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1.
BMC Cancer ; 22(1): 349, 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35361149

RESUMO

BACKGROUND: The prognosis of patients with relapsed Ewing sarcoma is poor. In this study, we aimed to pooled-analyze the efficacy and safety of the combination of irinotecan and temozolomide in treating patients with relapsed Ewing sarcoma. METHODS: PubMed, Cochrane CENTRAL, Web of Science, and EMBASE were systematically searched on September 27, 2021. The primary outcomes were rates of objective response and disease control, and the secondary outcomes were toxicities. RESULTS: Six retrospective studies with 184 patients were enrolled in the analysis. The median age ranged from 14 to 21. The integrated rates were 44% (95% confidence interval [CI] 31-58) for objective response and 66% (55-77) for disease control. Grade 3-4 neutropenia, thrombocytopenia, and diarrhea occurred in 8% (3-16), 7% (3-11), and 8% (5-10) of chemotherapeutic cycles, respectively. 18% (7-32) and 6% (2-11) of patients suffered grade 3-4 neutropenia and thrombocytopenia after irinotecan plus temozolomide treatment. CONCLUSION: Irinotecan plus temozolomide combination chemotherapy showed antitumor activity and an acceptable safety profile in patients with relapsed Ewing sarcoma. More future prospective studies are needed to confirm the retrospective results.


Assuntos
Neutropenia , Sarcoma de Ewing , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina , Dacarbazina/efeitos adversos , Humanos , Irinotecano/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos Retrospectivos , Sarcoma de Ewing/tratamento farmacológico , Temozolomida/uso terapêutico
2.
J Hematol Oncol ; 15(1): 103, 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35922861

RESUMO

Patients with higher-risk myelodysplastic syndromes (MDS) refractory to hypomethylating agents (HMAs) have limited therapeutic options and an expected overall survival (OS) of 3-5 months. Eltanexor is an investigational oral selective inhibitor of nuclear export with low central nervous system penetrance and an acceptable tolerability profile. Preclinical studies suggest that myeloid malignancies are sensitive to nuclear export inhibition. Eltanexor exhibited efficacy in hematologic models, supporting exploration in a clinical trial. This phase 1/2 study (NCT02649790) assessed single-agent activity of eltanexor in patients with higher-risk MDS and 5-19% myeloblasts. Two starting doses of eltanexor were evaluated: 20 mg (n = 15), 10 mg (n = 5), both administered on days 1-5 each week of a 28-day cycle. Twenty patients with primary HMA-refractory MDS, with a median age of 77 years (range 62-89), and a median of two prior treatment regimens (range 1-4) were enrolled. Of these, 15 were evaluated for efficacy and 20 for safety. The overall response rate (ORR) was 53.3%, with seven patients (46.7%) achieving marrow complete remission (mCR) and one additional patient achieving hematologic improvement (HI). In the 10 mg group, three patients (60%) reached mCR and two (40%) stable disease (SD), while for 20 mg, four patients (40%) had mCR and two (20%) SD. A total of three patients (20%) had HI and became transfusion independent ≥ 8 weeks. Median OS for the efficacy-evaluable patients (n = 15) was 9.86 months (7.98, NE). Overall, the most frequently reported treatment-related adverse events were nausea (45%), diarrhea (35%), decreased appetite (35%), fatigue and neutropenia (both 30%). Single-agent oral eltanexor was active, safe, and well tolerated in patients with higher-risk, primary HMA-refractory MDS.


Assuntos
Antineoplásicos , Síndromes Mielodisplásicas , Neutropenia , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Humanos , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Neutropenia/induzido quimicamente , Resultado do Tratamento
3.
Rinsho Ketsueki ; 63(7): 753-758, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35922943

RESUMO

An 83-year-old man with chronic obstructive pulmonary disease, hypothyroidism, and osteoporosis developed neutropenia. He was diagnosed with agranulocytosis based on suppression and maturation arrest of myeloid series in the bone marrow. All of his prescriptions were stopped, and he was given granulocyte colony-stimulating factor because he was suspected to have drug-induced agranulocytosis. His neutropenia improved for a while, but it returned a month later. Serum soluble interleukin-2 receptor levels were elevated in his blood, and an abdominal computed tomography scan revealed splenomegaly with no lymph node enlargement. However, due to his old age, a splenectomy was not performed, and no definitive diagnosis was given. He received rituximab therapy after being considered for splenic marginal zone lymphoma or autoimmune neutropenia. His splenomegaly improved, but his neutropenia did not. He was then given ciclosporin, which resulted in a complete response. Because of the presence of large granular lymphocytes in the peripheral blood and bone marrow but no T-cell receptor gene rearrangement, the case was defined as chronic idiopathic neutropenia with activated T cells.


Assuntos
Ciclosporina , Neutropenia , Idoso , Idoso de 80 Anos ou mais , Ciclosporina/uso terapêutico , Fator Estimulador de Colônias de Granulócitos , Humanos , Masculino , Neutropenia/tratamento farmacológico , Esplenectomia , Esplenomegalia
4.
Biomed Res Int ; 2022: 4727407, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898681

RESUMO

Evidence for neoadjuvant chemotherapy combined with targeted therapy for locally advanced esophageal squamous cancer (ESCC) is inadequate. We conducted a single-arm phase II trial to evaluate the efficacy and safety of apatinib combined with taxol and cisplatin (ATP) for locally advanced ESCC. All patients were cT3-4aN0-3 M0 (IIIb-IVa) stage, which were confirmed by histopathology. Apatinib was taken orally (425 mg/d) for two cycles, followed by one cycle of rest. Taxol was administered at 135 mg/m2 intravenously on day 1, and cisplatin was administered at 20 mg/m2 intravenously on day 1 to day 3. Radical ESCC resection was performed 4 weeks after ATP. The primary endpoint was pathological response rate (pCR). Secondary endpoints were pathologic response rate (MPR), disease-free survival (DFS), overall survival (OS), R0 resection rate, and safety profile. This trial was registered. We evaluated 41 patients for screening from Oct 2018 to July 2020, of whom 39 were enrolled in the study, with a median age of 65 years (range 49-75 years), and 29 (74.4%) were male. Among the 39 patients, 1 was considered unresectable by the multidisciplinary team due to tumor progression, and 38 patients underwent surgery eventually. The median follow-up was 22 months (range 5-29 months), and the follow-up rate was 100%. The 1-year and 2-year OS was 95% and 95%, and the 1-year and 2-year DFS was 85% and 82%, respectively. Thirty-eight (97.3%) successfully underwent R0 resection. Of the 38 evaluable patients, 9 (23.6%) were pCR, and 15 (39.5%) were MPR. The most common ATP-related AEs were nausea (76.9%), leucopenia (53.8%), neutropenia (51.2%) and vomit (51.2%), anemia (41.0%), and hypertension (25.6%). The most frequent grade 3-4 events included leucopenia (15.3%), neutropenia (15.3%), nausea (12.8%), vomit (12.8%), and hypertension (10.2%). No treatment-related death occurred. Neoadjuvant apatinib combined with taxol and cisplatin for locally advanced ESCC showed favorable activity and manageable safety.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Hipertensão , Neutropenia , Trifosfato de Adenosina , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/efeitos adversos , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Náusea/tratamento farmacológico , Terapia Neoadjuvante , Neutropenia/tratamento farmacológico , Paclitaxel/efeitos adversos , Piridinas
5.
Oncology ; 100(8): 449-459, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35816996

RESUMO

INTRODUCTION: This retrospective study investigated the efficacy and safety of nano-liposomal irinotecan (nal-IRI) plus 5-fluorouracil/L-leucovorin (5-FU/l-LV) treatment in the second-line or later setting for advanced pancreatic cancer under real-world conditions. METHODS: Between June 2020 and September 2021, a total of 44 patients with unresectable advanced pancreatic cancer treated with nal-IRI + 5-FU/l-LV in our affiliated hospitals were included. The prognosis, predictive factors (including systemic inflammation-based prognostic indicators), and adverse events were investigated. RESULTS: The median age was 68 (interquartile range 62-73) years old, and 22 patients (50.0%) were male. Concerning tumor factors, 9 patients (20.5%) had local advanced disease and 35 patients (79.5%) had metastases. Twenty-five of the 44 patients were receiving second-line treatment, and 19 were receiving third-line or later treatment. The median overall survival (OS) and progression-free survival were 9.0 (range, 0.7-15.4) months and 4.4 (range, 0.6-15.4) months, respectively. The overall response rate was 5.3%. The disease control rate was 44.7%. Patients with a neutrophil-to-lymphocyte ratio of ≥2.7 had a significant risk of a poor OS (HR = 0.275, p = 0.017). Adverse events were manageable, although gastrointestinal symptoms and neutropenia were observed. The most common grade ≥3 adverse event was neutropenia, which was reported in 20% of patients. CONCLUSIONS: Nal-IRI + 5-FU/l-LV therapy was considered to be a useful regimen as second-line or later treatment for unresectable advanced pancreatic cancer, even in clinical practice.


Assuntos
Neutropenia , Neoplasias Pancreáticas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Feminino , Fluoruracila , Humanos , Irinotecano/efeitos adversos , Leucovorina , Lipossomos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos
7.
Assist Inferm Ric ; 41(2): 94-99, 2022.
Artigo em Italiano | MEDLINE | ID: mdl-35856309

RESUMO

. A fever in a neutropenic patient during chemotherapy: case report with questions. Over the next 3 issues, we will publish a series of updates on some of the oncological emergencies. The updates are published in the form of a case, with multiple-choice questions to assess knowledge, a brief discussion of the answer, and the reference literature, to further explore the topic. The first case involves the management of febrile neutropenia.


Assuntos
Neoplasias , Neutropenia , Febre/induzido quimicamente , Febre/complicações , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neutropenia/induzido quimicamente
8.
Sci Rep ; 12(1): 11341, 2022 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35790790

RESUMO

Cholangiocarcinoma (CCA) is an aggressive malignancy arising from the damaged epithelial cells of the biliary tract. Previous studies have reported that the multi-potent mesenchymal stem cells (MSCs) activate a series of tumor signaling pathways by releasing several cytokines to influence tumor cell development. However, the roles and mechanisms of human chorion-derived MSCs (CH-MSCs) in cholangiocarcinoma progression have not been fully addressed. This present study aims to examine the effects of conditioned media derived from CH-MSCs (CH-CM) on CCA cell lines and investigate the respective underlying mechanism of action. For this purpose, MSCs were isolated from chorion tissue, and three cholangiocarcinoma cell lines, namely KKU100, KKU213A, and KKU213B, were used. MTT assay, annexin V/PI analysis, and JC-1 staining were used to assess the effects of CH-CM on proliferation and apoptosis of CCA cells, respectively. Moreover, the effect of CH-CM on caspase-dependent apoptotic pathways was also evaluated. The western blotting assay was also used for measuring the expression of JAK2/STAT3 signaling pathway-associated proteins. The results showed that CH-CM suppressed proliferation and promoted apoptosis of CCA cell lines. CH-CM treatment-induced loss of mitochondrial membrane potential (∆Ψm) in CCA cell lines. The factors presented in the CH-CM also inhibited JAK2/STAT3 signaling, reduced the expression of BCL-2, and increased BAX expression in CCA cells. In conclusion, our study suggests that the CH-CM has a potent anti-cancer effect on cholangiocarcinoma cells and thus provides opportunities for use in alternative cell therapy or in combination with a conventional chemotherapeutic drug to increase the efficiency of CCA treatment.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Células-Tronco Mesenquimais , Apoptose , Ductos Biliares Intra-Hepáticos , Linhagem Celular , Córion , Humanos , Fatores Imunológicos , Janus Quinase 2 , Neutropenia , Fator de Transcrição STAT3 , Transdução de Sinais
9.
J Int Med Res ; 50(7): 3000605221110697, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35822291

RESUMO

OBJECTIVE: The UGT1A1*28 polymorphism reduces UGT1A1 enzymatic activity, which may increase the risk of severe toxicity in patients who receive standard-dose irinotecan, such as severe neutropenia and diarrhea. This real-world study assessed the optimal irinotecan dose in terms of efficacy and toxicity in metastatic colorectal cancer (mCRC) patients homozygous for the UGT1A1*28 polymorphism and receiving FOLFIRI plus bevacizumab or cetuximab as first-line therapy. METHODS: We analyzed toxicity and treatment outcomes in seven mCRC patients who were homozygous for UGT1A1*28 and received FOLFIRI plus bevacizumab or cetuximab, with an initial irinotecan dose of 120 mg/m2. RESULTS: Six of the seven patients tolerated 120 mg/m2 irinotecan without requiring dose reductions in subsequent cycles. The overall response and disease control rates were 43.0% (3/7) and 71.4% (5/7), respectively. The median progression-free survival and overall survival were 11.0 and 33.0 months, respectively. Only one severe adverse event, grade III neutropenia (2.5%), was observed. CONCLUSIONS: mCRC patients homozygous for the UGT1A1*28 allele can tolerate irinotecan at an initial dose of 120 mg/m2 with favorable oncological outcomes and toxicity profiles. Further prospective studies are warranted to optimize irinotecan-based chemotherapy in these patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Glucuronosiltransferase , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Cetuximab/administração & dosagem , Cetuximab/efeitos adversos , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Glucuronosiltransferase/genética , Glucuronosiltransferase/metabolismo , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/genética , Polimorfismo Genético
10.
Iran J Allergy Asthma Immunol ; 21(3): 344-354, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35822684

RESUMO

Neutropenia congenita grave (SCN) is a rare disease with a genetically and clinically heterogeneous nature, usually diagnosed in childhood, with an elevated risk of infections such as otitis, skin infections, pneumonia, deep abscesses, and septicemia. Patients with SCN also have an increased risk of leukemia, and mutations in the ELANE and the HAX1 genes have been observed in those patients. This study was conducted to genetically screen six Iranian families with SCN who have at least one affected person. In the first step, all exons and intron boundaries of ELANE and HAX1 genes were sequenced in probands. Cases with no pathogenic mutations were tested through whole-exome sequencing (WES). Analysis showed five different variants in ELANE (c.377 C>T), HAX1 (c.130_131 insA), HYOU1 (c.69 G>C and c.2744 G>A) and SHOC2 (c.4 A>G) genes in four families. We found that two out of six families had mutations in ELANE and HAX1 genes. Moreover, we found two novel mutations at the HYOU1 gene that had not previously been reported, as well as a pathogenic mutation at SHOC2 with multiple phenotypes, that will contribute to determining the genetic basis for SCN. Our study revealed that WES could help diagnose SCN, improve the classification of neutropenia, and rule out other immunodeficiencies such as autoimmune neutropenia, primary immunodeficiency diseases, and inherited bone marrow failure syndromes.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Síndrome Congênita de Insuficiência da Medula Óssea , Peptídeos e Proteínas de Sinalização Intracelular , Elastase de Leucócito , Neutropenia , Proteínas Adaptadoras de Transdução de Sinal/genética , Síndrome Congênita de Insuficiência da Medula Óssea/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Irã (Geográfico)/epidemiologia , Elastase de Leucócito/genética , Neutropenia/congênito , Neutropenia/diagnóstico , Neutropenia/genética
11.
BMJ Case Rep ; 15(7)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35793843

RESUMO

Acute colonic pseudo-obstruction, also known as Ogilvie's syndrome, is a rare condition involving acute large bowel dilatation without mechanical obstruction. Management begins with conservative treatment and may include pharmacological therapy, colonoscopic decompression and surgery. Timely resolution is important due to the increased risk of bowel perforation and ischaemia associated with colonic dilatation. However, conditions such as neutropenia that place patients at an elevated risk of infection may limit treatment options. We report a case of acute colonic pseudo-obstruction in a neutropenic elderly man resistant to conservative measures and neostigmine and discuss the additional management considerations in an immunocompromised patient.


Assuntos
Pseudo-Obstrução do Colo , Neutropenia , Idoso , Pseudo-Obstrução do Colo/complicações , Pseudo-Obstrução do Colo/terapia , Colonoscópios , Humanos , Masculino , Neostigmina/uso terapêutico
13.
Biomedica ; 42(2): 224-233, 2022 06 01.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-35867916

RESUMO

Introduction: Chagas disease is an endemic parasitic infection in Latin America transmitted by triatomines. It is associated with risk factors such as poverty and rurality. After acute infection, a third of patients will present target organ involvement (heart, digestive tract, central nervous system). The remaining two thirds remain asymptomatic throughout their life. Pharmacological immunosuppression breaks the balance between the immune system and the parasite, favoring its reactivation. Clinical case: We present the case of a 58-year-old man from a Colombian rural area with a diagnosis of multiple myeloma refractory to the first line of treatment who required a new chemotherapy scheme and consolidation with autologous stem cell transplant. During the post-transplant period, he suffered from febrile neutropenia. Initial microbiological studies were negative but the peripheral blood smear evidenced trypomastigotes in blood. With a diagnosis of acute Chagas disease in a post-transplant patient, benznidazole was started. The evolution of the patient was satisfactory. Conclusions: Positive serology prior to transplantation makes it necessary to rule out reactivation of the pathology in the setting of febrile neutropenia. More studies are required to determine tools for estimating the probability of reactivation of the disease and defining the best cost-risk-benefit relation for the prophylactic therapy.


Introducción. La enfermedad de Chagas es una parasitosis endémica en Latinoamérica transmitida por triatominos. Está asociada a factores de riesgo como la pobreza y la ruralidad. Después de la infección aguda, un tercio de los pacientes presenta compromiso del corazón, el aparato digestivo o el sistema nervioso central, en tanto que los dos tercios restantes no presentan este tipo de compromiso secundario. La inmunosupresión farmacológica rompe el equilibrio entre el sistema inmunitario y el parásito, lo cual favorece su reactivación. Caso clínico. Se presenta el caso de un hombre de 58 años procedente de un área rural colombiana, con diagnóstico de mieloma múltiple resistente a los fármacos de primera línea de tratamiento, que requirió un nuevo esquema de quimioterapia y consolidación con trasplante autólogo de células madre. Después del trasplante, presentó neutropenia febril. Los estudios microbiológicos iniciales fueron negativos. En el frotis de sangre periférica, se demostraron tripomastigotes y se diagnosticó enfermedad de Chagas aguda posterior al trasplante. Se inició el tratamiento con benznidazol. La evolución del paciente fue satisfactoria. Conclusiones. La serología positiva para Chagas previa a un trasplante obliga a descartar la reactivación de la enfermedad en caso de neutropenia febril. Se requieren más estudios para determinar las herramientas que permitan estimar la probabilidad de reactivación de la enfermedad y decidir sobre la mejor opción de relación entre costo, riesgo y beneficio de la terapia profiláctica.


Assuntos
Neutropenia , Humanos , Estudos Retrospectivos
14.
J Int Med Res ; 50(7): 3000605221109392, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35861236

RESUMO

OBJECTIVES: Early detection of coronavirus disease 2019 (COVID-19) is crucial for patients and public health to ensure pandemic control. We aimed to correlate clinical and laboratory data of patients with COVID-19 and their polymerase chain reaction (PCR) results and to assess the accuracy of a deep learning model in diagnosing COVID-19. METHODS: This was a retrospective study using an anonymized dataset of patients with suspected COVID-19. Only patients with a complete dataset were included (n = 440). A deep analytics framework and dual-modal approach for PCR-based classification was used, integrating symptoms and laboratory-based modalities. RESULTS: Participants with loss of smell or taste were two times more likely to have positive PCR results (odds ratio [OR] 1.86). Participants with neutropenia, high serum ferritin, or monocytosis were three, four, and five times more likely to have positive PCR results (OR 2.69, 4.18, 5.42, respectively). The rate of accuracy achieved using the deep learning framework was 78%, with sensitivity of 83.9% and specificity of 71.4%. CONCLUSION: Loss of smell or taste, neutropenia, monocytosis, and high serum ferritin should be routinely assessed with suspected COVID-19 infection. The use of deep learning for diagnosis is a promising tool that can be implemented in the primary care setting.


Assuntos
COVID-19 , Aprendizado Profundo , Neutropenia , Anosmia , COVID-19/diagnóstico , Ferritinas , Hospitais Universitários , Humanos , Estudos Retrospectivos , SARS-CoV-2
15.
Cochrane Database Syst Rev ; 7: CD008766, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35866378

RESUMO

BACKGROUND: Ovarian cancer is the seventh most frequent cancer diagnosis worldwide, and the eighth leading cause of cancer mortality. Epithelial ovarian cancer is the most common kind, accounting for 90% of cases. First-line therapy for women with epithelial ovarian cancer consists of a combination of cytoreductive surgery and platinum and taxane-based chemotherapy. However, more than 50% of women with epithelial ovarian cancer will experience a relapse and require further chemotherapy and at some point develop resistance to platinum-based drugs. Currently, guidance on the use of most chemotherapy drugs, including taxanes, is unclear for women whose epithelial ovarian cancer has recurred. Paclitaxel, topotecan, pegylated liposomal doxorubicin hydrochloride, trabectedin and gemcitabine are all licensed for use in the UK at the discretion of clinicians, following discussion with the women as to potential adverse effects. Taxanes can be given in once-weekly regimens (at a lower dose) or three-weekly regimens (at a higher dose), which may have differences in the severity of side effects and effectiveness. As relapsed disease suggests incurable disease, it is all the more important to consider side effects and the impact of treatment schedules, as well as quality of life, and not only the life-prolonging effects of treatment. OBJECTIVES: To assess the efficacy and toxicity of different taxane monotherapy regimens for women with recurrent epithelial ovarian, tubal or primary peritoneal cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase, up to 22 March 2022. Other related databases and trial registries were searched as well as grey literature and no additional studies were identified. A total of 1500 records were identified. SELECTION CRITERIA: We included randomised controlled trials of taxane monotherapy for adult women diagnosed with recurrent epithelial ovarian, tubal or primary peritoneal cancer, previously treated with platinum-based chemotherapy. We included trials comparing two or more taxane monotherapy regimens. Participants could be experiencing their first recurrence of disease or any line of recurrence. DATA COLLECTION AND ANALYSIS: Two review authors screened, independently assessed studies, and extracted data from the included studies. The clinical outcomes we examined were overall survival, response rate, progression-free survival, neurotoxicity, neutropenia, alopecia, and quality of life. We performed statistical analyses using fixed-effect and random-effects models following standard Cochrane methodology. We rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: Our literature search yielded 1500 records of 1466 studies; no additional studies were identified by searching grey literature or handsearching. We uploaded the search results into Covidence. After the exclusion of 92 duplicates, we screened titles and abstracts of 1374 records. Of these, we identified 24 studies for full-text screening. We included four parallel-group randomised controlled trials (RCTs). All trials were multicentred and conducted in a hospital setting. The studies included 981 eligible participants with recurrent epithelial ovarian cancer, tubal or primary peritoneal cancer with a median age ranging between 56 to 62 years of age. All participants had a WHO (World Health Organization) performance status of between 0 to 2. The proportion of participants with serous histology ranged between 56% to 85%. Participants included women who had platinum-sensitive (71%) and platinum-resistant (29%) relapse. Some participants were taxane pre-treated (5.6%), whilst the majority were taxane-naive (94.4%). No studies were classified as having a high risk of bias for any of the domains in the Cochrane risk of bias tool. We found that there may be little or no difference in overall survival (OS) between weekly paclitaxel and three-weekly paclitaxel, but the evidence is very uncertain (risk ratio (RR) of 0.94, 95% confidence interval (CI) 0.66 to 1.33, two studies, 263 participants, very low-certainty evidence). Similarly, there may be little or no difference in response rate (RR of 1.07, 95% CI 0.78 to 1.48, two studies, 263 participants, very low-certainty evidence) and progression-free survival (PFS) (RR of 0.83, 95% CI 0.46 to 1.52, two studies, 263 participants, very low-certainty evidence) between weekly and three-weekly paclitaxel, but the evidence is very uncertain. We found differences in the chemotherapy-associated adverse events between the weekly and three-weekly paclitaxel regimens. The weekly paclitaxel regimen may result in a reduction in neutropenia (RR 0.51, 95% 0.27 to 0.95, two studies, 260 participants, low-certainty evidence) and alopecia (RR 0.58, 95% CI 0.46 to 0.73, one study, 205 participants, low-certainty evidence). There may be little or no difference in neurotoxicity, but the evidence was very low-certainty and we cannot exclude an effect (RR 0.53, 95% CI 0.19 to 1.45, two studies, 260 participants). When examining the effect of paclitaxel dosage in the three-weekly regimen, the 250 mg/m2 paclitaxel regimen probably causes more neurotoxicity compared to the 175 mg/m2 regimen (RR 0.41, 95% CI 0.21 to 0.80, one study, 330 participants, moderate-certainty evidence). Quality-of-life data were not extractable from any of the included studies. AUTHORS' CONCLUSIONS: Fewer people may experience neutropenia when given weekly rather than three-weekly paclitaxel (low-certainty evidence), although it may make little or no difference to the risk of developing neurotoxicity (very low-certainty evidence). This is based on the participants receiving lower doses of drug more often. However, our confidence in this result is low and the true effect may be substantially different from the estimate of the effect. Weekly paclitaxel probably reduces the risk of alopecia, although the rates in both arms were high (46% versus 79%) (low-certainty evidence). A change to weekly from three-weekly chemotherapy could be considered to reduce the likelihood of toxicity, as it may have little or no negative impact on response rate (very low-certainty evidence), PFS (very low-certainty evidence) or OS (very low-certainty evidence). Three-weekly paclitaxel, given at a dose of 175 mg/m2 compared to a higher dose,probably reduces the risk of neurotoxicity.We are moderately confident in this result; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. A change to 175 mg/m2 paclitaxel (from a higher dose), if a three-weekly regimen is used, probably has little or no negative impact on PFS or OS (very low-certainty evidence).


Assuntos
Neutropenia , Neoplasias Ovarianas , Adulto , Alopecia/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/efeitos adversos , Taxoides/efeitos adversos
16.
Immunohorizons ; 6(7): 543-558, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35882421

RESUMO

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome immunodeficiency is caused by autosomal dominant gain-of-function CXCR4 mutations that promote severe panleukopenia caused by bone marrow retention of mature leukocytes. Consequently, WHIM patients develop recurrent bacterial infections; however, sepsis is uncommon. To study this clinical dichotomy, we challenged WHIM model mice with LPS. The LD50 was similar in WHIM and wild-type (WT) mice, and LPS induced acute lymphopenia in WT mice that was Cxcr4 independent. In contrast, in WHIM mice, LPS did not affect circulating T cell levels, but the B cell levels anomalously increased because of selective, cell-intrinsic, and Cxcr4 WHIM allele-dependent emergence of Cxcr4high late pre-B cells, a pattern that was phenocopied by Escherichia coli infection. In both WT and WHIM mice, the CXCR4 antagonist AMD3100 rapidly increased circulating lymphocyte levels that then rapidly contracted after subsequent LPS treatment. Thus, LPS-induced lymphopenia is CXCR4 independent, and a WHIM mutation does not increase clinical LPS sensitivity. Anomalous WT Cxcr4-independent, but Cxcr4 WHIM-dependent, promobilizing effects of LPS on late pre-B cell mobilization reveal a distinct signaling pathway for the variant receptor.


Assuntos
Agamaglobulinemia , Linfopenia , Neutropenia , Verrugas , Agamaglobulinemia/genética , Animais , Endotoxinas/uso terapêutico , Lipopolissacarídeos , Camundongos , Neutropenia/genética , Doenças da Imunodeficiência Primária , Verrugas/tratamento farmacológico , Verrugas/genética
17.
Acta Biomed ; 93(3): e2022235, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35775777

RESUMO

. INTRODUCTION:  The link between iron deficiency anemia (IDA) and neutropenia/ lymphocytopenia is not well established in the literature. This study aims at assessing the prevalence and clinical characteristics of neutropenia and lymphocytopenia in IDA patients considering the impact of iron replacement on the total and differential WBCs' count. SUBJECTS AND METHODS:  The records of all female patients with IDA who attended our hematology clinic (Jan 2018 to Jan 2020) were retrospectively reviewed. Patients with systemic or chronic diseases were excluded. Age, BMI, CBC, and iron parameters were collected before and after IV iron therapy. Results: Out of 1,567 adult females with IDA, 80 patients had leukopenia (5.1%), 64 had neutropenia (4.0%), and 20 had lymphocytopenia (1.2%). After iron therapy, their mean leukocytes, neutrophils, and lymphocytes increased significantly to 4.38 ± 1.82 ×103/L, 2.3 ±1.56 ×109/L and 1.76 ± 0.48 ×103/L, respectively. About 67% of women with IDA and neutropenia had increased ANC in response to iron therapy. However, no significant correlation was found between leukocytes, ANC, or lymphocytes with TIBC or serum iron concentration. CONCLUSIONS:  Neutropenia and/or lymphocytopenia may occur in patients with IDA and are reversible with iron therapy. Iron therapy led to the correction of anemia in 100% and increased ANC in 67%. Therefore, neutropenic women with IDA should be treated, initially only with iron, and observed for their Hb and ANC responses before starting any other treatment.


Assuntos
Anemia Ferropriva , Anemia , Deficiências de Ferro , Linfopenia , Neutropenia , Adulto , Anemia Ferropriva/complicações , Anemia Ferropriva/tratamento farmacológico , Árabes , Feminino , Hemoglobinas/análise , Humanos , Ferro/uso terapêutico , Linfopenia/complicações , Linfopenia/tratamento farmacológico , Neutropenia/complicações , Estudos Retrospectivos
18.
Int J Colorectal Dis ; 37(7): 1525-1534, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35780257

RESUMO

PURPOSE: Sunitinib offers a significant survival benefit to patients with imatinib-resistant gastrointestinal stromal tumors (GIST). However, the incidence and risk of sunitinib-induced hematologic toxicities in such a population are often overlooked and have not been well characterized. This meta-analysis was performed to assess the summary incidence and risk of hematologic toxicities secondary to sunitinib in patients with GIST. METHODS: Searches were performed in PubMed, Embase, Cochrane Library, and Web of Science as well as ClinicalTrials.gov to identify relevant studies up to April 2022. Studies with adequate safety profile, including anemia, neutropenia, and thrombocytopenia, were included to calculate the pooled incidence, relative risk (RR), and corresponding 95% confidence intervals (CIs). This study was registered with PROSPERO under number CRD42022328202. RESULTS: A total of 2593 patients from 13 studies were included in the present meta-analysis. For patients with GIST assigned to sunitinib, the overall incidences of all-grade anemia, neutropenia, and thrombocytopenia were 26.2% (95% CI, 14.9-39.4%), 41.8% (95% CI, 29.0-55.1%), and 36.4% (95% CI, 22.8-51.1%), respectively. Regarding high-grade (grades 3 and 4) events, there were 4.7% (95% CI, 3.8-5.6%) for anemia, 9.3% (95% CI, 5.6-13.7%) for neutropenia and 5.0% (95% CI, 2.9-7.3%) for thrombocytopenia. Compared to placebo arms, sunitinib was related to an increased risk of high-grade neutropenia with an RR of 10.39 (95% CI, 1.53-70.72; p = 0.017). CONCLUSIONS: Sunitinib carries a relatively high incidence of hematologic toxicities and a substantial increased risk of high-grade neutropenia in patients with GIST. Appropriate prevention and management seem to be inevitable.


Assuntos
Anemia , Antineoplásicos , Tumores do Estroma Gastrointestinal , Neutropenia , Trombocitopenia , Anemia/induzido quimicamente , Anemia/epidemiologia , Antineoplásicos/efeitos adversos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Neutropenia/epidemiologia , Pirróis/efeitos adversos , Sunitinibe/efeitos adversos , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico , Trombocitopenia/epidemiologia
19.
Anticancer Res ; 42(7): 3693-3700, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35790277

RESUMO

BACKGROUND/AIM: Eribulin is an effective chemotherapeutic agent for the treatment of metastatic breast cancer and advanced or metastatic soft-tissue sarcomas. However, severe adverse effects (SAEs) occur in 30-40% of the patients, and significantly reduce the patients' quality of life and disturb the recommended treatment schedules. Neutropenia is the main cause of treatment suspension, delay, and/or dose reductions, also leading to relative dose intensity reduction. This study aimed to examine the risk factors for SAE occurrence after eribulin treatment. PATIENTS AND METHODS: Eighty patients with metastatic breast cancer or advanced or metastatic soft tissue sarcoma who received eribulin were retrospectively evaluated. Risk factors for SAE occurrence in the first cycle were primarily assessed. In addition, factors associated with SAE occurrence during all treatment cycles were evaluated. RESULTS: SAEs in the first cycle occurred in 45% of patients. The primary SAE was neutropenia (91.7%). The incidence of SAEs during all treatment cycles was 61.3%. Multivariate analyses suggested that lower baseline neutrophil and hemoglobin levels were risk factors for SAE occurrence and severe neutropenia incidence in the first cycle. An independent factor associated with SAE occurrence during all cycles was age ≥65 years and a tendency was confirmed for baseline anemia. CONCLUSION: Baseline neutropenia and anemia were risk factors for SAE occurrence during the first eribulin treatment cycle. Age ≥65 years was also associated with SAE occurrence during all treatment cycles. Patients with these risk factors should be carefully monitored for assessment and prophylaxis.


Assuntos
Neoplasias da Mama , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neutropenia , Sarcoma , Idoso , Neoplasias da Mama/patologia , Análise Fatorial , Feminino , Furanos , Humanos , Cetonas , Neutropenia/induzido quimicamente , Qualidade de Vida , Estudos Retrospectivos , Fatores de Risco
20.
Lancet ; 400(10349): 369-379, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35908570

RESUMO

BACKGROUND: Upadacitinib, a Janus kinase inhibitor, has been shown to be effective in patients with ankylosing spondylitis. We aimed to assess the efficacy and safety of upadacitinib in non-radiographic axial spondyloarthritis. METHODS: The SELECT-AXIS 2 non-radiographic axial spondyloarthritis study was a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 113 sites across 23 countries (Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, France, Germany, Hungary, Israel, Japan, Mexico, Poland, Russia, Slovakia, South Korea, Spain, Taiwan, Turkey, Ukraine, and the USA). Eligible adults had active non-radiographic axial spondyloarthritis, with objective signs of inflammation based on MRI or elevated C-reactive protein and an inadequate response to non-steroidal anti-inflammatory drugs. Patients were randomly assigned (1:1) to receive oral upadacitinib 15 mg once daily or placebo using interactive response technology. Random treatment assignment was stratified by MRI inflammation in the sacroiliac joints and screening high-sensitivity C-reactive protein status (MRI-positive and C-reactive protein-positive, MRI-positive and C-reactive protein-negative, and MRI-negative and C-reactive protein-positive) and previous exposure to biologic disease-modifying antirheumatic drugs (yes vs no). Treatment assignment was masked from patients, investigators, study site personnel, and the study sponsor. The primary endpoint was the proportion of patients with an Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 14. Analyses were performed on the full analysis set of patients, who underwent random allocation and received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04169373. FINDINGS: Between Nov 26, 2019, and May 20, 2021, 314 patients with active non-radiographic axial spondyloarthritis were enrolled into the study, and 313 received study drug (156 in the upadacitinib group and 157 in the placebo group); 295 (94%) patients (145 in the upadacitinib group and 150 in the placebo group) received treatment for the full 14 weeks. A significantly higher ASAS40 response rate was achieved with upadacitinib compared with placebo at week 14 (70 [45%] of 156 patients vs 35 [23%] of 157 patients; p<0·0001; treatment difference 22%, 95% CI 12-32). The rate of adverse events up to week 14 was similar in the upadacitinib group (75 [48%] of 156 patients) and placebo group (72 [46%] of 157 patients). Serious adverse events and adverse events leading to discontinuation of study drug occurred in four (3%) of 156 patients in the upadacitinib group and two (1%) of 157 patients in the placebo group. Few patients had serious infections or herpes zoster in either treatment group (each event occurred in two [1%] of 156 patients in the upadacitinib group and one [1%] of 157 patients in the placebo group). Five (3%) of 156 patients in the upadacitinib group had neutropenia; no events of neutropenia occurred in the placebo group. No opportunistic infections, malignancies, major adverse cardiovascular events, venous thromboembolic events, or deaths were reported with upadacitinib treatment. INTERPRETATION: Upadacitinib significantly improved the signs and symptoms of non-radiographic axial spondyloarthritis compared with placebo at week 14. These findings support the potential of upadacitinib as a new therapeutic option in patients with active non-radiographic axial spondyloarthritis. FUNDING: AbbVie.


Assuntos
Espondiloartrite Axial , Neutropenia , Espondiloartrite Axial não Radiográfica , Adulto , Proteína C-Reativa , Método Duplo-Cego , Compostos Heterocíclicos com 3 Anéis , Humanos , Inflamação , Resultado do Tratamento
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