RESUMO
BACKGROUND/OBJECTIVES: Slow-flow vascular malformations are abnormal vessels that can lead to activation and consumption of coagulation factors and thrombosis, known as localized intravascular coagulopathy (LIC). Most clinical and research evidence of vascular malformation hemostasis relies on conventional coagulation studies, which may not provide a complete picture. Thromboelastograpy (TEG) is a tool that can provide real-time assessment of a patient's coagulation dynamics, and may allow for a more individualized treatment approach. We hypothesized that patients with slow-flow vascular malformations will have changes in TEG parameters peri-procedure that will help predict blood product or medication administration. DESIGN/METHODS: Institutional Review Board approved prospective study of patients with slow-flow vascular malformations undergoing a sedated, minor procedure. TEG and conventional coagulation studies were obtained preprocedure, 15 min, and when possible, at 30 min after the start of the procedure. RESULTS: Twenty-five patients were enrolled. Median age was 15 years (range 3-47 years). Procedures included laser and/or sclerotherapy. There were no changes in TEG parameters from baseline to 15 min or 30 min. The following decreased from baseline to 15 min: fibrinogen 313 to 287 mg/dL (P = .001), D-dimer 1.3 to 1.1 mg/L (P = .02), hemoglobin 12.8 to 11.8 g/dL (P = .001), and platelet count 272 000 to 256 000 (P = .006). No patient had a bleeding/thrombotic complication during or within 1 week postprocedure. CONCLUSION: We saw no change in TEG parameters or bleeding or clotting complications despite significant numerical changes in conventional coagulation profiles, suggesting that conventional studies may not be as useful in determining risks of bleeding or thrombotic complications peri-procedure for minor procedures.
Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Hemostasia/fisiologia , Escleroterapia/métodos , Tromboelastografia/métodos , Malformações Vasculares/terapia , Adolescente , Adulto , Coagulação Sanguínea/fisiologia , Testes de Coagulação Sanguínea , Velocidade do Fluxo Sanguíneo/fisiologia , Criança , Pré-Escolar , Feminino , Hemorragia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Vascular malformations (VM) are congenital lesions that can be debilitating and cause significant aesthetic and functional limitations. The chemotherapeutic agent bleomycin has been utilized as a sclerosant, directly injected percutaneously into the VM. Unfortunately, little is known about the benefits and short-term side effects of bleomycin with intralesional injections. PROCEDURE: An IRB approved, retrospective chart review was performed on patients with VM who had been treated with intralesional bleomycin. Data included type of VM, number of treatments, total bleomycin dose per m², and adverse effects. A questionnaire was administered to available patients to assess subjective outcomes and side effects. RESULTS: Forty-six patients were treated with 141 procedures of bleomycin sclerotherapy for VM. Patient ages ranged from 1 to 20 years (median age 10 years). The median cumulative bleomycin dose was 16.3 units/m²/person (range of 1.7-97.0 units/m²/person). Sixty-three percent of patients were reached for a questionnaire to assess short-term side effects. Ninety percent of patients surveyed were satisfied to very satisfied with the results from the procedure. About 24% of patients experienced transient nausea, vomiting and/or local hyperpigmentation. CONCLUSION: Bleomycin sclerotherapy can be an effective treatment of VM with repeat exposure with minor risk of short-term side effects, however, long-term risks are of great concern. Further studies are required to assess systemic absorption and long-term risks.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Bleomicina/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medidas de Resultados Relatados pelo Paciente , Escleroterapia , Malformações Vasculares/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
KIT receptor tyrosine kinase mutations are implicated as a prognostic factor in adults with core binding factor (CBF) acute myeloid leukemia (AML). However, their prevalence and prognostic significance in pediatric CBF AML is not well established. We performed KIT mutational analysis (exon 8 and exon 17) on diagnostic specimens from 203 pediatric patients with CBF AML enrolled on 4 pediatric AML protocols. KIT mutations were detected in 38 (19%) of 203 (95% CI, 14%-25%) patient samples of which 20 (52.5%) of 38 (95% CI, 36%-69%) involved exon 8, 17 (45%) of 38 (95% CI, 29%-62%) involved exon 17, and 1 (2.5%; 95% CI, 0%-14%) involved both locations. Patients with KIT mutations had a 5-year event-free survival of 55% (+/- 17%) compared with 59% (+/- 9%) for patients with wild-type KIT (P = .86). Rates of complete remission, overall survival, disease-free survival, or relapse were not significantly different for patients with or without KIT mutations. Location of the KIT mutation and analysis by cytogenetic subtype [t(8;21) vs inv(16)] also lacked prognostic significance. Our study shows that KIT mutations lack prognostic significance in a large series of pediatric patients with CBF AML. This finding, which differs from adult series and a previously published pediatric study, may reflect variations in therapeutic approaches and/or biologic heterogeneity within CBF AML. Two of 4 studies included in this analysis are registered at http://clinicaltrials.gov as NCT00002798 (CCG-2961) and NCT00070174 (COG AAML03P1).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fatores de Ligação ao Core/genética , Leucemia Mieloide Aguda , Proteínas Proto-Oncogênicas c-kit/genética , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Éxons/genética , Feminino , Predisposição Genética para Doença/genética , Humanos , Lactente , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Mutação , Prevalência , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Translocação Genética , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Patients receiving myelosuppressive chemotherapy remain at increased risk for developing febrile neutropenia (FN). For this heterogeneous population, a biomarker based risk stratification of FN patients may be a useful clinical tool. We hypothesized that serum biomarkers during initial presentation of an FN event could be predictive of subsequent clinical outcome. PROCEDURE: Eighty-nine FN events from 36 non-consecutive subjects were analyzed. "High-risk" FN criteria included prolonged hospitalization (≥ 7 days), admission to pediatric intensive care unit (PICU) or a microbiology confirmed bacteremia. Patients with "low risk" FN had none of the above. Biomarkers measured during the first 2 days of FN hospitalization were analyzed and correlated with respective clinical outcome. RESULTS: Of the 89 FN events, 44 (49%) fulfilled pre-defined high-risk criteria and 45 (51%) were low-risk. Procalcitonin level (>0.11 ng/ml) was found to be associated with the high-risk FN outcome with sensitivity of 97%. With an increase in log scale by 1, the odds of being high-risk FN increased twofold. Hs-CRP >100 mg/L had sensitivity of 88% in predicting high-risk FN. The odds of a high-risk FN event increased by approximately 1.8-fold with an increase in the log scale of hs-CRP by 1 (10-fold). In univariate analysis, IL-6, IL-8, and IL-10 were statistically significant and associated with high-risk FN. However, no statistically significant difference was found for IL-1α, sIL-2Ra, IL-3, or TNF-α. CONCLUSIONS: Biomarkers with appropriate critical threshold values may be a useful clinical tool for appropriate risk stratification of children with FN.
Assuntos
Biomarcadores/análise , Neoplasias/complicações , Neutropenia/etiologia , Adolescente , Adulto , Calcitonina/sangue , Peptídeo Relacionado com Gene de Calcitonina , Criança , Pré-Escolar , Feminino , Hospitalização , Humanos , Lactente , Unidades de Terapia Intensiva , Interleucina-10/sangue , Interleucina-3/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Neoplasias/tratamento farmacológico , Neutropenia/tratamento farmacológico , Projetos Piloto , Prognóstico , Estudos Prospectivos , Precursores de Proteínas/sangue , Curva ROC , Fatores de Risco , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
Myeloid sarcomas are rare extramedullary tumors composed of immature myeloid cells. Most cases are seen in childhood acute myelogenous leukemia (AML). They can develop at many sites, but cardiac involvement is a rare finding. We report the case of a 24-year-old woman who, after being in remission from AML for 10 years, developed an isolated cardiac myeloid sarcoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Neoplasias Cardíacas/terapia , Sarcoma Mieloide/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ecocardiografia , Evolução Fatal , Feminino , Seguimentos , Neoplasias Cardíacas/diagnóstico , Humanos , Imageamento por Ressonância Magnética , Indução de Remissão , Sarcoma Mieloide/diagnóstico , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
Pharmacogenomics (PGx) is a growing field within precision medicine. Testing can help predict adverse events and sub-therapeutic response risks of certain medications. To date, the US FDA lists over 280 drugs which provide biomarker-based dosing guidance for adults and children. At Arkansas Children's Hospital (ACH), a clinical PGx laboratory-based test was developed and implemented to provide guidance on 66 pediatric medications for genotype-guided dosing. This PGx test consists of 174 single nucleotide polymorphisms (SNPs) targeting 23 clinically actionable PGx genes or gene variants. Individual genotypes are processed to provide per-gene discrete results in star-allele and phenotype format. These results are then integrated into EPIC- EHR. Genomic indicators built into EPIC-EHR provide the source for clinical decision support (CDS) for clinicians, providing genotype-guided dosing.
RESUMO
Bleeding is a common event in many people, but when is it abnormal and when should further evaluation and diagnostic testing be performed? This review will highlight the three most common bleeding disorders and briefly describe their more common forms of presentation and management options. We will also discuss the role of local hemophilia treatment centers in assisting physicians around the state in managing these complex patients.
Assuntos
Hematologia , Hemofilia A/terapia , Doenças de von Willebrand/diagnóstico , Doenças de von Willebrand/terapia , Arkansas , Hospitais Pediátricos , HumanosRESUMO
There are few data regarding the use of enoxaparin in children undergoing myelosuppressive therapy for malignancies even though thrombosis is a known risk in pediatric patients with malignancies. Low-molecular-weight heparin such as enoxaparin has become widely used in adult patients with thrombosis. The purpose of this study was to review the utilization of low-molecular-weight heparin, enoxaparin (Lovenox), in children with cancer at our institution who had thrombosis while undergoing myelosuppressive chemotherapy. In particular we were interested in the efficacy of enoxaparin in these patients, and in whether these children were able to continue their chemotherapy without adjustment or interruption secondary to bleeding complications. We conducted a retrospective review from 1999 through April 1, 2004. Seven patients (4-17 years of age) were identified. Diagnosis included B-precursor acute lymphoblastic leukemia (ALL) (n=three), T-ALL, Hodgkin's disease, anaplastic large cell lymphoma, and rhabdomyosarcoma (n=one each). Six patients had a deep vein thrombus (DVT) or clot of the vena cava. One of these six patients also had a pulmonary embolus. One patient presented with manifestations of a unilateral cerebral vascular accident without evidence of DVT. Most patients were screened for known hypercoaguable abnormalities. Treatment was enoxaparin, 1-1.5 mg/kg/dose twice daily to maintain a heparin anti-Xa level of 0.5-1.5 IU/mL till clot resolution. The dose was then decreased to daily for a total of 3-6 months of therapy. All patients had resolution of their thrombosis within 1-2 months of initiation of enoxaparin, and none required delays or dose reduction of their chemotherapy regimens while on anticoagulation, though some were supported by blood and platelet transfusions. Enoxaparin was safely administered to this series of seven patients for thrombotic complications in children undergoing cancer chemotherapy.
Assuntos
Enoxaparina/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Trombose Venosa/complicações , Trombose Venosa/tratamento farmacológico , Adolescente , Transtornos da Coagulação Sanguínea/complicações , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Neoplasias/patologia , Estudos Retrospectivos , Trombose Venosa/patologiaRESUMO
The outcome for children with acute megakaryoblastic leukemia (AMKL) remains poor, except for cases associated with Down syndrome (DS). This study compared immunophenotypic and drug sensitivity patterns of childhood AMKL cases with or without DS. All DS-AMKL cases showed high expression of CD36 and were very sensitive to cytarabine and daunorubicin in vitro. In children without DS, high expression of CD36 on AMKL blasts identified a sub-group with immunophenotypic and drug sensitivity patterns similar to that of DS AMKL. Among non-DS AMKL patients, CD36-high cases had a superior outcome compared with CD36-negative cases. CD36 expression in acute myeloid leukemia cases other than AMKL was not associated with increased in vitro drug sensitivity. CD36 expression in AMKL may be an indicator of megakaryoblast maturation and chemotherapy sensitivity.
Assuntos
Antígenos CD36/biossíntese , Regulação Neoplásica da Expressão Gênica , Leucemia Megacarioblástica Aguda/complicações , Leucemia Megacarioblástica Aguda/metabolismo , Adolescente , Adulto , Biomarcadores Tumorais , Membrana Celular/metabolismo , Criança , Pré-Escolar , Citarabina/farmacologia , Daunorrubicina/farmacologia , Síndrome de Down/complicações , Humanos , Imunofenotipagem , Lactente , Recém-Nascido , Leucemia Megacarioblástica Aguda/patologia , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
The majority of Osteosarcoma (OS) patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. These protocols include distraction osteogenesis (DO), which is characterized by direct new bone formation. Cisplatin (CDP) is extensively used for OS chemotherapy and recent studies, using a mouse DO model, have demonstrated that CDP has profound negative effects on bone repair. Recent oncological therapeutic strategies are based on the use of standard cytotoxic drugs plus an assortment of biologic agents. Here we demonstrate that the previously reported CDP-associated inhibition of bone repair can be modulated by the administration of a small molecule p53 inducer (nutlin-3). The effects of nutlin-3 on CDP osteotoxicity were studied using both pre- and post-operative treatment models. In both cases the addition of nutlin-3, bracketing CDP exposure, demonstrated robust and significant bone sparing activity (p < 0.01-0.001). In addition the combination of nutlin-3 and CDP induced equivalent OS tumor killing in a xenograft model. Collectively, these results demonstrate that the induction of p53 peri-operatively protects bone healing from the toxic effects of CDP, while maintaining OS toxicity. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1716-1724, 2016.
Assuntos
Antineoplásicos/uso terapêutico , Regeneração Óssea/efeitos dos fármacos , Cisplatino/uso terapêutico , Imidazóis/uso terapêutico , Osteossarcoma/tratamento farmacológico , Piperazinas/uso terapêutico , Animais , Feminino , Humanos , Imidazóis/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Osteogênese por Distração , Osteossarcoma/cirurgia , Piperazinas/farmacologia , Distribuição Aleatória , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: To determine dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of a protracted, intermittent schedule of daily 30-minute infusions of topotecan (TPT) for up to 12 consecutive days, every 3 weeks, in children with refractory leukemia. PATIENTS AND METHODS: Forty-nine children were enrolled onto this phase I trial (24 with acute nonlymphoblastic leukemia [ANLL] and 25 with acute lymphoblastic leukemia [ALL]). TPT dosage was escalated from 2.0 to 5.2 mg/m(2)/d for 5 days and 2.4 mg/m(2)/d from 7 days to the same dose for 9 and 12 days in cohorts of three to six patients when no DLT was identified. TPT pharmacokinetics were studied in 33 children once or twice (first and last doses in patients who received TPT for > 7 days). RESULTS: Seventy assessable courses of TPT were administered to 49 children who had refractory leukemia. DLTs were typhlitis, diarrhea, and mucositis, and the MTD was 2.4 mg/m(2)/d for 9 days in this group of heavily pretreated children. In 33 patients, the median TPT lactone clearance after the first dose was 19.2 L/h/m(2) (range, 9.4 to 45.9 L/h/m(2)) and did not change during the course. There were significant responses (one complete response [CR] and four partial responses [PR] in patients with ANLL and one CR and two PRs in patients with ALL), and all but one were at dosages of TPT given for at least 9 days. CONCLUSION: The MTD was 2.4 mg/m(2)/d for 9 days. Further testing is warranted of TPT's schedule dependence in children with leukemia.
Assuntos
Antineoplásicos/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Topotecan/administração & dosagem , Adolescente , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Lactente , Infusões Intravenosas , Masculino , Topotecan/efeitos adversos , Topotecan/farmacocinética , Topotecan/farmacologia , Resultado do TratamentoAssuntos
Dor Abdominal/etiologia , Lesão Pulmonar Aguda/diagnóstico , Anemia Aplástica/diagnóstico , Diarreia Infantil/etiologia , Entamebíase/diagnóstico , Listeriose/diagnóstico , Abscesso Hepático/diagnóstico , Transfusão de Plaquetas/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Diagnóstico Diferencial , Humanos , Lactente , Masculino , Infecções Oportunistas/diagnósticoRESUMO
Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non-cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five-dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p < 0.001). Further, no significant inhibitory effects from the five-dose CDP regimen were observed in TNFR1KO mice. The two-dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri-operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP.
Assuntos
Antineoplásicos/toxicidade , Regeneração Óssea/efeitos dos fármacos , Cisplatino/toxicidade , Osteogênese por Distração , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Animais , Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator de Necrose Tumoral alfa/metabolismoRESUMO
PURPOSE: To determine the outcomes, with particular attention to toxicity, of children with Down syndrome (DS) and acute myeloid leukemia (AML) treated on Pediatric Oncology Group (POG) protocol 9421. PATIENTS AND METHODS: Children with DS and newly diagnosed AML (n = 57) were prospectively enrolled onto the standard-therapy arm of POG 9421 and were administered five cycles of chemotherapy, which included daunorubicin 135 mg/m(2) and mitoxantrone 80 mg/m(2). Outcomes and toxicity were evaluated prospectively and were compared with the non-DS-AML cohort (n = 565). A retrospective chart review was performed to identify adverse cardiac events. RESULTS: In the DS-AML group, 54 patients (94.7%) entered remission. One experienced induction failure and two died. Of the 54 who entered remission, three relapsed and six died as a result of other causes. The remission induction rate was similar in the non-DS-French-American-British (FAB) M7 (91.7%) and non-DS-non-M7 (89.3%) groups. The 5-year overall survival was significantly better in the DS-AML group (78.6%) than in the non-DS-M7 (36.3%) or the non-DS-non-M7 (51.8%) groups (P < .001). No age-related difference in 5-year, event-free survival was seen between patients younger than 2 years (75.8%) and those aged 2 to 4 years (78.3%). Symptomatic cardiomyopathy developed in 10 patients (17.5%) with DS-AML during or soon after completion of treatment; three died as a result of congestive heart failure. CONCLUSION: The POG 9421 treatment regimen was highly effective in both remission induction and disease-free survival for patients with DS-AML. However, there was a high incidence of cardiomyopathy, which supports current strategies for dose reduction of anthracyclines in this patient population.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cardiomiopatias/induzido quimicamente , Síndrome de Down/complicações , Coração/efeitos dos fármacos , Leucemia Mieloide/tratamento farmacológico , Doença Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Daunorrubicina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Mitoxantrona/administração & dosagem , Estudos Prospectivos , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: There is considerable variation in the use of HLA-matched related bone marrow transplantation (BMT) for the treatment of pediatric patients with newly diagnosed acute myeloid leukemia (AML). Some oncologists have argued that BMT should be offered to most patients in first complete remission (CR). Others have maintained that transplantation in first remission should be reserved for patients with high-risk disease. We performed this study to determine how disease risk influences the efficacy of BMT. METHODS: We combined data from four cooperative group clinical trials: Pediatric Oncology Group 8821, Children's Cancer Group (CCG) 2891, CCG 2961, and Medical Research Council 10. Using cytogenetics and the percentage of marrow blasts after the first course of chemotherapy, patients were stratified into favorable, intermediate, and poor-risk disease groups. Patients who could not be risk classified were analyzed separately. Outcomes for patients assigned to BMT and for patients assigned to chemotherapy alone were compared. RESULTS: The data set included 1,373 pediatric patients with AML in first CR. In the intermediate-risk group, the estimated disease-free survival at 8 years for patients who did not undergo transplantation was 39% +/- 5% (2 SE), whereas it was 58% +/- 7% for BMT patients. The estimated overall survival for patients who did not undergo transplantation was 51% +/- 5%, whereas it was 62% +/- 7% for BMT patients. Both differences were significant (P < .01). There were no significant differences for survival in the other two risk groups or in the non-risk-stratified patients. CONCLUSION: Our study indicates that HLA-matched related BMT is an effective treatment for pediatric patients with intermediate-risk AML in first CR.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Antígenos HLA/análise , Teste de Histocompatibilidade , Leucemia Mieloide Aguda/cirurgia , Criança , Intervalo Livre de Doença , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/mortalidade , Modelos de Riscos Proporcionais , Recidiva , Indução de Remissão , Medição de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
Achieving hemostasis in patients with hemophilia A or B is complicated by the presence of inhibitors and is made even more difficult when these individuals require surgery. Over a 4-year period, 6 patients with inhibitors to factor VIII and 1 patient with inhibitors to factor IX underwent surgery or invasive procedures at our institution. A total of 26 procedures were performed, primarily using the bypassing agent FEIBA for bleeding control. Excellent hemostasis was obtained in all cases, adding to accumulating data indicating that FEIBA is safe and effective in hemophilia patients with inhibitors who require surgery.
Assuntos
Inibidores dos Fatores de Coagulação Sanguínea/sangue , Fatores de Coagulação Sanguínea/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Hemofilia A/cirurgia , Hemofilia B/cirurgia , Hemostasia Cirúrgica , Adolescente , Adulto , Pré-Escolar , Hemofilia A/sangue , Hemofilia B/sangue , Hemostasia/efeitos dos fármacos , Humanos , Lactente , MasculinoRESUMO
Children with Down syndrome (DS) with acute megakaryocytic leukemia (AMkL) have very high survival rates compared with non-DS AMkL patients. Somatic mutations identified in the X-linked transcription factor gene, GATA1, in essentially all DS AMkL cases result in the synthesis of a shorter (40 kDa) protein (GATA1s) with altered transactivation activity and may lead to altered expression of GATA1 target genes. Using the Affymetrix U133A microarray chip, we identified 551 differentially expressed genes between DS and non-DS AMkL samples. Transcripts for the bone marrow stromal-cell antigen 2 (BST2) gene, encoding a transmembrane glycoprotein potentially involved in interactions between leukemia cells and bone marrow stromal cells, were 7.3-fold higher (validated by real-time polymerase chain reaction) in the non-DS compared with the DS group. Additional studies confirmed GATA1 protein binding and transactivation of the BST2 promoter; however, stimulation of BST2 promoter activity by GATA1s was substantially reduced compared with the full-length GATA1. CMK sublines, transfected with the BST2 cDNA and incubated with HS-5 bone marrow stromal cells, exhibited up to 1.7-fold reduced cytosine arabinoside (ara-C)-induced apoptosis, compared with mock-transfected cells. Our results demonstrate that genes that account for differences in survival between DS and non-DS AMkL cases may be identified by microarray analysis and that differential gene expression may reflect relative transactivation capacities of the GATA1s and full-length GATA1 proteins.
Assuntos
Síndrome de Down/genética , Fator de Transcrição GATA1/genética , Leucemia Megacarioblástica Aguda/tratamento farmacológico , Leucemia Megacarioblástica Aguda/genética , Criança , Análise por Conglomerados , Citarabina/toxicidade , Primers do DNA , Síndrome de Down/complicações , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Megacarioblástica Aguda/complicações , Luciferases/genética , Hibridização de Ácido Nucleico , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Células Tumorais CultivadasRESUMO
Relapse is a major obstacle in the cure of acute myeloid leukemia (AML). The Pediatric Oncology Group AML Study 9421 tested 2 different strategies to improve event-free survival (EFS) and overall survival (OS). Patients were randomized to receive standard-dose DAT (daunorubicin, cytarabine, and thioguanine) or high-dose DAT during induction. To interfere with P-glycoprotein (P-gp)-dependent drug efflux, the second randomization tested the benefit of cyclosporine (CsA) added to consolidation chemotherapy. Of the 282 children randomly assigned to receive standard DAT induction, 248 (87.9%) achieved remission compared to 253 (91%) of the 278 receiving high-dose DAT (P = ns). Children with HLA-identical sibling donors who achieved a complete remission received an allogeneic bone marrow transplant as consolidation. For the 83 patients receiving a matched related donor bone marrow transplantation (BMT), the 3-year disease-free survival (DFS) is 67%. Of the 418 children who achieved remission and went on to consolidation with and without CsA, the DFS was 40.6% and 33.9%, respectively (P = .24). Overexpression of P-gp was infrequent (14%) in this pediatric population. In this study, intensifying induction with high-dose DAT and the addition of CsA to consolidation chemotherapy did not prolong the durations of remission or improve overall survival for children with AML.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclosporina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Criança , Pré-Escolar , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Imunossupressores/uso terapêutico , Lactente , Cariotipagem , Contagem de Leucócitos , Masculino , Mitolactol/administração & dosagem , Indução de Remissão , Análise de Sobrevida , Tamoxifeno/administração & dosagem , Resultado do TratamentoRESUMO
Patients with Langerhans cell histiocytosis (LCH) may behave differently depending on what sites are involved and the response or lack of response to earlier therapies. Therapy for high-risk patients or those with multiple reactivations continues to be challenging because of variable response rates and frequent toxicities. The goals of this study were to determine the long-term disease free survival in children with high-risk or multiply reactivated LCH treated with 2-CDA, and the toxicity of low dose continuous infusion (CI). Ten children with multiple reactivations or high-risk disease as defined by the Histiocyte Society were treated with CI 2-CDA and were evaluable for response and toxicity assessment. The starting dose of 2-CDA was 5 mg/M(2)/day for 3 days and escalated to 6.5 mg/M(2)/day for 3 days if tolerated. The maximum number of courses of 2-CDA per patient was limited to six. Fifty-two courses of 2-CDA were administered without difficulty. After the patient demonstrated no acute toxicity with the first administration of 2-CDA, the subsequent doses were given at home to all but one patient. All 10 patients had a clinical response, 9 documented by radiographic, or changes in physical exam or review of systems. Toxicity was limited to myelosuppression. Seven of the 10 patients required no additional therapy and remain disease free a median of 50 months from completing therapy. The three remaining patients are currently disease free after receiving other therapy. Further studies are needed to determine the role of 2-CDA in this patient population. 2-CDA can be given safely using home therapy, and may effective even in high-risk patients.