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1.
N Engl J Med ; 384(19): 1810-1823, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33979489

RESUMO

BACKGROUND: Hairy-cell leukemia (HCL) is a CD20+ indolent B-cell cancer in which a BRAF V600E kinase-activating mutation plays a pathogenetic role. In clinical trials involving patients with refractory or relapsed HCL, the targeting of BRAF V600E with the oral BRAF inhibitor vemurafenib led to a response in 91% of the patients; 35% of the patients had a complete response. However, the median relapse-free survival was only 9 months after treatment was stopped. METHODS: In a phase 2, single-center, academic trial involving patients with refractory or relapsed HCL, we assessed the safety and efficacy of vemurafenib (960 mg, administered twice daily for 8 weeks) plus concurrent and sequential rituximab (375 mg per square meter of body-surface area, administered for 8 doses over a period of 18 weeks). The primary end point was a complete response at the end of planned treatment. RESULTS: Among the 30 enrolled patients with HCL, the median number of previous therapies was 3. A complete response was observed in 26 patients (87%) in the intention-to-treat population. All the patients who had HCL that had been refractory to chemotherapy (10 patients) or rituximab (5) and all those who had previously been treated with BRAF inhibitors (7) had a complete response. Thrombocytopenia resolved after a median of 2 weeks, and neutropenia after a median of 4 weeks. Of the 26 patients with a complete response, 17 (65%) were cleared of minimal residual disease (MRD). Progression-free survival among all 30 patients was 78% at a median follow-up of 37 months; relapse-free survival among the 26 patients with a response was 85% at a median follow-up of 34 months. In post hoc analyses, MRD negativity and no previous BRAF inhibitor treatment correlated with longer relapse-free survival. Toxic effects, mostly of grade 1 or 2, were those that had previously been noted for these agents. CONCLUSIONS: In this small study, a short, chemotherapy-free, nonmyelotoxic regimen of vemurafenib plus rituximab was associated with a durable complete response in most patients with refractory or relapsed HCL. (Funded by the European Research Council and others; HCL-PG03 EudraCT number, 2014-003046-27.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Rituximab/administração & dosagem , Vemurafenib/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/patologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Neutropenia/induzido quimicamente , Intervalo Livre de Progressão , Recidiva , Indução de Remissão , Rituximab/efeitos adversos , Trombocitopenia/induzido quimicamente , Vemurafenib/efeitos adversos
2.
Cell Stem Cell ; 28(5): 790-792, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33961760

RESUMO

In this issue of Cell Stem Cell, Daniel Bauer and colleagues investigate the pathogenesis of ELANE-associated severe congenital neutropenia (SCN) and describe two potentially universal gene correction strategies for autosomal dominant disorders (Rao et al., 2021). One exploits nonsense-mediated decay to prevent translation of the mutant allele. The other unexpectedly blocks translation by shortening the 3'-UTR.


Assuntos
Elastase de Leucócito , Neutropenia , Edição de Genes , Humanos , Elastase de Leucócito/genética , Mutação , Neutropenia/genética , Virulência
3.
J Med Case Rep ; 15(1): 273, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34039422

RESUMO

BACKGROUND: Felty syndrome is a rare manifestation of chronic rheumatoid arthritis in which patients develop extraarticular features of hepatosplenomegaly and neutropenia. The typical presentation of Felty syndrome is in Caucasians, females, and patients with long-standing rheumatoid arthritis of 10 or more years. This case report presents a patient with an early-onset and atypical demographic for Felty syndrome. CASE PRESENTATION: Our patient is a 28-year-old African American woman with past medical history of rheumatoid arthritis diagnosed in 2017, asthma, pneumonia, anemia, and mild intellectual disability who was admitted to inpatient care with fever, chills, and right ear pain for 7 days. The patient's mother, also her caregiver, brought the patient to the hospital after symptoms of fever and ear pain failed to improve. Our patient was diagnosed with sepsis secondary to pneumonia and urinary tract infection. She had been admitted twice in the past year, both times with a diagnosis of pneumonia. During this visit in September 2019, it was discovered that the patient had leukopenia and neutropenia. Bone marrow biopsy revealed increased immature mononuclear cells with left shift and rare mature neutrophils. During the hospital course, the patient was provisionally diagnosed with Felty syndrome and treated with adalimumab and hydroxychloroquine for her rheumatoid arthritis. Her sepsis secondary to pneumonia and urinary tract infection was treated with ceftriaxone and doxycycline, which was later switched to cefepime because of positive blood and urine cultures for Pseudomonas aeruginosa. She was discharged with stable vital signs and is continuing to control her rheumatoid arthritis with adalimumab. CONCLUSION: This case report details the clinical course of sepsis secondary to pneumonia and urinary tract infection in the setting of Felty syndrome. Our patient does not fit the conventional profile for presentation given her race, age, and the length of time following diagnosis of rheumatoid arthritis.


Assuntos
Artrite Reumatoide , Síndrome de Felty , Neutropenia , Adulto , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Síndrome de Felty/complicações , Síndrome de Felty/diagnóstico , Síndrome de Felty/tratamento farmacológico , Feminino , Humanos , Baço , Esplenomegalia
4.
BMJ Case Rep ; 14(5)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980567

RESUMO

A novel coronaravirus, identified as SARS-CoV-2, spread throughout the world in 2020. The COVID-19 pandemic has led to many discoveries and clinical manifestations. A young patient is presented with new, self-resolving neutropenia presenting weeks after a prolonged hospital stay for COVID-19 pneumonia. Workup included analysis for underlying infection, nutritional abnormalities, malignancy, medication and toxin exposure, all of which were negative. From 2020 to the present, few reports have described neutropenia associated with a recent COVID-19 infection. In particular, no reports have described a delayed presentation of neutropenia. The authors would like to propose that the significant inflammatory response associated with COVID-19 is likely what led to this patient's postviral neutropenia. Furthermore, in young healthy patients, bone marrow biopsy may be deferred and a watchful-waiting approach may be taken to assess for neutropenia resolution.


Assuntos
Neoplasias , Neutropenia , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Pandemias
6.
Cell Stem Cell ; 28(5): 906-922.e6, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33894142

RESUMO

Severe congenital neutropenia (CN) is a pre-leukemic bone marrow failure syndrome that can evolve to acute myeloid leukemia (AML). Mutations in CSF3R and RUNX1 are frequently observed in CN patients, although how they drive the transition from CN to AML (CN/AML) is unclear. Here we establish a model of stepwise leukemogenesis in CN/AML using CRISPR-Cas9 gene editing of CN patient-derived iPSCs. We identified BAALC upregulation and resultant phosphorylation of MK2a as a key leukemogenic event. BAALC deletion or treatment with CMPD1, a selective inhibitor of MK2a phosphorylation, blocked proliferation and induced differentiation of primary CN/AML blasts and CN/AML iPSC-derived hematopoietic stem and progenitor cells (HSPCs) without affecting healthy donor or CN iPSC-derived HSPCs. Beyond detailing a useful method for future investigation of stepwise leukemogenesis, this study suggests that targeting BAALC and/or MK2a phosphorylation may prevent leukemogenic transformation or eliminate AML blasts in CN/AML and RUNX1 mutant BAALC(hi) de novo AML.


Assuntos
Células-Tronco Pluripotentes Induzidas , Leucemia Mieloide Aguda , Proteínas de Neoplasias , Neutropenia , Síndrome Congênita de Insuficiência da Medula Óssea , Humanos , Leucemia Mieloide Aguda/genética , Mutação/genética , Proteínas de Neoplasias/genética , Neutropenia/congênito , Neutropenia/genética , Oncogenes
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(4): 375-380, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33840410

RESUMO

OBJECTIVE: To study the risk factors and treatment for neutropenia of late newborns (NLN). METHODS: Related clinical data were collected from the preterm infants and critically ill neonates who were admitted to the neonatal intensive care unit from July 2019 to January 2020. A total of 46 newborns with a blood absolute neutrophil count (ANC) of < 1.5×109/L for two consecutive times at weeks 2-4 after birth were enrolled as the NLN group. A total of 92 late newborns with a blood ANC of ≥ 1.5×109/L, matched at a ratio of 1:2, were enrolled as the control group. Possible risk factors associated with NLN and the treatment process were recorded. A logistic regression analysis was performed to identify the risk factors for NLN. RESULTS: Among the 46 neonates in the NLN group, 29 had a gestational age of < 32 weeks, 14 had a gestational age of 32-37 weeks, and 3 had a gestational age of > 37 weeks. There was no significant difference between the two groups in the incidence rates of gestational hypertension, premature rupture of membranes > 18 hours and intrauterine distress, 5-minute Apgar score, the duration of positive pressure ventilation, the incidence rate of early-onset sepsis, and the type of initially used antibiotics (P > 0.05). Compared with the control group, the NLN group had a higher incidence rate of late-onset sepsis and a longer duration of antibiotic use (P < 0.05). Late-onset sepsis and prolonged duration of antibiotic use were independent risk factors for NLN (P < 0.05). With the presence of late-onset sepsis, the risk of NLN was increased by 1.537 times in neonates, and the risk of NLN was increased by 76.9% for every 3-day increase in the duration of antibiotic use. The mean age at the diagnosis of NLN was (21±6) days for the 46 neonates in the NLN group. Thirteen neonates with NLN were administered with recombinant human granulocyte colony-stimulating factor (G-CSF, 10 µg/kg) once or twice. O the 13 neonates, 6 had an ANC of < 0.5×109/L and 7 had a gestational age of < 32 weeks or severe disease conditions. After treatment the ANC returned to > 1.0×109/L in the 13 neonates. No drug-related adverse reactions were found. After the diagnosis of NLN, 2 neonates developed sepsis, and the remaining 44 neonates did not develop any common purulent infections. CONCLUSIONS: The risk of NLN increases with the presence of late-onset sepsis and the increase in the duration of antibiotic use. NLN is generally a benign process. G-CSF appears to be safe and effective for NLN with severe disease conditions or severe reduction in ANC.


Assuntos
Neutropenia , Sepse , Fator Estimulador de Colônias de Granulócitos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Contagem de Leucócitos , Fatores de Risco
8.
Ann Hematol ; 100(6): 1509-1516, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33900450

RESUMO

Treatment outcomes of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) are far from satisfactory. Certain efficacy of ibrutinib has been observed in non-GCB subtype DLBCL patients. This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression. Combinational therapy (ibrutinib 560mg/day; venetoclax started 1 week later, oral dose increased from 100 to 400mg/day in 3 weeks) was conducted, and one cycle was 4 weeks. Both drugs were stopped when disease progress or serious adverse reactions appear. The primary end-point was overall response rate (ORR) at two cycles. From December 2018 to July 2020, a total of 13 patients were treated with the combined therapy. Among them, eleven (84.6%) patients previously received at least two treatment regimens, eight (61.5%) patients were C-myc and BCL2 double expression. The ORR at two cycles was 61.5%, with 3 (23.1%) patients achieved complete remission (CR) and 5 (38.4%) patients achieved partial remission (PR). The ORR at four cycles and six cycles was 53.8% and 46.2%, respectively. The median duration of response was 11 months (range, 1.5-13.6 months). The median progression-free survival and overall survival were 5.6 months (range, 0.4-15.6) and 11.3 months (range, 2.8-17.2), respectively. The most common adverse event was grade 1/2 neutropenia (53.8%), and nonhematologic toxicities included Grade1/2 diarrhea (46.2%) and elevated liver enzymes (30.8%). Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.


Assuntos
Adenina/análogos & derivados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Piperidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neutropenia/induzido quimicamente , Piperidinas/efeitos adversos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sulfonamidas/efeitos adversos , Resultado do Tratamento
9.
Arq Gastroenterol ; 58(1): 87-92, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33909803

RESUMO

BACKGROUND: Glycogen storage disease (GSD) type 1b is a multisystemic disease in which immune and infectious complications are present, in addition to the well-known metabolic manifestations of GSD. Treatment with granulocyte-colony stimulating factor (G-CSF) is often indicated in the management of neutropenia and inflammatory bowel disease. OBJECTIVE: To report on the demographics, genotype, clinical presentation, management, and complications of pediatric patients with glycogen storage disease type 1b (GSD 1b), with special attention to immune-related complications. METHODS: Retrospective case series of seven patients with GSD 1b diagnosed and followed at a tertiary university hospital in Brazil, from July/2000 until July/2016. RESULTS: Mean age at referral was fourteen months. Diagnosis of GSD 1b was based on clinical and laboratory findings and supported by genetic studies in five cases. All patients presented suffered from neutropenia, managed with G-CSF - specifically Filgrastim. Hospitalizations for infections were frequent. Two patients developed inflammatory bowel disease. Six patients remained alive, one died at age 14 years and 9 months. The mean age at the end of the follow-up was 11.5 years. Compliance to treatment was suboptimal: poor compliance to medications, starch and dietetic management of GSD were documented, and outpatient appointments were frequently missed. CONCLUSION: Managing GSD 1b is challenging not only for the chronic and multisystemic nature of this disease, but also for the additional demands related dietary restrictions, use of multiple medications and the need for frequent follow-up visits; furthermore in Brazil, the difficulties are increased in a scenario where we frequently care for patients with unfavorable socioeconomic status and with irregular supply of medications in the public health system.


Assuntos
Doença de Depósito de Glicogênio Tipo I , Neutropenia , Adolescente , Brasil , Criança , Doença de Depósito de Glicogênio Tipo I/complicações , Doença de Depósito de Glicogênio Tipo I/terapia , Fator Estimulador de Colônias de Granulócitos , Humanos , Estudos Retrospectivos
10.
Bull Cancer ; 108(5): 544-552, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-33820647

RESUMO

INTRODUCTION: The addition of palbociclib to endocrine therapy has been shown to improve progression free survival in hormone receptor positive metastatic breast cancer patients. This cyclin CDK4/6 inhibitor could expose patients to a grade 3-4 hematological toxicity, leading to treatment discontinuation or treatment interruption that is potentially associated with a lack of efficiency. The aim of this study was to identify predictive factors of severe early hematotoxicity (ESHT). METHODS: This retrospective cohort study included patients who started palbociclib in the Institut Sainte Catherine between December 1, 2016 and January 1, 2019 for the treatment of metastatic breast cancer. Individual data and hematological toxicity were collected from electronic medical records. ESHT was defined as the occurrence, during the first 3 cycles, of grade 4 or grade 3 hematological toxicity requiring palbociclib dose reduction. RESULTS: In total, 181 patients (180 females) were included; median age was 67 years. Forty-six patients (25.4%) experienced an ESHT. Predictive factors of ESHT in multivariate analysis were a performance status (PS) of 2 or more (P=0.024) and an history of radiotherapy of bone metastasis in the previous year (P=0.003). Before palbociclib initiation, a neutrophil count below 3.37g/L was predictive of ESHT with a sensibility of 76% and a specificity of 71%. CONCLUSIONS: ECOG PS, bone radiotherapy within the year and low baseline neutrophils count are associated with ESHT in palbociclib-treated metastatic breast cancer patients. These elements could be useful for a careful monitoring leading to adapted therapy.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Piperazinas/efeitos adversos , Piridinas/efeitos adversos , Trombocitopenia/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama Masculina/patologia , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Feminino , Fulvestranto/efeitos adversos , Fulvestranto/uso terapêutico , Humanos , Letrozol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neutropenia/induzido quimicamente , Piperazinas/uso terapêutico , Intervalo Livre de Progressão , Piridinas/uso terapêutico , Estudos Retrospectivos
11.
Oncol. (Guayaquil) ; 31(1): 75-85, Abril 30, 2021.
Artigo em Espanhol | LILACS | ID: biblio-1222727

RESUMO

Introducción: La neutropenia febril es una complicación que predispone a infecciones bacterianas de etiología diversa y aumenta la mortalidad en los pacientes con leucemia. El objetivo general del presente trabajo determinó la frecuencia de la etiología bacteriana, en los objetivos específicos se cuantificó en porcentaje los tipos de bacterias encontradas, se identificó la susceptibilidad y la resistencia antimicrobiana, además de sus infecciones, se estableció los factores de alto riesgo de mal pronóstico más frecuentes. Métodos: En el presente descriptivo de tipo transversal se revisaron historias clínicas del servicio de oncología clínica del Instituto Oncológico Nacional "Dr. Juan Tanca Marengo" Solca_Guayquil. El período estudio fue del 1ro de enero del 2013 al 31 de diciembre del 2014. El cálculo muestral fue probabilístico de 60 casos. Se incluyeron pacientes con leucemia en curso de quimioterapia y que evolucionaron con leucopenia febril, adicionalmente se incluyeron los pacientes con focos infecciosos evidentes y cultivos positivos. Las variables fueron demográficas características clínicas de la leucemia, estudio bacteriológico, tratamiento antibiótico y comorbilidades. Se utiliza estadística descriptiva. Resultados: Ingresaron al estudio 58 pacientes, fueron 30/58 mujeres (51%). La mayoría con edades de 17 a 20 años 15/58 casos (25.9%). 35/58 casos (60%) correspondieron a leucemias linfobásticas y 23/58 casos (40%) a miloides. El foco infeccioso más frecuentemente fue gastrointestinal 18 %(n=27), la piel y tejidos blandos con un 17 %(n=26). Se realizaron 98 cultivos, con el 52% de culti-vos positivos, 25 % BLEE, 4% BLAC. La etiología fue E. Coli 26% aislada de sangre. La sensibilidad fue 100 % amikacina, 100 %, imipenem ,100 meropenem, 100 % tigeciclina, 90 % piperazilina tazobactam, 18 %, cefepime, 50% clindamicina y 50% oxacilina. El máximo tiempo de neutropenia fue 30 días, con una mediana de neutrófilos 230 u/ul, con un promedio de 3 días de fiebre. Los factores de riesgo fueron 17% desnutrición ,15% hepatopatías %, 6% hipertensión y diabetes. Conclusiones: La etiología bacteriana más frecuente fue E. Coli. Existe una sensibilidad antibiótica baja para los gram negativos en todas las cefalosporinas de primera hasta cuarta generación en los antibiogramas del estudio. Hay un perfil de baja resistencia a los antibióticos carbapenémicos junto a amikacina con piperacilina tazobactam. La vancomicina y el linezolid no tienen resistencia bacteriana la presentación etológica para gram positivos, el más prevalente fue el estafilococo aureus meticilino resistente tipo BLAC.


Introduction: Febrile neutropenia is a complication that predisposes to bacterial infections of diverse etiology and increases mortality in patients with leukemia. The general objective of this work determined the frequency of bacterial etiology, in the specific objectives the types of bacteria found were quantified in percentage, susceptibility and antimicrobial resistance were identified, in addition to their infections, factors were established high risk of poor prognosis more frequent. Methods: In this descriptive cross-sectional type, clinical records of the clinical oncology service of the National Oncological Institute "Dr. Juan Tanca Marengo "Solca_Guayquil. The study period was from January 1, 2013 to December 31, 2014. The sample calculation was probabilistic of 60 cases. Patients with leukemia undergoing chemotherapy and who evolved with febrile leukopenia were included, additionally patients with obvious infectious foci and positive cultures were included. The variables were demographic, clinical characteristics of the leukemia, bacteriological study, antibiotic treatment, and comorbidities. Descriptive statistics are used. Results: 58 patients entered the study, 30/58 were women (51%). The majority aged 17 to 20 years 15/58 cases (25.9%). 35/58 cases (60%) corresponded to lymphoblastic leukemias and 23/58 cases (40%) to myloids. The most frequent infectious focus was gastrointestinal 18% (n = 27), skin and soft tissues with 17% (n = 26). 98 cultures were performed, with 52% positive cultures, 25% ESBL, 4% BLAC. The etiology was E. Coli 26% isolated from blood. The sensitivity was 100% amika-cin, 100%, imipenem, 100 meropenem, 100% tigecycline, 90% tazobactam piperazilin, 18%, ce-fepime, 50% clindamycin, and 50% oxacillin. The maximum time of neutropenia was 30 days, with a neutrophil average of 230 u / ul, with an average of 3 days of fever. The risk factors were 17% malnutrition, 15% liver disease, 6% hypertension and diabetes. Conclusions: The most frequent bacterial etiology was E. Coli. There is a low antibiotic sensitivity for gram negatives in all first through fourth generation cephalosporins in the study antibiograms. There is a profile of low resistance to carbapenemic antibiotics together with amikacin with piperacillin tazobactam. Vancomycin and linezolid do not have bacterial resistance in the ethological presentation for gram positives, the most prevalent was methicillin-resistant staphylococcus aureus BLAC type.


Assuntos
Leucemia , Neutropenia Febril Induzida por Quimioterapia , Hemocultura , Neutropenia Febril , Neutropenia
12.
BMJ Case Rep ; 14(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33753395

RESUMO

A 61-year-old man was transferred to our facility from an outside hospital due to refractory neutropaenia of unknown aetiology. The patient presented to the referring hospital with a 5-day history of worsening diarrhoea and abdominal pain. Initial lab results at presentation showed severe neutropaenia with an absolute neutrophil count of 0. Investigations included a bone marrow biopsy which showed slightly hypocellular marrow with near absence of granulocytic precursors. A CT without contrast showed evidence of chronic pancreatitis and acute colitis. The patient's neutropaenia persisted despite granulocyte colony-stimulating factor therapy. The patient was, thus, transferred to our facility for a higher level of care. At our facility, the patient had rapid correction of neutropaenia after discontinuation of pancrelipase therapy. The patient's abdominal pain and diarrhoea also improved while off pancrelipase. Neutropaenia has completely resolved 6 weeks after discharge without any further therapy.


Assuntos
Neutropenia , Pancrelipase , Fator Estimulador de Colônias de Granulócitos , Granulócitos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente
13.
Sci Rep ; 11(1): 4814, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649382

RESUMO

Corticosteroids, anti-CD20 agents, immunotherapies, and cytotoxic chemotherapy are commonly used in the treatment of patients with cancer. It is unclear how these agents affect patients with cancer who are infected with SARS-CoV-2. We retrospectively investigated associations between SARS-CoV-2-associated respiratory failure or death with receipt of the aforementioned medications and with pre-COVID-19 neutropenia. The study included all cancer patients diagnosed with SARS-CoV-2 at Memorial Sloan Kettering Cancer Center until June 2, 2020 (N = 820). We controlled for cancer-related characteristics known to predispose to worse COVID-19 as well as level of respiratory support during corticosteroid administration. Corticosteroid administration was associated with worse outcomes prior to use of supplemental oxygen; no statistically significant difference was observed in sicker cohorts. In patients with metastatic thoracic cancer, 9 of 25 (36%) and 10 of 31 (32%) had respiratory failure or death among those who did and did not receive immunotherapy, respectively. Seven of 23 (30%) and 52 of 187 (28%) patients with hematologic cancer had respiratory failure or death among those who did and did not receive anti-CD20 therapy, respectively. Chemotherapy itself was not associated with worse outcomes, but pre-COVID-19 neutropenia was associated with worse COVID-19 course. Relative prevalence of chemotherapy-associated neutropenia in previous studies may account for different conclusions regarding the risks of chemotherapy in patients with COVID-19. In the absence of prospective studies and evidence-based guidelines, our data may aid providers looking to assess the risks and benefits of these agents in caring for cancer patients in the COVID-19 era.


Assuntos
Corticosteroides/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Neoplasias Hematológicas , Fatores Imunológicos/administração & dosagem , Idoso , /mortalidade , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/tratamento farmacológico , Neutropenia/mortalidade , Insuficiência Respiratória , Estudos Retrospectivos
14.
J Psychiatry Neurosci ; 46(2): E232-E237, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33703870

RESUMO

Background: Monitoring of white cell counts during clozapine treatment leads to cessation of therapy if levels fall below predetermined values. Reductions in white cell counts, driven by lower levels of lymphocytes, have been observed with coronavirus disease 2019 (COVID-19). Neutropenia during COVID-19 has not been reported. We present data for 56 patients who were taking clozapine and had COVID-19. Methods: We included patients who were taking clozapine at the time they tested positive for COVID-19. We compared absolute neutrophil counts, lymphocyte counts and white cell counts between baseline and the first week of infection, and baseline and the second week of infection. Results: We observed reductions in absolute neutrophil counts (p = 0.005), lymphocyte counts (p = 0.003) and white cell counts (p < 0.001) between baseline and the first 7 days of COVID-19. All cell counts had returned to baseline levels by days 8 to 14. Six patients experienced neutropenia (absolute neutrophil counts < 2.0 × 109/L) and of those, 4 underwent mandatory cessation of clozapine. For 3 patients, clozapine treatment had been established for more than 6 months with no previous neutropenia, neutrophil levels returned to baseline within 2 weeks and no further neutropenia was observed on restarting treatment. Limitations: This was a retrospective chart review; larger cohorts are required. Clozapine plasma levels were largely not measured by clinicians. Conclusion: These data strongly suggest that mild neutropenia in the acute phase of COVID-19 in patients who are well established on clozapine is more likely to be a consequence of the virus than of clozapine treatment.


Assuntos
Antipsicóticos/efeitos adversos , Clozapina/efeitos adversos , Neutropenia/etiologia , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Feminino , Humanos , Contagem de Leucócitos , Leucopenia/etiologia , Contagem de Linfócitos , Linfopenia/etiologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutrófilos , Estudos Retrospectivos , Adulto Jovem
15.
A A Pract ; 15(4): e01432, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33783367

RESUMO

The role of concurrent illness in coronavirus disease 2019 (COVID-19) is unknown. Patients with leukemia may display altered thromboinflammatory responses. We report a 53-year-old man presenting with acute leukemia and COVID-19 who developed thrombotic complications and acute respiratory distress syndrome. Multiple analyses, including rotational thromboelastometry and flow cytometry on blood and bronchoalveolar lavage, are reported to characterize coagulation and immune profiles. The patient developed chemotherapy-induced neutropenia that may have protected his lungs from granulocyte-driven hyperinflammatory acute lung injury. However, neutropenia also alters viral clearing, potentially enabling ongoing viral propagation. This case depicts a precarious equilibrium between leukemia and COVID-19.


Assuntos
Lesão Pulmonar Aguda/complicações , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/patologia , /patologia , Leucemia Mieloide Aguda/complicações , Lesão Pulmonar Aguda/diagnóstico , Lesão Pulmonar Aguda/patologia , Transtornos da Coagulação Sanguínea/diagnóstico , Lavagem Broncoalveolar , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/complicações , Neutropenia/diagnóstico , Neutropenia/patologia , Tromboelastografia , Fatores de Virulência
16.
BMJ Case Rep ; 14(3)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653834

RESUMO

Neutropenic enterocolitis (NEC) is a life-threatening bowel condition, usually resulting from chemotherapy, with a mortality rate thought to be as high as 50%. Markers of poor prognosis include gastrointestinal perforation and bowel wall thickness radiologically detected to be greater than 10 mm. NEC is associated with severe neutropenia and predominantly affects the large bowel; however, we present a case of severe NEC with oesophageal perforation requiring transfer to a specialist upper gastrointestinal unit for corrective stenting. Despite initial bowel wall thickness of 20 mm in the ascending colon, two discrete episodes of bowel perforation and an inpatient stay totalling 89 days, the patient was discharged with full independence, a good quality of life and a plan for curative mastectomy plus axillary clearance.


Assuntos
Neoplasias da Mama , Enterocolite Neutropênica , Neutropenia , Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Enterocolite Neutropênica/induzido quimicamente , Enterocolite Neutropênica/diagnóstico por imagem , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Qualidade de Vida
17.
Int J Hematol ; 113(5): 735-743, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33587282

RESUMO

Quality of life (QOL) and patient-reported outcomes (PROs) assessments in immunodeficiency patients, including those with chronic severe neutropenia conditions, are imperative to determining modifiable health-related features to optimize care. We present the largest study to date of QOL in those with chronic severe neutropenia conditions with further evaluation of patient provider satisfaction and patient-reported outcome measures. Subjects completed electronic surveys assessing QOL, PROs, and patient provider satisfaction. There is a significantly negative impact of a chronic severe neutropenia disorder on QOL, fatigue, physical function, cognitive function and pain in adult patients when compared to controls. Children with a chronic neutropenia condition had comparable QOL to controls, but reported fewer depressive symptoms, improved mobility, and stronger self-reported peer relationships. Adults had worse scores for QOL, depression and fatigue when compared to children. Adult and pediatric chronic severe neutropenia patients or their caregivers felt that their medical provider was compassionate, trustworthy, and accessible. However, less than 50% of adult patients agreed their clinician had excellent expertise in white blood cell disorders. Chronic neutropenia complexly affect QOL and PROs. An analysis of these parameters allows for targeted interventions to improve patient psychosocial, physical and neurocognitive health.


Assuntos
Neutropenia , Qualidade de Vida , Adulto , Criança , Depressão/etiologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Neutropenia/complicações , Neutropenia/psicologia , Medidas de Resultados Relatados pelo Paciente
19.
Blood Adv ; 5(3): 775-786, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560392

RESUMO

Mutations in ELANE cause severe congenital neutropenia (SCN), but how they affect neutrophil production and contribute to leukemia predisposition is unknown. Neutropenia is alleviated by CSF3 (granulocyte colony-stimulating factor) therapy in most cases, but dose requirements vary between patients. Here, we show that CD34+CD45+ hematopoietic progenitor cells (HPCs) derived from induced pluripotent stem cell lines from patients with SCN that have mutations in ELANE (n = 2) or HAX1 (n = 1) display elevated levels of reactive oxygen species (ROS) relative to normal iPSC-derived HPCs. In patients with ELANE mutations causing misfolding of the neutrophil elastase (NE) protein, HPCs contained elevated numbers of promyelocyte leukemia protein nuclear bodies, a hallmark of acute oxidative stress. This was confirmed in primary bone marrow cells from 3 additional patients with ELANE-mutant SCN. Apart from responding to elevated ROS levels, PML controlled the metabolic state of these ELANE-mutant HPCs as well as the expression of ELANE, suggestive of a feed-forward mechanism of disease development. Both PML deletion and correction of the ELANE mutation restored CSF3 responses of these ELANE-mutant HPCs. These findings suggest that PML plays a crucial role in the disease course of ELANE-SCN characterized by NE misfolding, with potential implications for CSF3 therapy.


Assuntos
Neutropenia , Proteínas Adaptadoras de Transdução de Sinal , Síndrome Congênita de Insuficiência da Medula Óssea , Fator Estimulador de Colônias de Granulócitos , Humanos , Mutação , Neutropenia/congênito , Neutropenia/genética
20.
Expert Opin Pharmacother ; 22(7): 857-865, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33579166

RESUMO

Introduction: Severe neutropenia and infections are potentially life-threatening complications of cytotoxic antineoplastic therapies and often require hospitalization with a severe economic impact. Furthermore, hematological toxicity frequently results in chemotherapy dose reductions and delays that could interfere with disease control.Areas covered: This review provides an overview of granulocyte colony-stimulating factors (G-CSFs) including pegylated molecules, as well as more recent biosimilar G-CSFs, focusing on the toxicity, pharmacokinetics, and efficacy of these compounds.Expert opinion: The administration of hematopoietic growth factors in primary and secondary prophylaxis of neutropenia is a standard supportive care measure. Recently, several biosimilars have been developed. The market for biosimilar agents seems to be increasing over time thanks to their similar effectiveness and safety, compared with their originators, but lower costs.


Assuntos
Medicamentos Biossimilares , Neoplasias , Neutropenia , Filgrastim , Fator Estimulador de Colônias de Granulócitos , Humanos , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Polietilenoglicóis , Proteínas Recombinantes
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