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1.
Gan To Kagaku Ryoho ; 47(9): 1345-1349, 2020 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-33130697

RESUMO

The study subjects consisted of 54 patients with inoperable or recurrent breast cancer who were administered a combination of palbociclib plus endocrine therapy. We examined the onset of neutropenia during the first course of treatment and evaluated the influence that various risk factors had on treatment continuity. Patients with neutropenia Grade≥3 had significantly lower relative dose intensity(RDI) values during the first course of treatment than did patients with neutropenia Grade ≤2. Patients with neutropenia Grade≥3 showed significantly longer treatment to failure than did patients with neutropenia Grade≤2. These results suggest that the degree of neutropenia during the first course of treatment might contribute to treatment continuity and that it is important to improve the curative effect by maintaining appropriate RDI and by continuously administering palbociclib in patients with neutropenia Grade≥3.


Assuntos
Neoplasias da Mama , Neutropenia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Duração da Terapia , Humanos , Recidiva Local de Neoplasia , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , Piperazinas , Piridinas , Receptor ErbB-2
2.
Exp Hematol ; 92: 51-61, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33002567

RESUMO

Eflapegrastim (Rolontis) is a long-acting granulocyte colony-stimulating factor (G-CSF) with an IgG4 Fc fragment and short polyethylene glycol linker. Current G-CSF products are administered 24 hours after chemotherapy. The present study compares the duration of neutropenia (DN) with eflapegrastim or pegfilgrastim at 0, 2, 5, or 24 hours post chemotherapy. Eflapegrastim was evaluated by G-CSF receptor binding and bone marrow cell proliferation assays in vitro. Eflapegrastim-Fc component binding to Fcγ receptors C1q and FcRn was assessed by enzyme-linked immunosorbent assay. Neutropenia was induced in rats via intraperitoneal cyclophosphamide or docetaxel/cyclophosphamide. Rats received chemotherapy followed by vehicle, pegfilgrastim, or eflapegrastim at 2, 5, or 24 hours. The difference in DN after treatment was assessed. In vitro binding to G-CSF receptor of both agents was similar. Binding to FcRn and no binding to Fcγ receptors or C1q were observed with eflapegrastim. Studies in chemotherapy-induced neutropenic rats revealed shorter DN with eflapegrastim versus pegfilgrastim. Increased levels of G-CSF in serum and marrow were observed in groups treated with eflapegrastim versus those treated with pegfilgrastim. Although eflapegrastim and pegfilgrastim have similar in vitro binding affinity, the Fc fragment in eflapegrastim increases the uptake into bone marrow, resulting in increased therapeutic potential for chemotherapy-induced neutropenia. Eflapegrastim's greater marrow resident time provided a pharmacodynamic advantage over pegfilgrastim, translating into shortened duration of neutropenia. Our findings support eflapegrastim same-day administration with chemotherapy, warranting further evaluation in patients undergoing myelosuppressive chemotherapy.


Assuntos
Filgrastim , Neutropenia/sangue , Neutropenia/tratamento farmacológico , Polietilenoglicóis , Animais , Ciclofosfamida/efeitos adversos , Ciclofosfamida/farmacologia , Docetaxel/efeitos adversos , Docetaxel/farmacologia , Filgrastim/farmacocinética , Filgrastim/farmacologia , Antígenos de Histocompatibilidade Classe I/sangue , Humanos , Masculino , Camundongos , Neutropenia/induzido quimicamente , Neutropenia/patologia , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Fc/sangue , Células U937
3.
PLoS One ; 15(10): e0236460, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112882

RESUMO

The intestinal bacterial flora of febrile neutropenic patients has been found to be significantly diverse. However, there are few reports of alterations of in adult acute myeloid leukemia (AML) patients. Stool samples of each treatment-naïve AML patient were collected the day before initiation of induction chemotherapy (pretreatment), on the first date of neutropenic fever and first date of bone marrow recovery. Bacterial DNA was extracted from stool samples and bacterial 16s ribosomal RNA genes were sequenced by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. No antimicrobial prophylaxis was in placed in all participants. Ten cases of AML patients (4 male and 6 female) were included with a median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes dominated during the period of neutropenic fever, subsequently declining after bone marrow recovery a pattern in contrast to that shown by Bacteroidetes and Proteobacteria. Enterococcus was more abundant in the febrile neutropenia period compared to pretreatment (mean difference +20.2; p < 0.0001) while Escherichia notably declined during the same period (mean difference -11.2; p = 0.0064). At the operational taxonomic unit (OTU) level, there was a significantly higher level of overall richness in the pretreatment period than in the febrile neutropenic episode (mean OTU of 203.1 vs. 131.7; p = 0.012). Both of the diversity indexes of Shannon and Simpson showed a significant decrease during the febrile neutropenic period. Adult AML patients with a first episode of febrile neutropenia after initial intensive chemotherapy demonstrated a significant decrease in gut microbiota diversity and the level of diversity remained constant despite recovery of bone marrow.


Assuntos
Bactérias/classificação , Biodiversidade , Febre/microbiologia , Microbioma Gastrointestinal , Quimioterapia de Indução/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Neutropenia/microbiologia , Adolescente , Adulto , Idoso , Bactérias/isolamento & purificação , Feminino , Febre/induzido quimicamente , Humanos , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Adulto Jovem
4.
Int J Clin Oncol ; 25(12): 2035-2043, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32926227

RESUMO

BACKGROUND: For unresectable or recurrent advanced gastric adenocarcinoma (AGC), tri-weekly administration of nanoparticle albumin-bound paclitaxel (nab-PTX) at 260 mg/m2 achieved a response rate of 27.8% in a phase II trial in Japan. However, frequent neutropenia and peripheral neuropathy limit its use in clinical settings. We, thus, conducted a single-arm phase II trial to investigate the efficacy and safety of a reduced dose (220 mg/m2) of tri-weekly nab-PTX. METHODS: Eligible patients included those with AGC and ECOG performance status of 0-2 who had received one or more prior chemotherapy containing fluoropyrimidine regimens. A reduced dose of nab-PTX (220 mg/m2) was administered tri-weekly. The primary endpoint was response rate (RR). Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease-control rate (DCR), incidence of adverse events, relative dose intensity (RDI) and proportion of patients receiving subsequent chemotherapy. RESULTS: Among 33 patients enrolled, 32 were treated with protocol therapy. RR was 3.1% [95% confidence interval (CI), 0-16.2%], which did not reach the protocol-specified threshold (p = 0.966). DCR was 37.5% (95% CI, 21.1-56.3%). Median OS and PFS were 6.3 (95% CI, 4.4-14.2) and 2.2 (95% CI, 1.8-3.1) months, respectively. RDI was 97.8%. Twenty (62.5%) patients received subsequent chemotherapy. Toxicity was relatively mild with the most common grade ≥ 3 adverse events being neutropenia (38%), anemia (13%), fatigue (19%), anorexia (16%), and peripheral neuropathy (13%). CONCLUSION: Tri-weekly nab-PTX with a reduced dose (220 mg/m2) is not recommended for AGC in a second-line or later setting, despite demonstrating less toxicity than at 260 mg/m2. Clinical trial registration The OGSG1302 trial was registered with UMIN-CTR as UMIN000000714.


Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Antineoplásicos Fitogênicos/administração & dosagem , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Albuminas/uso terapêutico , Anorexia/induzido quimicamente , Anorexia/epidemiologia , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Relação Dose-Resposta a Droga , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Paclitaxel/uso terapêutico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento
5.
Ann Hematol ; 99(11): 2477-2482, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32815018

RESUMO

Wider use of clozapine, one of the most effective antipshychotic drugs, is precluded by its propensity to cause agranulocytosis. Currently, clozapine is used for treatment-resistant schizophrenia, with mandatory blood count monitoring for the duration of treatment. Agranulocytosis occurs in up to 0.8% of patients and presents a significant medical challenge, despite decreasing mortality rates. In this paper, we review the epidemiology of clozapine-induced agranulocytosis (CLIA), advances in identifying genetic risk factors, and the preventive measures to reduce the risk of CLIA. We discuss the pathogenesis of CLIA, which, despite receiving considerable scientific attention, has not been fully elucidated. Finally, we address the clinical management and suggest the approach to clozapine re-challenge in patients with a previous episode of neutropenia. With a significant proportion of clozapine recipients in Western hemisphere being Black, we comment on the importance of recognizing benign ethnic neutropenia as a potential impediment to clozapine administration. This review aims to aid haematologists and psychiatrists to jointly manage neutropenia and agranulocytosis caused by clozapine.


Assuntos
Grupo com Ancestrais do Continente Africano , Clozapina/efeitos adversos , Neutropenia , Clozapina/uso terapêutico , Humanos , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Neutropenia/etnologia , Neutropenia/prevenção & controle , Fatores de Risco
6.
Ann Hematol ; 99(10): 2385-2392, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32748163

RESUMO

Up to 30% of patients with classical Hodgkin lymphoma (cHL) are not responsive to frontline therapy or relapse after primary treatment. In these cases, autologous hematopoietic stem cell transplantation (AHSCT) is the standard of care. The combination of brentuximab vedotin and bendamustine (BV + B) is an effective salvage regimen in this challenging subpopulation. This nationwide multicenter study investigated the real-world efficacy and safety of the BV + B regimen as a bridge to AHSCT in patients with primary refractory or relapsed cHL. A total of 41 cHL patients underwent AHSCT after receiving at least 1 cycle of BV + B (with brentuximab vedotin given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1-2 every 4 weeks). After a median of 3 (1-6) cycles of BV + B, the objective response rate was 78%, with 29 (70.7%) patients achieving complete remission. Twelve (29.3%) patients relapsed after AHSCT, 2 (4.9%) of them died, while 2 (4.9%) patients are lost to follow-up. After a median of 17 months of follow-up, the estimated 2-year overall- and progression-free survival after AHSCT was 93 and 62%, respectively. Features of advanced disease at recurrence (p = 0.038) and the presence of stage IV cHL at relapse (p = 0.024) are strong predictor markers of unfavorable outcomes. Twenty-four (58.5%) patients experienced adverse events of any grade, while no grade IV toxicities were reported. BV + B is an effective salvage option with a manageable toxicity profile in cHL. The real-world safety and efficacy of this combination are similar to the observations made on the study population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Terapia de Salvação , Adolescente , Adulto , Idoso , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Brentuximab Vedotin/administração & dosagem , Brentuximab Vedotin/efeitos adversos , Terapia Combinada , Avaliação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/terapia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Neutropenia/induzido quimicamente , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Tomografia por Emissão de Pósitrons , Intervalo Livre de Progressão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
7.
Sci Rep ; 10(1): 13486, 2020 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778670

RESUMO

Genetic polymorphisms in drug metabolizing enzymes and drug transporters may affect irinotecan toxicity. Although genetic polymorphisms have been shown to influence the irinotecan toxicity, data are limited in Thai population. Thus, the aim of this study was to assess the allele and genotype frequencies and the relationship between CYP3A4/5, DPYD, UGT1A1, ABCB1, and ABCC2 genetic variations and irinotecan-induced toxicity in Thai colorectal cancer patients. One hundred and thirty-two patients were genotyped, and the effect of genetic variations on irinotecan-induced toxicity was assessed in 66 patients who received irinotecan-based chemotherapy. Allele frequencies of ABCB1 c.1236C > T, ABCB1 c.3435C > T, ABCC2 c.3972C > T, ABCG2 c.421C > A, CYP3A4*1B, CYP3A4*18, CYP3A5*3, DPYD*5, UGT1A1*28, and UGT1A1*6 were 0.67, 0.43, 0.23, 0.27, 0.01, 0.02, 0.64, 0.19, 0.16, and 0.09, respectively. DPYD*2A and DPYD c.1774C > T variants were not detected in our study population. The ABCC2 c.3972C > T was significantly associated with grade 1-4 neutropenia (P < 0.012) at the first cycle. Patients carrying both UGT1A1*28 and *6 were significantly associated with severe neutropenia at the first (P < 0.001) and second (P = 0.017) cycles. In addition, patients carrying UG1A1*28 and *6 had significantly lower absolute neutrophil count (ANC) nadir at first (P < 0.001) and second (P = 0.001) cycles. This finding suggests that UGT1A1*28, *6, and ABCC2 c.3972C > T might be an important predictor for irinotecan-induced severe neutropenia.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Irinotecano/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Alelos , Citocromo P-450 CYP3A/genética , Feminino , Frequência do Gene/genética , Variação Genética/genética , Genótipo , Glucuronosiltransferase/genética , Humanos , Irinotecano/metabolismo , Irinotecano/uso terapêutico , Masculino , Proteínas de Membrana Transportadoras/genética , Pessoa de Meia-Idade , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Neutropenia/induzido quimicamente , Polimorfismo Genético/genética , Tailândia/epidemiologia
8.
BMC Infect Dis ; 20(1): 535, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703183

RESUMO

BACKGROUND: Breakthrough invasive fungal infections (bIFIs) are an area of concern in the scarcity of new antifungals. The mixed form of bIFIs is a rare phenomenon but could be potentially a troublesome challenge when caused by azole-resistant strains or non-Aspergillus fumigatus. To raise awareness and emphasize diagnostic challenges, we present a case of mixed bIFIs in a child with acute lymphoblastic leukemia. CASE PRESENTATION: A newly diagnosed 18-month-old boy with acute lymphoblastic leukemia was complicated with prolonged severe neutropenia after induction chemotherapy. He experienced repeated episodes of fever due to extended-spectrum beta-lactamase-producing Escherichia coli bloodstream infection and pulmonary invasive fungal infection with Aspergillus fumigatus (early-type bIFIs) while receiving antifungal prophylaxis. Shortly after pulmonary involvement, his condition aggravated by abnormal focal movement, loss of consciousness and seizure. Cerebral aspergillosis with Aspergillus niger diagnosed after brain tissue biopsy. The patient finally died despite 108-day antifungal therapy. CONCLUSIONS: Mixed bIFIs is a rare condition with high morbidity and mortality in the patients receiving immunosuppressants for hematological malignancies. This case highlights the clinical importance of Aspergillus identification at the species level in invasive fungal infections with multiple site involvement in the patients on antifungal prophylaxis.


Assuntos
Antifúngicos/uso terapêutico , Aspergillus fumigatus/imunologia , Aspergillus niger/genética , Coinfecção/diagnóstico , Aspergilose Pulmonar Invasiva/diagnóstico , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Neuroaspergilose/diagnóstico , Antígenos de Fungos/análise , Aspergillus fumigatus/isolamento & purificação , Aspergillus niger/isolamento & purificação , Cerebelo/microbiologia , Cerebelo/patologia , Criança , Coinfecção/microbiologia , Evolução Fatal , Humanos , Quimioterapia de Indução/efeitos adversos , Lactente , Aspergilose Pulmonar Invasiva/sangue , Aspergilose Pulmonar Invasiva/microbiologia , Masculino , Neuroaspergilose/microbiologia , Neutropenia/induzido quimicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
9.
Support Care Cancer ; 28(11): 5085-5097, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32621264

RESUMO

BACKGROUND: PEGylated granulocyte colony-stimulating factor (G-CSF) is a safe alternative to G-CSF to improve chemotherapy-induced neutropenia (CIN). This superiority has resulted in its increased use by physicians; however, the superiority of PEGylated G-CSF for CIN in breast cancer has not been conclusively determined. OBJECTIVES: To assess the superiority of PEGylated G-CSF for CIN in breast cancer in terms of effectiveness and safety via a systematic review and meta-analysis. METHODS: A literature search in PubMed, Embase, Cochrane Library, and Web of Science was performed for eligible studies published from database inception to December 2019. All studies comparing PEGylated G-CSF and G-CSF for CIN of breast cancer were reviewed. After literature selection, data extraction and quality assessment were performed by two reviewers independently. Meta-analysis was conducted using Revman, version 5.2. RESULTS: Nine randomized controlled trials were finally identified. The publication bias of these studies was acceptable. For the endpoint of effectiveness, analysis of the incidence/duration of grade ≥ 3 neutropenia, the duration of grade 4 neutropenia, the incidence of febrile neutropenia (FN), and the time to absolute neutrophil count recovery showed no advantage of PEGylated G-CSF over G-CSF for CIN of breast cancer (P > 0.05), with the premise of a sufficient dose of G-CSF according to the guidelines. No significant differences in grade 4 adverse events were observed between the groups (P = 0.29), and PEGylated G-CSF did not increase the incidence of skeletal and/or muscle pain compared with G-CSF (P = 0.32). CONCLUSION: PEGylated G-CSF was as effective and safe as G-CSF to reduce CIN in breast cancer but did not show an obvious superiority. However, in clinical practice, PEGylated G-CSF has an obvious advantage in terms of convenience, which could improve patient's quality of life.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neutropenia/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neutropenia Febril Induzida por Quimioterapia/tratamento farmacológico , Feminino , Humanos , Neutropenia/induzido quimicamente , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/administração & dosagem
10.
Int J Clin Oncol ; 25(12): 2151-2157, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32715356

RESUMO

BACKGROUND: Significant advancements have been achieved in the quality of treatment for relapsed/refractory multiple myeloma (RRMM). Currently, daratumumab (DARA) is a highly effective drug widely used for RRMM; however, the knowledge on its efficacy and safety in Japanese patients remains limited. Accordingly, we aimed to evaluate the efficacy and safety of DARA therapy for RRMM. METHODS: We reviewed the medical records of patients who received DARA combination therapy and evaluated its efficacy and safety in our hospital. RESULTS: DARA was administered to 44 patients between October 2017 and March 2019. The median number of previous therapies was three (range 1-9). The rates of ≥ complete response and overall response were 27.3% and 61.4%, respectively. The median progression-free survival (PFS) duration was 12.3 months [95% confidence interval (CI) 5.1 to not reached (NR)] and estimated 2-year overall survival rate was 63.7% (95% CI 46.9-76.5%). In the multivariate analysis, patients with ≥ three previous lines of therapy and mass lesions showed significantly shorter PFS durations. The observed grade 3/4 adverse events (≥ 10%) included neutropenia (59.0%), thrombocytopenia (29.5%), anemia (36.4%), lymphopenia (38.6%) and febrile neutropenia (18.2%). None of the patients discontinued DARA therapy in spite of these AEs. CONCLUSION: DARA is an effective treatment option for most patients and is tolerable. However, patients with heavy treatment before DARA therapy and mass lesions are likely to show poorer outcomes. Our findings suggest the use of DARA therapy early in the course of the disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Neutropenia/induzido quimicamente , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
J Oral Maxillofac Surg ; 78(12): 2219-2225, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32628932

RESUMO

An association between granulocyte colony-stimulating factor therapy (G-CSFT) in patients with glycogen storage disease type Ib (GSDIb) and the development of giant cell lesions of the maxillofacial complex has emerged. We have reported, to the best of our knowledge, the fourth case of giant cell granuloma (GCG) in a patient with GSDIb undergoing G-CSFT. GSDIb can present with hypoglycemia, hypertriglyceridemia, and neutropenia. G-CSFT has often been used in the treatment of recurrent infections or sepsis caused by neutropenia and to treat inflammatory bowel disease and diarrhea. The current reported data are lacking in both the association and the potential causation of G-CSFT and the development of giant cell tumors. Given the prevalence of GSDIb and its therapy, oral and maxillofacial surgeons should be aware of the tumorigenic potential of G-CSFT in patients with GSDIb. In the present report, we have described the case of a 17-year-old patient with GSDIb undergoing GCSFT who presented with a peripheral and central GCG. She was treated but presented again 13 months later with concerns for a new primary lesion. We have also discussed GSDIb, G-CSFT, and the current data, highlighting the association between G-CSFT for GSDIb, the potential mechanism of GCG development, the use of adjuvant therapy, and the need for close follow-up of this population. The purpose of the present case report is to highlight the presentation, management, and follow-up of giant cell lesions in patients with GSDIb treated with G-CSFT.


Assuntos
Doença de Depósito de Glicogênio Tipo I , Neutropenia , Sepse , Adolescente , Feminino , Fator Estimulador de Colônias de Granulócitos , Humanos , Neutropenia/induzido quimicamente , Neutrófilos
12.
Clin Drug Investig ; 40(10): 915-926, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32691244

RESUMO

Idiosyncratic drug-induced neutropenia (DIN) is a rare, potentially fatal adverse reaction. A literature search was performed on Pubmed and Embase, targeting articles indicating neutropenia as a complication during the treatment of non-neoplastic dermatological disorders. In 66 identified articles, the common incriminated drugs included conventional oral immunomodulators, topical cytotoxic agents, antibacterials, antifungals, biologics and targeted synthetic disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs, and retinoids, with dapsone being reported most often. The duration of drug exposure before the diagnosis of neutropenia varied, but mostly ranged from days to weeks. The majority of patients recovered after drug discontinuation and supportive management including antibiotics and granulocyte colony-stimulating factor, but fatal cases were reported. The proposed pathogenesis of DIN consists of direct drug toxicity and immune-mediated reaction. Certain genetic variants, individual variability in enzyme efficiency, and concomitant use of other drugs may increase the risk of DIN. Being familiar with the most commonly implicated agents and risk factors helps early identification and prompt management of this potentially fatal complication.


Assuntos
Antineoplásicos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Neutropenia/induzido quimicamente , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos
13.
Tumori ; 106(4): 273-280, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32538316

RESUMO

Neutropenia is the most frequent side effect of commercially available myelosuppressive drugs and its most significant complication is febrile neutropenia. It is associated with increased hospital admissions and higher probability of death. Prophylaxis with the administration of granulocyte colony-stimulating factor can prevent neutropenia caused by anticancer drugs. The correct administration of these drugs and the management of febrile neutropenia are extremely important in the treatment of patients with cancer.


Assuntos
Antineoplásicos/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias/tratamento farmacológico , Neutropenia/tratamento farmacológico , Antineoplásicos/uso terapêutico , Gerenciamento Clínico , Guias como Assunto , Humanos , Quimioterapia de Indução/efeitos adversos , Neoplasias/complicações , Neoplasias/patologia , Neutropenia/induzido quimicamente , Neutropenia/patologia
15.
N Engl J Med ; 382(23): 2207-2219, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32492302

RESUMO

BACKGROUND: Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin's lymphoma are limited. METHODS: We conducted an open-label, international, randomized, phase 3 trial involving patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin's lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. The primary end point was event-free survival. Overall survival and toxic effects were also assessed. RESULTS: Analyses were based on 328 patients who underwent randomization (164 patients per group); 85.7% of the patients had Burkitt's lymphoma. The median follow-up was 39.9 months. Events were observed in 10 patients in the rituximab-chemotherapy group and in 28 in the chemotherapy group. Event-free survival at 3 years was 93.9% (95% confidence interval [CI], 89.1 to 96.7) in the rituximab-chemotherapy group and 82.3% (95% CI, 75.7 to 87.5) in the chemotherapy group (hazard ratio for primary refractory disease or first occurrence of progression, relapse after response, death from any cause, or second cancer, 0.32; 95% CI, 0.15 to 0.66; one-sided P = 0.00096, which reached the significance level required for this analysis). Eight patients in the rituximab-chemotherapy group died (4 deaths were disease-related, 3 were treatment-related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths were disease-related, and 3 were treatment-related) (hazard ratio, 0.36; 95% CI, 0.16 to 0.82). The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab-chemotherapy group and 24.2% in the chemotherapy group (P = 0.07); events were related mainly to febrile neutropenia and infection. Approximately twice as many patients in the rituximab-chemotherapy group as in the chemotherapy group had a low IgG level 1 year after trial inclusion. CONCLUSIONS: Rituximab added to standard LMB chemotherapy markedly prolonged event-free survival and overall survival among children and adolescents with high-grade, high-risk, mature B-cell non-Hodgkin's lymphoma and was associated with a higher incidence of hypogammaglobulinemia and, potentially, more episodes of infection. (Funded by the Clinical Research Hospital Program of the French Ministry of Health and others; ClinicalTrials.gov number, NCT01516580.).


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Rituximab/administração & dosagem , Adolescente , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Infecções/etiologia , Infusões Intravenosas , Estimativa de Kaplan-Meier , Linfoma de Células B/mortalidade , Masculino , Neutropenia/induzido quimicamente , Intervalo Livre de Progressão , Rituximab/efeitos adversos
16.
BMC Psychiatry ; 20(1): 279, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503471

RESUMO

Clozapine remains the only drug treatment likely to benefit patients with treatment resistant schizophrenia. Its use is complicated by an increased risk of neutropenia and so there are stringent monitoring requirements and restrictions in those with previous neutropenia from any cause or from clozapine in particular. Despite these difficulties clozapine may yet be used following neutropenia, albeit with caution. Having had involvement with 14 cases of clozapine use in these circumstances we set out our approach to the assessment of risks and benefits, risk mitigation and monitoring with a practical guide.


Assuntos
Antipsicóticos/farmacologia , Clozapina/efeitos adversos , Clozapina/farmacologia , Neutropenia/induzido quimicamente , Esquizofrenia/tratamento farmacológico , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Clozapina/administração & dosagem , Humanos
17.
Int J Clin Oncol ; 25(10): 1793-1799, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32567012

RESUMO

BACKGROUND: The aim of this study was to explore the efficacy and safety of nab-paclitaxel as second-line chemotherapy for advanced gastric cancer with modified dose reduction criteria by which the doses were manipulated earlier. METHODS: Gastric cancer patients who developed progression during the fluoropyrimidine-containing first-line chemotherapy were assigned to receive nab-paclitaxel (260 mg/m2) by triweekly administration. Dose reduction was regulated according to predefined toxicity criteria which included neutropenia less than 1000/mm3 and/or peripheral sensory neuropathy of grade 2 or more. The primary endpoint was progression-free survival. RESULTS: A total of 50 patients were enrolled, 47 of whom were eligible for efficacy analyses. The median number of treatment cycles and relative dose intensity given per patient was four (range 1-25), and 90% (range 60-100). Of total administration throughout the trial of 280 cycles, dose reduction was required in 50 cycles. The median progression-free survival was 3.5 months (95% confidence interval 2.5-4.4) that met the primary endpoint. The median overall survival was 9.0 months (95% confidence interval 6.8-11.8), overall response rate was 16% (95% confidence interval 2-30), and disease control rate was 72% (95% confidence interval 54-90). The median time to treatment failure was 3.5 months (95% confidence interval 2.5-4.4). Adverse events of grade 3 or worse included neutropenia in 49%, and peripheral sensory neuropathy in 11%. Febrile neutropenia occurred only in one patient (2%). CONCLUSION: The modified dose reduction criteria for triweekly administration of nab-paclitaxel resulted in decreased incidence of severe peripheral sensory neuropathy without decline in efficacy.


Assuntos
Albuminas/administração & dosagem , Albuminas/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/efeitos adversos , Estudos Prospectivos , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Falha de Tratamento
18.
Br J Radiol ; 93(1113): 20190693, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32462888

RESUMO

OBJECTIVE: The aim of this study is to characterize chest CT findings of neutropenic patients with proven/probable invasive pulmonary aspergillosis (IPA). METHODS: Hematological cancer patients admitted to our institution (2007-2017) were retrospectively enrolled if the diagnostic criteria of proven/probable IPA during the neutropenia were met (EORTC/MSG). Galactomannan (GM) was routinely measured in serum and chest CT-scan was routinely performed in case of recurrent/persistent fever. Bronchoscopy was performed in case of chest CT-scan abnormalities. Chest CT-scan and GM dosage were analyzed at the time of IPA suspicion. Chest lesions were classified using a clinical report form by two expert radiologists. RESULTS: 35 patients were identified. Peribronchial focal lesions were observed in 29 IPA (82.9%) by the first radiologist and in 31 (88.5%) by the second (k = 0.768). 12 weeks mortality was 20%. CONCLUSION: Peribronchial focal lesions are a common finding in early-IPA whatever the GM value during neutropenia and our findings reinforce the efficiency of a preemptive approach. ADVANCES IN KNOWLEDGE;: Peribronchial focal lesions, which are classically described in airway invasive aspergillosis, are a common finding in early-IPA in hematological cancer patients with prolonged neutropenia regardless of the GM value, and such peribronchial lesions should reinforce the possibility of IPA.


Assuntos
Broncopatias/diagnóstico por imagem , Neoplasias Hematológicas/complicações , Aspergilose Pulmonar Invasiva/diagnóstico por imagem , Neutropenia/complicações , Tomografia Computadorizada por Raios X , Adulto , Idoso , Biomarcadores/sangue , Broncoscopia , Feminino , Neoplasias Hematológicas/sangue , Humanos , Aspergilose Pulmonar Invasiva/sangue , Masculino , Mananas/sangue , Pessoa de Meia-Idade , Neutropenia/sangue , Neutropenia/induzido quimicamente , Prevalência , Estudos Retrospectivos , Adulto Jovem
19.
Lancet Haematol ; 7(6): e456-e468, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32359506

RESUMO

BACKGROUND: The emergence of highly active novel agents has led some to question the role of autologous haematopoietic stem-cell transplantation (HSCT) and subsequent consolidation therapy in newly diagnosed multiple myeloma. We therefore compared autologous HSCT with bortezomib-melphalan-prednisone (VMP) as intensification therapy, and bortezomib-lenalidomide-dexamethasone (VRD) consolidation therapy with no consolidation. METHODS: In this randomised, open-label, phase 3 study we recruited previously untreated patients with multiple myeloma at 172 academic and community practice centres of the European Myeloma Network. Eligible patients were aged 18-65 years, had symptomatic multiple myeloma stage 1-3 according to the International Staging System (ISS), measurable disease (serum M protein >10 g/L or urine M protein >200 mg in 24 h or abnormal free light chain [FLC] ratio with involved FLC >100 mg/L, or proven plasmacytoma by biopsy), and WHO performance status grade 0-2 (grade 3 was allowed if secondary to myeloma). Patients were first randomly assigned (1:1) to receive either four 42-day cycles of bortezomib (1·3 mg/m2 administered intravenously or subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) combined with melphalan (9 mg/m2 administered orally on days 1-4) and prednisone (60 mg/m2 administered orally on days 1-4) or autologous HSCT after high-dose melphalan (200 mg/m2), stratified by site and ISS disease stage. In centres with a double HSCT policy, the first randomisation (1:1:1) was to VMP or single or double HSCT. Afterwards, a second randomisation assigned patients to receive two 28-day cycles of consolidation therapy with bortezomib (1·3 mg/m2 either intravenously or subcutaneously on days 1, 4, 8, and 11), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12) or no consolidation; both groups received lenalidomide maintenance therapy (10 mg orally on days 1-21 of a 28-day cycle). The primary outcomes were progression-free survival from the first and second randomisations, analysed in the intention-to-treat population, which included all patients who underwent each randomisation. All patients who received at least one dose of study drugs were included in the safety analyses. This study is registered with the EU Clinical Trials Register (EudraCT 2009-017903-28) and ClinicalTrials.gov (NCT01208766), and has completed recruitment. FINDINGS: Between Feb 25, 2011, and April 3, 2014, 1503 patients were enrolled. 1197 patients were eligible for the first randomisation, of whom 702 were assigned to autologous HSCT and 495 to VMP; 877 patients who were eligible for the first randomisation underwent the second randomisation to VRD consolidation (n=449) or no consolidation (n=428). The data cutoff date for the current analysis was Nov 26, 2018. At a median follow-up of 60·3 months (IQR 52·2-67·6), median progression-free survival was significantly improved with autologous HSCT compared with VMP (56·7 months [95% CI 49·3-64·5] vs 41·9 months [37·5-46·9]; hazard ratio [HR] 0·73, 0·62-0·85; p=0·0001). For the second randomisation, the number of events of progression or death at data cutoff was lower than that preplanned for the final analysis; therefore, the results from the second protocol-specified interim analysis, when 66% of events were reached, are reported (data cutoff Jan 18, 2018). At a median follow-up of 42·1 months (IQR 32·3-49·2), consolidation therapy with VRD significantly improved median progression-free survival compared with no consolidation (58·9 months [54·0-not estimable] vs 45·5 months [39·5-58·4]; HR 0·77, 0·63-0·95; p=0·014). The most common grade ≥3 adverse events in the autologous HSCT group compared to the VMP group included neutropenia (513 [79%] of 652 patients vs 137 [29%] of 472 patients), thrombocytopenia (541 [83%] vs 74 [16%]), gastrointestinal disorders (80 [12%] vs 25 [5%]), and infections (192 [30%] vs 18 [4%]). 239 (34%) of 702 patients in the autologous HSCT group and 135 (27%) of 495 in the VMP group had at least one serious adverse event. Infection was the most common serious adverse event in each of the treatment groups (206 [56%] of 368 and 70 [37%] of 189). 38 (12%) of 311 deaths from first randomisation were likely to be treatment related: 26 (68%) in the autologous HSCT group and 12 (32%) in the VMP group, most frequently due to infections (eight [21%]), cardiac events (six [16%]), and second primary malignancies (20 [53%]). INTERPRETATION: This study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. FUNDING: Janssen and Celgene.


Assuntos
Quimioterapia de Consolidação/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Mieloma Múltiplo/tratamento farmacológico , Transplante Autólogo/métodos , Administração Intravenosa , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/administração & dosagem , Bortezomib/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Intervalo Livre de Doença , Feminino , Gastroenteropatias/induzido quimicamente , Gastroenteropatias/epidemiologia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Infecções/induzido quimicamente , Infecções/epidemiologia , Injeções Subcutâneas , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Masculino , Melfalan/administração & dosagem , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Proteínas do Mieloma/análise , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Plasmocitoma/patologia , Prednisona/administração & dosagem , Prednisona/uso terapêutico , Trombocitopenia/induzido quimicamente , Trombocitopenia/epidemiologia , Transplante Autólogo/mortalidade
20.
Int J Clin Oncol ; 25(9): 1624-1634, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32472208

RESUMO

PURPOSE: To evaluate the efficacy and toxicity of metronomic oral vinorelbine monotherapy in patients with stage IIIB/IV and advanced non-small cell lung cancer (NSCLC). METHODS: The PubMed, Embase, Cochrane library, Wanfang, and CNKI databases were searched for relevant studies. The overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of severe adverse events (grade ≥ 3 adverse events; grade 3/4 AEs) were calculated using the methods of merging ratios and means. Merged ratios and means and their 95% confidence intervals (CIs) were used to descriptively analyze the efficacy and toxicity of metronomic oral vinorelbine monotherapy in patients with stage IIIB/IV and advanced NSCLC. RESULTS: The ORR and DCR achieved with metronomic oral vinorelbine monotherapy were 12% (95% CI 5-20) and 48% (95% CI 38-59), respectively. Median PFS and OS were 3.46 months (95% CI 2.49-4.43) and 8.22 months (95% CI 7.21-9.24), respectively. The incidence of grade 3/4 AEs was 16% (95% CI 10-22). The more common grade 3/4 AEs were neutropenia 9% (95% CI 2-20) and leukopenia 8% (95% CI 1-19). CONCLUSION: Metronomic oral vinorelbine monotherapy has a certain effect on patients with stage IIIB/IV and advanced NSCLC, especially for untreated elderly patients. It offers the advantages of convenience, lower cost and acceptable incidence of severe adverse events.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Vinorelbina/administração & dosagem , Administração Metronômica , Antineoplásicos Fitogênicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos como Assunto , Humanos , Leucopenia/induzido quimicamente , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neutropenia/induzido quimicamente , Intervalo Livre de Progressão , Resultado do Tratamento , Vinorelbina/efeitos adversos
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