from January 2006 to March 2016, at Pusan National University Hospital in Korea. Their white blood cell (WBC) count and absolute neutrophil count (ANC) before and after IVIG treatment were analyzed.Of 88 patients, 24 patients (27.3%) were male, and 64 patients (72.7%) were female. Neutropenia developed in 8 patients (18.7%) after IVIG treatment. In patients with a decrease in WBC count and ANC compared to baseline, median WBC count decreased from 6280/µL to 4530/µL after IVIG therapy, and median ANC decreased from 3840/µL to 2840/µL after IVIG therapy. The neutropenia induced by IVIG had resolved spontaneously after several days, and the mean recovery time was 8.72 days after the completion of the IVIG treatment. During the neutropenic episodes, only one patient developed neutropenic fever, which subsided soon without any treatment.The results of this study suggest that IVIG may cause neutropenia commonly in adults with ITP, and it seems to be transient and self-limited. This study is meaningful as the first report that not only pediatric ITP patients may develop neutropenia post IVIG administration, but also adult patients suffering ITP.


Assuntos
Imunoglobulinas Intravenosas/efeitos adversos , Neutropenia/etiologia , Púrpura Trombocitopênica Idiopática/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/imunologia , Estudos Retrospectivos , Adulto Jovem
14.
J Pediatr Hematol Oncol ; 42(2): 107-112, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31895216

RESUMO

Infections, drugs, malignancies, immunodeficiency, and autoimmunity may cause neutropenia. In primary autoimmune neutropenia, anti-neutrophil antibodies (ANeuA) bind to membrane antigens of neutrophils, which give rise to peripheral destruction of neutrophils. However, it is not always easy to detect these antibodies. This study aims to investigate the etiology of neutropenia, and at the same time to evaluate the immune mechanisms by ANeuA testing using granulocyte indirect immunofluorescence test. In our study, 310 neutropenic patients who were between 3 months and 18 years of age were evaluated. ANeuA screening tests were performed in 108 neutropenic patients (group 1), and these patients were divided into 2 subgroups as persistent neutropenia (group 1P, n=12) and recovered neutropenia (group 1R, n=96). Besides, a control group in the same age range was formed, consisting of 39 non-neutropenic children (group 2). ANeuA serum levels were also checked in these groups, and no statistically significant difference could be found between groups 1 and 2, or between groups 1P and 1R, regarding ANeuA levels. As a conclusion, our study was the first comprehensive research in Turkey investigating the large-scale etiology of neutropenia. Moreover, while ANeuA screening tests did not provide sufficient insight for immune neutropenia, we argue that it is not necessary for routine use and that further research in the etiology of neutropenia is required.


Assuntos
Autoanticorpos/imunologia , Autoimunidade/imunologia , Biomarcadores/análise , Granulócitos/imunologia , Neutropenia/classificação , Neutrófilos/imunologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neutropenia/diagnóstico , Neutropenia/etiologia , Prognóstico , Centros de Atenção Terciária
15.
Int J Radiat Oncol Biol Phys ; 106(2): 340-348, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655197

RESUMO

PURPOSE: Local persistence and relapse of disease in the gross tumor volume (GTV) account for the majority of treatment failures after standard chemoradiation therapy. The primary objective of this phase 1 trial was to define the maximum tolerated dose (MTD) of a hyperfractionated radiation therapy (HFRT) boost to the GTV with concurrent weekly paclitaxel and carboplatin after standard-dose chemoradiation therapy, using image guided intensity modulated radiation therapy techniques. METHODS AND MATERIALS: Eligible patients were given weekly doses of paclitaxel (45 mg/m2) and carboplatin (area under the curve 1.5) for 5 weeks with concurrent radiation therapy (50 Gy), immediately followed by an HFRT boost to the GTV with the same chemotherapy regimen. The boost doses were escalated in increments of 7.2 Gy delivered in 6 twice-daily fractions of 1.2 Gy using a modified Fibonacci design. Once the MTD was established, additional patients were treated at that dose to determine the safety. RESULTS: Thirty-one patients fulfilled the inclusion criteria. The incidence of dose-limiting toxicity was 0 of 3, 0 of 3, 0 of 3, 1 of 6 (grade 4 esophagitis), 0 of 3, and 2 of 3 (1 case each of grade 5 esophageal fistula and grade 3 pneumotitis) at 7.2, 14.4, 21.6, 28.8, 36, and 43.2 Gy, respectively, indicating an MTD of 36 Gy. Ten patients treated with this MTD showed no dose-limiting toxicities. The most common acute grade 3 or greater toxicities were esophagitis (26%) and neutropenia (19%). Late toxicity of grade 2 esophageal stricture occurred in 4 patients. The overall response rate was 84% (95% confidence interval, 42%-93%) in the entire cohort. The 1-year local control rate was 100% among those receiving a cumulative dose of the MTD or greater. CONCLUSIONS: The MTD of the HFRT boost after standard chemoradiation therapy in the setting of concurrent chemotherapy was 36 Gy, resulting in the cumulative tumor dose of 86 Gy in patients primarily with advanced intrathoracic/cervical esophageal squamous cell carcinomas and not adenocarcinomas of the gastroesophageal junction. A phase 2 study to further evaluate this regimen is underway.


Assuntos
Quimiorradioterapia/efeitos adversos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago/terapia , Dose Máxima Tolerável , Radioterapia de Intensidade Modulada/efeitos adversos , Reirradiação/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Área Sob a Curva , Carboplatina/administração & dosagem , Quimiorradioterapia/métodos , Fracionamento da Dose de Radiação , Fístula Esofágica/etiologia , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/patologia , Esofagite/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Paclitaxel/administração & dosagem , Pneumonite por Radiação/etiologia , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Reirradiação/métodos , Carga Tumoral
16.
Lab Med ; 51(2): e16-e19, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31622460

RESUMO

Myeloperoxidase (MPO) deficiency, one of the most common inherited phagocyte defects, and may exist as a transient phenomenon in combination with some clinical condition. Hematological analyzer ADVIA 2120i is used to identify the different types of leukocytes based on their size and staining properties, and by mean peroxidase index (MPXI). When MPO deficiency is present, neutrophils may be incorrectly counted as monocytes with lower MPXI values. We encountered a few cases of MPO deficiency with abnormally high monocytes counts resulting in pseudoneutropenia. These abnormal reports could lead to a mistaken diagnosis of severe neutropenia, which could result in unnecessary therapy. Manual differential count exhibited the normal differential count in every case. Every case yielded a markedly low MPXI value below -20. In conclusion, we suggest that MPO deficiency must be considered in patients especially when abnormally high monocyte counts combined with low MPXI values are observed.


Assuntos
Contagem de Leucócitos , Erros Inatos do Metabolismo/patologia , Monócitos/citologia , Neutropenia/etiologia , Neutrófilos/citologia , Peroxidase/deficiência , Adulto , Erros de Diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
17.
Chemotherapy ; 64(3): 155-162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31715597

RESUMO

Bendamustine is a cytostatic drug with a unique structure, combining the features of purine nucleoside analogs and alkylating agents. In patients with chronic lymphocytic leukemia (CLL) it is commonly used in combination with rituximab (BR protocol) both in the first-line as well as subsequent lines of therapy, and in clinical trials it is often combined with new targeted therapies. Therefore, the data on its real-life safety and efficacy are of clinical significance. As the Polish Lymphoma Research Group (PLRG), we retrospectively analyzed the efficacy and tolerability of bendamustine monotherapy in 96 patients with CLL. The median number of bendamustine cycles was 5, and 44 patients did not complete the planned 6 cycles (46%). Among the adverse events associated with the earlier termination of bendamustine treatment, infections were the most common (20.5%), followed by neutropenia (15.9%) and thrombocytopenia (15.9%). Dose reductions and/or delays occurred in 31% of treatment cycles (132 of 425) with neutropenia (17.9%) as the most frequent cause. Efficacy analysis showed an overall response rate of 88.2% with complete remission and partial remission achieved in 43.8 and 41.7% of patients, respectively. At the 24th month of follow-up, progression-free survival was 52% and overall survival was 69.7%. Bendamustine in monotherapy was found to be safe and efficacious, at least in terms of early response. Special attention should be paid to infectious complications, and especially that immune disorders are characteristic in the clinical course of CLL. Our observations suggest efforts must be made to ensure the proper timing and proper dose in the administration of the drug, and to avoid the premature termination of the treatment.


Assuntos
Cloridrato de Bendamustina/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Cloridrato de Bendamustina/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Neutropenia/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Trombocitopenia/etiologia , Resultado do Tratamento
18.
FP Essent ; 485: 11-16, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31613563

RESUMO

Leukopenia is a common finding in the outpatient setting. It typically occurs because of a significant reduction in neutrophils, which comprise 50% to 70% of circulating leukocytes. Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1,500/mcL. Neutropenia is classified by whether it is transient or chronic. Chronic neutropenia can be further described as extrinsic or intrinsic. Extrinsic causes are varied. Intrinsic causes can include impaired proliferation and maturation of myeloid progenitor cells in the bone marrow. Assessment of patients with neutropenia should be guided by the severity on presentation. The duration of leukopenia and the clinical status of the patient also should be considered. Some patients with neutropenia can develop life-threatening bacterial infections. In neutropenic patients, the risk of febrile neutropenia should be assessed systematically. Patients with febrile neutropenia should undergo treatment with antibiotics. Other treatments are aimed at management of the underlying cause of neutropenia.


Assuntos
Neutropenia , Humanos , Neutropenia/diagnóstico , Neutropenia/etiologia , Neutropenia/terapia , Neutrófilos
19.
S Afr Med J ; 109(8b): 40-45, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31662148

RESUMO

Human immunodeficiency virus (HIV) infection not only leads to a compromised immune system, but also disrupts normal haematopoiesis, resulting in the frequent manifestation of cytopenias (anaemia, thrombocytopenia and neutropenia). Although there is a definite association between the severity of cytopenia and HIV disease stage, this relationship is not always linear. For example, cytopenias such as thrombocytopenia may occur during early stages of infection. The aetiology of these haematological abnormalities is complex and multifactorial, including drug-induced impaired haematopoiesis, bone marrow suppression due to infiltration of infectious agents or malignant cells, HIV-induced impaired haematopoiesis, and several other factors. In this review, we describe the frequencies of anaemia, thrombocytopenia and neutropenia reported for HIV-infected, treatment-naïve cohorts studied in eastern and southern sub-Saharan African countries. We present a rational approach for the use of diagnostic tests during the workup of HIV-infected patients presenting with cytopenia, and discuss how HIV impacts on haematopoietic stem/progenitor cells (HSPCs) resulting in impaired haematopoiesis. Finally, we describe the direct and indirect effects of HIV on HSPCs which result in defective haematopoiesis leading to cytopenias.


Assuntos
Infecções por HIV/complicações , Hematopoese , Anemia/diagnóstico , Anemia/etiologia , Células-Tronco Hematopoéticas/citologia , Humanos , Neutropenia/diagnóstico , Neutropenia/etiologia , Células-Tronco/citologia , Trombocitopenia/diagnóstico , Trombocitopenia/etiologia
20.
BMC Infect Dis ; 19(1): 836, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31601195

RESUMO

BACKGROUND: Moraxella nonliquefaciens is a usually non-pathogenic biofilm-producing Gram-negative coccobacillus which may colonize the upper respiratory tract, rarely causing invasive disease. Although very rare, bloodstream infections caused by this organism have been described, showing often a fatal outcome. Here, we report the case of a pediatric cancer patient with bloodstream infection and sepsis due to M. nonliquefaciens showing full recovery after appropriate antibiotic treatment. CASE PRESENTATION: A three-year-old boy with stage IV neuroblastoma was admitted for high-dose chemotherapy with autologous stem cell rescue after standard neuroblastoma treatment. Despite receiving antimicrobial prophylaxis with trimethoprim/sulfamethoxazole, acyclovir and amphothericin B, the patient presented with fever of up to 39.5 °C and neutropenia. Besides a chemotherapy-related mucositis and an indwelling Broviac catheter (removed), no infection focus was identified on physical examination. Moraxella nonliquafaciens was identified in blood cultures. After antibiotic treatment and neutrophil recovery, the patient was fit for discharge. CONCLUSIONS: The case described highlights the importance of an otherwise non-pathogenic microorganism, especially in immunosupressed cancer patients. It should be kept in mind that, although very infrequently, Moraxella nonliquefaciens may cause bloodstream infections that can be successfully treated with prompt focus identification and antibiotic therapy.


Assuntos
Bacteriemia/diagnóstico , Moraxella/isolamento & purificação , Neoplasias/patologia , Sepse/diagnóstico , Antibacterianos/uso terapêutico , Antineoplásicos/uso terapêutico , Bacteriemia/complicações , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Pré-Escolar , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/diagnóstico , Neutropenia/etiologia , Sepse/etiologia , Sepse/microbiologia
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