RESUMO
Importance: Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule with efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). Objective: To evaluate event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant. Design, Setting, and Participants: In this randomized phase 3 clinical trial, patients were enrolled November 2015 to July 2019 (data cutoff, July 17, 2019). Investigators at 47 centers in 13 countries enrolled children older than 28 days and younger than 18 years with high-risk first-relapse B-ALL in morphologic complete remission (M1 marrow, <5% blasts) or with M2 marrow (blasts ≥5% and <25%) at randomization. Intervention: Patients were randomized to receive 1 cycle of blinatumomab (n = 54; 15 µg/m2/d for 4 weeks, continuous intravenous infusion) or chemotherapy (n = 54) for the third consolidation. Main Outcomes and Measures: The primary end point was event-free survival (events: relapse, death, second malignancy, or failure to achieve complete remission). The key secondary efficacy end point was overall survival. Other secondary end points included minimal residual disease remission and incidence of adverse events. Results: A total of 108 patients were randomized (median age, 5.0 years [interquartile range {IQR}, 4.0-10.5]; 51.9% girls; 97.2% M1 marrow) and all patients were included in the analysis. Enrollment was terminated early for benefit of blinatumomab in accordance with a prespecified stopping rule. After a median of 22.4 months of follow-up (IQR, 8.1-34.2), the incidence of events in the blinatumomab vs consolidation chemotherapy groups was 31% vs 57% (log-rank P < .001; hazard ratio [HR], 0.33 [95% CI, 0.18-0.61]). Deaths occurred in 8 patients (14.8%) in the blinatumomab group and 16 (29.6%) in the consolidation chemotherapy group. The overall survival HR was 0.43 (95% CI, 0.18-1.01). Minimal residual disease remission was observed in more patients in the blinatumomab vs consolidation chemotherapy group (90% [44/49] vs 54% [26/48]; difference, 35.6% [95% CI, 15.6%-52.5%]). No fatal adverse events were reported. In the blinatumomab vs consolidation chemotherapy group, the incidence of serious adverse events was 24.1% vs 43.1%, respectively, and the incidence of adverse events greater than or equal to grade 3 was 57.4% vs 82.4%. Adverse events leading to treatment discontinuation were reported in 2 patients in the blinatumomab group. Conclusions and Relevance: Among children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab compared with standard intensive multidrug chemotherapy before allogeneic hematopoietic stem cell transplant resulted in an improved event-free survival at a median of 22.4 months of follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT02393859.
Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Imunoterapia , Leucemia de Células B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Anticorpos Biespecíficos/efeitos adversos , Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Terapia Combinada , Quimioterapia de Consolidação/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Leucemia de Células B/mortalidade , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Fatores de Risco , Taxa de SobrevidaRESUMO
Asparagine levels in cerebrospinal fluid and serum asparaginase activity were monitored in children with acute lymphoblastic leukemia treated with pegylated-asparaginase. The drug was given intravenously at a dose of 2,500 IU/m2 on days 12 and 26. Serum and cerebrospinal fluid samples obtained on days 33 and 45 were analyzed centrally. Since physiological levels of asparagine in the cerebrospinal fluid of children and adolescents are 4-10 µmol/L, in this study asparagine depletion was considered complete when the concentration of asparagine was ≤0.2 µmol/L, i.e. below the lower limit of quantification of the assay used. Over 24 months 736 patients (AIEOP n=245, BFM n=491) and 903 cerebrospinal fluid samples (n=686 on day 33 and n=217 on day 45) were available for analysis. Data were analyzed separately for the AIEOP and BFM cohorts and yielded superimposable results. Independently of serum asparaginase activity levels, cerebrospinal fluid asparagine levels were significantly reduced during the investigated study phase but only 28% of analyzed samples showed complete asparagine depletion while relevant levels, ≥1 µmol/L, were still detectable in around 23% of them. Complete cerebrospinal fluid asparagine depletion was found in around 5-6% and 33-37% of samples at serum asparaginase activity levels <100 and ≥ 1,500 IU/L, respectively. In this study cerebrospinal fluid asparagine levels were reduced during pegylated-asparaginase treatment, but complete depletion was only observed in a minority of patients. No clear threshold of serum pegylated-asparaginase activity level resulting in complete cerebrospinal fluid asparagine depletion was identified. The consistency of the results found in the two independent data sets strengthen the observations of this study. Details of the treatment are available in the European Clinical Trials Database at https://www.clin-icaltrialsregister.eu/ctr-search/trial/2007-004270-43/IT.
Assuntos
Asparaginase/uso terapêutico , Asparagina/líquido cefalorraquidiano , Polietilenoglicóis/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidiano , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Áustria , Criança , Pré-Escolar , República Tcheca , Monitoramento de Medicamentos , Feminino , Alemanha , Humanos , Lactente , Itália , MasculinoRESUMO
OBJECTIVES: To assess the prevalence and morphologic characterization of pulmonary nodules in children on a chest computed tomography (CT). METHODS: Two hundred and fifty-nine trauma chest CTs in children aged 0-18 years were retrospectively reviewed by two radiologists, each with more than 10 years of experience. Images were acquired on a 64-row CT. Pulmonary lobes with trauma affections such as contusion or haemorrhage were excluded. All pulmonary nodules were evaluated for distance from the pleural surface, location, calcification and size on axial slices. RESULTS: A total of 1,190/1,295 (92%) pulmonary lobes without traumatic injury were included in this study. In 86 of 259 (33%) patients, 131 pulmonary nodules were detected. Number of nodules per patient ranged from 1 to 4. Calcifications were seen in 19% (25) of all nodules. Diameters ranged from 1 to 5 mm. 59% (77) were located in the lower lobes, 9% (12) in the middle lobe and 32% (42) in the upper lobes. 84% of the non-calcified nodules >2 mm showed a slightly angular or triangular (mostly pleural nodes) shape. CONCLUSIONS: Pulmonary nodules smaller than 5 mm can be detected frequently in children without malignant disease and are predominantly located in the lower lobes. KEY POINTS: ⢠Pulmonary nodules in children with trauma CTs were retrospectively analysed ⢠Pulmonary nodules seen on CT are frequent in children without malignant disease ⢠Nodules in this group are more frequent in the lower lobes ⢠No age dependency for the number of pulmonary nodules in children was observed.
Assuntos
Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Pulmão/diagnóstico por imagem , Masculino , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: Response (tumour volume reduction) to induction chemotherapy has been used to stratify secondary local and systemic treatment of Intergroup Rhabdomyosarcoma Study Group III (IRSG-III) embryonal rhabdomyosarcoma (RME) in consecutive CWS-trials. To evaluate its actual impact we studied response-related treatment and outcomes. PROCEDURE: Patients with IRSG-III RME <21 years and non-response (NR, <33% volume reduction) in five consecutive CWS-trials were analysed and compared with partial responders (PAR, ≥ 33% reduction). The NR was reviewed and sub-classified as Objective Response (OR, <0%-33% reduction) or Stable/Progressive Disease (SPD). RESULTS: Fifty-nine of 529 patients had NR (n = 34 OR, n = 25 SPD). Primary risk-factors including age, tumour size, and TN-classification did not differ between NR and PAR groups but NR had more patients with unfavourable sites comparatively (P = 0.04). There were no differences in primary risk-factors between OR and SPD. Significant factors associated with poor outcome in multivariate analysis were NR, TN-classification, age >10 years, tumour size >5 cm and therapy in older trials. After response assessment n = 24 NR continued to receive induction chemotherapy, n = 32 received other combinations and n = 3 no further chemotherapy. Forty-two non-responders were irradiated, and the tumours were completely resected in n = 20. After a median follow-up of 8 years, 34 NR are alive. Seventeen of 21 failures leading to disease-related deaths were locoregional. The five-year overall survival rate (OS) was 76 ± 4% for PAR, 79 ± 14% for OR, but only 40 ± 19% for SPD (P < 0.001). CONCLUSION: Response to induction chemotherapy appears to be an important surrogate marker of poor outcome in patients with SPD largely due to ineffective local control.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Rabdomiossarcoma Embrionário/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Metástase Linfática , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Rabdomiossarcoma Embrionário/mortalidade , Rabdomiossarcoma Embrionário/patologia , Taxa de Sobrevida , Carga Tumoral , Adulto JovemRESUMO
The aim of this study was to analyze in detail the site of metastasis of stage 4 Wilms tumor (WT) and its correlation with outcome. The databases from 3 major European pediatric cancer institutions were screened for children with WT between 1994 and 2011. Of 208 children identified, 31 (14.9%) had metastases at diagnosis. The lung was affected in 29 children (93.5%) and the liver in 6 children (19.4%). Twenty-seven children (87.1%) had metastases isolated to 1 organ, with the lung being the most common site (80.7%). Five-year overall survival was significantly better in those children with distant disease in either lung or liver (95.8%) compared with those affected in both lung and liver (57.1%, P=0.028). Further, prognostic markers were the response of metastases to preoperative chemotherapy (P=0.0138), high-risk histology (P=0.024), and local stage (P=0.026). Five-year overall survival was 82.1% and 5-year event-free survival was 67.9%. The overall follow-up time was 74.1 and 87.2 (2 to 151) months among survivors, and the treatment-related complication rate was 16.7%. In conclusion, in our series of stage 4 WT, prognosis was excellent if histology was favorable, metastatic disease was isolated to either lungs or liver, and if metastases responded to preoperative chemotherapy.
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Tumor de Wilms/mortalidade , Tumor de Wilms/patologia , Criança , Pré-Escolar , Terapia Combinada , Bases de Dados Factuais , Feminino , Seguimentos , Alemanha , Humanos , Lactente , Recém-Nascido , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Recidiva , Estudos Retrospectivos , Espanha , Resultado do Tratamento , Tumor de Wilms/terapiaRESUMO
Therapeutic options for unresectable neuroendocrine carcinomas and relapsed or refractory solid tumors are still limited in pediatric patients. We present a retrospective review of 12 children (3 to 16 y) in a case series treated with a novel combination of oxaliplatin, irinotecan, and gemcitabine (triple therapy). We defined its feasibility in a mainly outpatient setting and assessed its toxicity and effectiveness. Three patients with unresectable neuroendocrine carcinomas received triple therapy as first-line treatment; 9 children with relapsed or refractory solid tumors of different entities were assigned after failure of standard treatment protocols. The treatment schedule comprised oxaliplatin (85 mg/m²), irinotecan (175 mg/m²), and gemcitabine (1,000 mg/m²), the latter to be repeated on day 8. A median of 7 cycles was applied. Nine of 12 patients showed hematotoxicity 0-III degrees. Gastrointestinal toxicity I-II degrees were handled satisfactorily by supportive drugs. Tumor response was defined as partial response in 1 of 12 children, stable disease in 8 of 12 children, and progressive disease in 3 of 12 children with a median time of disease control of 7 months. We regard triple therapy as a well-tolerated outpatient treatment option offering children a high quality of life and showing considerable effectiveness in delaying tumor progress.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Neuroendócrino/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia/tratamento farmacológico , Antimetabólitos Antineoplásicos/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma Neuroendócrino/patologia , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Irinotecano , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/patologia , Recidiva Local de Neoplasia/patologia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Compostos Organoplatínicos/administração & dosagem , Osteossarcoma/tratamento farmacológico , Osteossarcoma/secundário , Oxaliplatina , Estudos Retrospectivos , Resultado do Tratamento , GencitabinaRESUMO
INTRODUCTION: Alleviating pain is of high importance for children undergoing chemotherapy. Eutectic mixture of lidocain-prilocain cream (EMLA) is assumed to require 60 min application time. MATERIALS AND METHODS: We prospectively compared the pain during port-à-cath punctures after 40 min compared to 60 min of application time. A prospective, unblinded, cross-over study was performed. The children received two punctures during their chemotherapy protocol. Patients in group 1 had the first puncture after 40 min EMLA application time. Their second puncture (approximately a week later) was done after 60 min. Patients in group 2 started after 40 min. Pain was scored using the visual analogue scale (VAS) and the Bieri scale. Patients, parents and a nurse scaled the pain after the intervention. Eighty-seven children between 2 and 18 years with different malignant diseases were included. RESULTS AND DISCUSSION: On the VAS pain scale, the mean pain was 2.3 (minimum 0, maximum 9.2) after 40 min and 1.9 (minimum 0, maximum 9.4) after 60 min according to the observations of the nurse and very similarly according to the parents' observations. The children expressed more pain after 40 min of EMLA application time (mean pain, 3.5) and a significant pain reduction after 60 min application time (mean pain 1.7). CONCLUSION: In this study children experienced less pain after 60 min application time, but pain reduction was already seen after 40 min. The child's perception of pain differed from observers' point of view and should therefore always be included in pain management.
Assuntos
Anestésicos Locais/administração & dosagem , Cateterismo Periférico/efeitos adversos , Lidocaína/administração & dosagem , Percepção da Dor/efeitos dos fármacos , Dor/tratamento farmacológico , Prilocaína/administração & dosagem , Punções/efeitos adversos , Adolescente , Cateterismo Periférico/métodos , Criança , Pré-Escolar , Estudos Cross-Over , Tratamento Farmacológico/instrumentação , Feminino , Humanos , Combinação Lidocaína e Prilocaína , Masculino , Dor/etiologia , Medição da Dor/métodos , Limiar da Dor/efeitos dos fármacos , Estudos Prospectivos , Punções/métodos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Adolescents (aged 10-17 years) with acute lymphoblastic leukaemia (ALL) have unfavourable disease features and an inferior outcome when compared with younger children, but it is still unclear if differences in disease biology and prognosis exist between adolescents older or younger than 15 years. METHODS: We retrospectively analysed outcomes of 1094 adolescents with ALL, aged 10-17 years, treated within the AIEOP-BFM ALL 2000 trial, overall and by the age groups 10-14 and 15-17 years. FINDINGS: Compared with younger children (aged 1-9 years, n = 3647), adolescents had a statistically inferior 5-year event-free survival (EFS) [74.6% (1.3) vs. 84.4% (0.6)] and overall survival (OS) [83.4% (1.1) vs. 92.7% (0.4); p < 0.001]. Clinical and biological disease characteristics did not differ between the two subgroups of adolescents, including minimal residual disease (MRD) results during initial therapy, except for ETV6-RUNX1 frequency and gender. With a median follow-up of 8.8 years, the 5-year EFS and OS were 76.2% (1.5) and 84.9% (1.3), respectively, for those aged 10-14 years and 70.0% (2.8) and 78.8% (2.5) for those aged 15-17 years (p = 0.06; 0.05). There was no significant difference in the cumulative incidence of relapses [17.8% (1.4) and 18.3% (2.4); p = 0.98], while the incidence of treatment-related deaths as a first event was 2.6% (0.6) versus 7.4% (1.6) (p < 0.001) with, in particular, a higher incidence in the high-risk arm. INTERPRETATION: Further prospective studies and biological investigations are required to define optimal treatment for adolescents, in particular for those aged 15-17 years. Newer agents (immunotherapy, targeted therapy) in early treatment phases of patients at higher risk of treatment failure could replace most toxic treatment elements, with the aim of reducing both toxicity and the risk of relapses.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Neoplasia Residual , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Recidiva , Estudos RetrospectivosRESUMO
BACKGROUND: Until today, adult and pediatric clinical trials investigating single-agent or combinatorial HDAC inhibitors including vorinostat in solid tumors have largely failed to demonstrate efficacy. These results may in part be explained by data from preclinical models showing significant activity only at higher concentrations compared to those achieved with current dosing regimens. In the current pediatric trial, we applied an intra-patient dose escalation design. The purpose of this trial was to determine a safe dose recommendation (SDR) of single-agent vorinostat for intra-patient dose escalation, pharmacokinetic analyses (PK), and activity evaluation in children (3-18 years) with relapsed or therapy-refractory malignancies. RESULTS: A phase I intra-patient dose (de)escalation was performed until individual maximum tolerated dose (MTD). The starting dose was 180 mg/m2/day with weekly dose escalations of 50 mg/m2 until DLT/maximum dose. After MTD determination, patients seamlessly continued in phase II with disease assessments every 3 months. PK and plasma cytokine profiles were determined. Fifty of 52 patients received treatment. n = 27/50 (54%) completed the intra-patient (de)escalation and entered phase II. An SDR of 130 mg/m2/day was determined (maximum, 580 mg/m2/day). n = 46/50 (92%) patients experienced treatment-related AEs which were mostly reversible and included thrombocytopenia, fatigue, nausea, diarrhea, anemia, and vomiting. n = 6/50 (12%) had treatment-related SAEs. No treatment-related deaths occurred. Higher dose levels resulted in higher Cmax. Five patients achieved prolonged disease control (> 12 months) and showed a higher Cmax (> 270 ng/mL) and MTDs. Best overall response (combining PR and SD, no CR observed) rate in phase II was 6/27 (22%) with a median PFS and OS of 5.3 and 22.4 months. Low levels of baseline cytokine expression were significantly correlated with favorable outcome. CONCLUSION: An SDR of 130 mg/m2/day for individual dose escalation was determined. Higher drug exposure was associated with responses and long-term disease stabilization with manageable toxicity. Patients with low expression of plasma cytokine levels at baseline were able to tolerate higher doses of vorinostat and benefited from treatment. Baseline cytokine profile is a promising potential predictive biomarker. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01422499. Registered 24 August 2011.
Assuntos
Inibidores de Histona Desacetilases/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Vorinostat/administração & dosagem , Adolescente , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/farmacocinética , Humanos , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Masculino , Dose Máxima Tolerável , Análise de Sobrevida , Resultado do Tratamento , Vorinostat/efeitos adversos , Vorinostat/farmacocinéticaRESUMO
Introduction: Respiratory syncytial virus (RSV) and influenza virus infections are a significant healthcare risk for immunocompromised patients. In addition to community onset, nosocomial acquisition and transmission may also occur. Detection of asymptomatic shedders (e.g., patients in the incubation period or immunosuppressed long term shedders) facilitates control of nosocomial transmission. Methods: To strengthen the existing infection control concept, a PCR-based screening for RSV and influenza virus was implemented for all patients lacking respiratory symptoms (asymptomatic patients) who were hospitalized on an adult and a pediatric hemato-oncological ward. Laboratory results of this screening were analyzed retrospectively. Results: 665 respiratory specimens were obtained for screening from 251 patients (26% were 18 years and younger) from December 2016 to April 2017. In 23 patients without respiratory symptoms, either influenza virus or RSV infection was found, resulting in a detection rate of about 9%. In 6 patients, the infection was presumably detected during the incubation period, because an increase of viral load was observed in subsequent specimens. Positive screening results facilitated timely implementation of adequate infection control precautions. Nosocomial clusters of RSV or influenza were not detected during the screening period on the two wards. Conclusion: The seasonal screening program expanded our existing infection control concept in terms of patients lacking respiratory symptoms who shed influenza virus or RSV. It enabled us to identify 23 RSV or influenza infections in patients lacking respiratory symptoms in a 4-month period and thus to rapidly take isolation precautions.
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Anticorpos Biespecíficos , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Criança , Recidiva Local de Neoplasia/tratamento farmacológico , Anticorpos Biespecíficos/uso terapêutico , Intervalo Livre de Doença , Recidiva , Neoplasia Residual/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Indução de RemissãoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Asparaginase/administração & dosagem , Criança , Pré-Escolar , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Lactente , Masculino , Mercaptopurina/administração & dosagem , Metotrexato/administração & dosagem , Prednisona/administração & dosagem , Tempo , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Postoperative nausea and vomiting (PONV) occurs in every third patient undergoing general anesthesia without PONV prophylaxis. Antiemetic prophylaxis with dexamethasone is commonly used in patients at moderate risk. We present a case in which PONV prophylaxis with a single dose of dexamethasone led to tumor lysis in a patient with acute leukemia. In case of a cancer patient at moderate risk for PONV, the anesthesiologist should contact the oncologist first, or use other antiemetic drugs such as antiserotoninergic agents for PONV prophylaxis.
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Antieméticos/efeitos adversos , Dexametasona/efeitos adversos , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Síndrome de Lise Tumoral/etiologia , Criança , Humanos , Ácido Láctico/sangue , Masculino , Células Precursoras de Linfócitos BRESUMO
Fungal infections represent a life-threatening complication for patients receiving chemotherapy or undergoing hematopoietic stem cell transplantation. Historically, antifungal monotherapy is associated with a poor outcome. We treated three children with hematological malignancies and proven fungal infections (one cerebral mold infection, one disseminated Candida infection, one naso-pharyngeal mucor infection) with combination antifungal therapy plus granulocyte-colony-stimulation-factor-mobilized granulocyte transfusions as secondary prophylaxis during subsequent neutropenic episodes. With this approach, the fungal infection was effectively treated, and the anticancer therapy was completed without major delay. All children survived the fungal infection and the underlying malignancy. These experiences illustrate the feasibility of this approach using more than one antifungal agent together with immune-therapy in high-risk patients.
Assuntos
Antifúngicos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Granulócitos , Neoplasias Hematológicas/terapia , Transfusão de Leucócitos , Micoses/prevenção & controle , Adolescente , Aspergilose/prevenção & controle , Candidíase/prevenção & controle , Pré-Escolar , Terapia Combinada , Estudos de Viabilidade , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Mucormicose/prevenção & controle , Micoses/etiologia , Síndromes Mielodisplásicas/terapia , Neutropenia/complicações , Neutropenia/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapiaRESUMO
INTRODUCTION: In this retrospective, uncontrolled, observational study, the effect of granulocyte colony-stimulating factor (G-CSF)-stimulated granulocyte transfusions (GTX) in neutropenic paediatric patients with sepsis was evaluated. PATIENTS AND METHODS: Granulocytes were collected from unrelated, ABO group-matched and cytomegalic-antibody compatible donors. For neutrophil mobilization, donors received a single subcutaneous dose of glycosylated G-CSF (Lenograstim, Chugai Pharma, Japan) plus oral dexamethasone (8 mg). In total, 168 (range 1-19 per patient) GTX were transfused in 32 children with a median age of 7.4 (0.25 to 16) years. RESULTS: The underlying diseases comprised predominantly haematooncological malignancies (31 children). In 15 of 32 patients, neutropenia was related to allogeneic stem cell transplantation. All children suffered from sepsis based on international criteria (fever, tachycardia, respiratory rate >2 SD above normal in the context of a suspected or proven infection). In ten children bacteria were isolated, in six children a fungal infection was diagnosed and four sepsis episodes were caused by viral infections. GTX contained a median neutrophil number of 6.3 (range 1.9-13.9)x10(10) per transfusion and obtained a sustained haematological response after GTX. Nineteen out of 32 children survived the neutropenic sepsis, particularly nine out of 11 patients with bacterial sepsis. DISCUSSION: In contrast to the non-survivors, we observed a significant decrease in the C-reactive protein levels shortly after initiation of the GTX treatment in the surviving patients. A clear-cut benefit of GTX for children with neutropenic sepsis cannot be concluded from these data, but in children with (severe) bacterial sepsis refractory to antibiotic treatment, GTX were feasible, safe and could reduce mortality rates in this subgroup of patients.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Granulócitos/transplante , Transfusão de Leucócitos , Neutropenia/terapia , Sepse/terapia , Doença Aguda , Adolescente , Antineoplásicos/efeitos adversos , Biomarcadores/sangue , Remoção de Componentes Sanguíneos/métodos , Proteína C-Reativa/efeitos dos fármacos , Proteína C-Reativa/metabolismo , Criança , Pré-Escolar , Feminino , Seguimentos , Alemanha , Infecções por Bactérias Gram-Negativas/terapia , Infecções por Bactérias Gram-Positivas/terapia , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Granulócitos/efeitos dos fármacos , Granulócitos/metabolismo , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Leucemia Mieloide/terapia , Contagem de Leucócitos , Transfusão de Leucócitos/efeitos adversos , Transfusão de Leucócitos/métodos , Masculino , Micoses/terapia , Neutropenia/sangue , Neutropenia/induzido quimicamente , Neutropenia/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Proteínas Recombinantes , Estudos Retrospectivos , Sepse/sangue , Sepse/etiologia , Sepse/mortalidade , Análise de Sobrevida , Resultado do TratamentoRESUMO
In patients with iron overload, opportunistic infections are an underestimated risk. Yersinia enterocolitica is a rare organism to be isolated in this setting. The authors report a case of disseminated Y. enterocolitica sepsis in a 5-year-old boy with sideroblastic anemia. Ultrasound examination revealed massive ascites, a pseudo-appendicitis, and hypoechogenic lesions corresponding to abscess formations in the liver and spleen. The initial antibiotic therapy consisted of cefotaxime, gentamicin, and metronidazole, but only treatment with ciprofloxacin and meropenem led to defervescence and clinical stabilization. The risk of developing uncommon infections in patients with iron overload should be acknowledged by all physicians, and the relevance of ultrasound examination is emphasized. In this case, only a detailed history revealed that several days before the onset of diarrhea, the child was feeding a deer; this is how infection was probably acquired.