ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Acute myelogenous leukemia (AML) is the second most common leukemia in children, with ∼400 new cases occurring annually in the United States. Worldwide, the highest rates of childhood AML occur in Asia and the lowest rates are reported from India and South America.Numerous genetic risk factors for childhood AML have been defined, including Down syndrome, neurofibromatosis, and Fanconi anemia. Research into environmental risk factors has been limited by the rarity of this disease; however, studies of AML in adults have implicated ionizing radiation, solvents, and petroleum products as potential etiologic agents. The largest analytic study of childhood AML found that occupational exposures of either parent to pesticides, paternal exposure to petroleum products, and postnatal exposures to pesticides are increased in children with AML. In addition, maternal use of marijuana during pregnancy was associated with an increased risk of AML, especially the monocytic subtypes. Further study of childhood AML, including occurrence of the disease as a second malignancy, is needed in order to confirm these findings and to increase our understanding of this leukemia.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

In recent years, our understanding of normal human hematopoiesis has expanded greatly. We have increased our knowledge of regulatory growth factors, the receptors through which they act, and the secondary messengers involved in transducing the growth/differentiation signals from the cytoplasmic membrane to the nucleus. This knowledge has revealed potential mechanisms for inducing the neoplastic transformation of hematopoietic cells. This applies in particular to the role of viral oncogenes and cellular protooncogenes and, more recently, to the role of tumor suppressor genes. Protooncogenes are intimately involved in the processes of cell proliferation and differentiation. Therefore, any amplification, mutation, structural alteration, or change in transcriptional regulation of protooncogenes might lead to or be associated with induction of the malignant phenotype. Based on the importance of these genes in leukemogenesis and the maintenance of the malignant phenotype, it seems reasonable to hypothesize that targeted disruption of leukemogenic genes may be of therapeutic value.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The acute myelogenous leukemias (AMLs) are a heterogeneous group of disorders with diverse morphologic, histochemical, and antigenic characteristics. In this article, we discuss the heterogeneous nature of AML with regard to its cellular level of origin, cell surface antigen expression, and hematopoietic growth factor responsiveness.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Techniques to assay minimal residual disease are available for most patients with acute lymphoblastic leukemia, non-Hodgkin's lymphoma, breast cancer, Ewing's sarcoma, and others. Today, a few such tests exist for acute myelogenous leukemia (AML). This review evaluates the tests available for assessing minimal residual disease in AML: morphology, growthin vitro, cytogenetics, magnetic resonance imaging, polymerase chain reaction (PCR)-based assays for translocation products, and multiparameter flow cytometry. Of these, multiparameter flow cytometry appears most promising. Studies using multiparameter flow cytometry to identify leukemic cells by aberrant antigen expression have reported a high positive predictive value with regard to the incidence of relapse. In addition, the test is specific, rapid, inexpensive, and applicable to a sufficiently broad group of patients, allowing its use outside of the research laboratory setting. Judicious use of some of the available assays singly or in combination should identify patients harboring residual leukemic cells.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

PurposeCyclophosphamide is commonly used in the treatment of children with malignant brain tumors. The purpose of this study was to develop a multicycle, high-dose intensity cyclophosphamide regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) and to assess its activity against malignant glioma and primitive neuroectodermal tumor (PNET).MethodsTwenty-three patients with brain tumors, including 15 with malignant glioma and six with PNET, were enrolled. Cyclophosphamide (1.8–2.25 g/m2/day for 2 days i.v.; total dose 3.6–4.5 g/m2) was administered and was followed by recombinant human GM-CSF (5 μg/kg/day s.c.) on days 3–11 or until the absolute granulocyte count reached 1.5 x 109/L.ResultsWith a total of 83 cycles administered, the mean dose intensity of cyclophosphamide ranged from 1.5 g/m2/week through cycle 2 (22 patients) to 0.8 g/m2/week through cycle 8 (two patients). No activity was seen against malignant glioma, and five of six patients with PNET had partial responses. The mean duration of a neutrophil count of <0.5 x 109/L was only 8 days; the platelet recovery was substantially longer. Fever during neutropenia occurred in 54 of 83 cycles. One patient died from transfusion-related graft-versus-host disease.ConclusionsA cyclophosphamide regimen equal to twice the dose intensity of that used in conventional therapy was administered. The regimen was active against PNET but inactive against malignant glioma.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

PurposeSeven children with newly diagnosed acquired severe aplastic anemia (SAA) were treated with a combination of long-term granulocyte-macrophage colony-stimulating factor (GM-CSF) and immunosuppression to assess the potential for GM-CSF to induce sustained neutrophil recovery, reduce the incidence of infection, and enhance the therapeutic efficacy of immuno-suppression.MethodsPatients received a 14-day course of i.v. antithymocyte globulin 15 mg/kg/day with oral prednisone 1 mg/kg/day, long-term daily oral cyclosporine A 10 mg/kg/day, and long-term daily s.c. GM-CSF 5 μg/kg/day.ResultsAll seven children recovered an absolute neutrophil count of >1.0 x 109/L within 3.5 months of diagnosis (mean 60 days). Of the six children followed throughout their entire illness (follow-up 10–27 months), five are platelet and red cell transfusion independent (three off-therapy, two on tapering therapy) and one continues on therapy with a diminishing transfusion requirement. Compared with seven children treated previously with immuno-suppression alone, children who received GM-CSF spent fewer days in the hospital and were less likely to develop infection.ConclusionsThe addition of GM-CSF to immunosuppressive therapy appears to be beneficial in the treatment of children with acquired SAA with GM-CSF stimulating granulopoiesis. The children are better protected from infectious complications while immunosuppressive agents achieve full therapeutic potential.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

PurposeTo determine whether the addition of dexamethasone to ondansetron (OND + DEX) is a more effective antiemetic regimen than ondansetron (OND) alone in children receiving chemotherapy.Patients and MethodsChildren who had solid tumors and who were receiving highly emetogenic chemotherapy, including cisplatin, carboplatin, cyclophosphamide, and ifosfamide, were randomized (1:1) in a double-blind fashion to receive either OND 0.15 mg/kg intravenously (i.v.) 30 min before and 4 and 8 h after chemotherapy and placebo, or OND + DEX (same OND doses plus DEX 8 mg/m2i.v. 30 min before chemotherapy, followed by 16 mg/m2in divided doses) as antiemetics. The patients were crossed over to the other antiemetic regimen when receiving an identical course of chemotherapy. Patients were monitored for emetic episodes, nausea, appetite, sense of well-being, and antiemetic adverse events.ResultsA total of 33 patients were evaluated. Sixty-one percent of the patients receiving OND + DEX regimens had a complete response for emetic episodes as compared with 23% with OND alone. Combined complete and major responses (two or less emetic episodes) were 86% for OND + DEX and 67% for OND. Failure for emetic episodes (more than five vomitings/day) were seen only in 7–10% of the total population. Minimal or no nausea was experienced in 74% of OND + DEX courses and in 52% of the OND courses. Appetite was better in OND + DEX courses (p = 0.006). Both antiemetic arms had similar adverse events. Mild to moderate sedation occurred in about half of the courses, followed by restlessness (20%), headache (17%), diarrhea (17%), and hiccups (2%).ConclusionThe combination of ondansetron and dexamethasone is superior to ondansetron alone to control emetic episodes in children receiving highly emetogenic chemotherapy (p = 0.04).

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Purposeα-Hemolytic streptococcal (AHS) sepsis is increasing in oncology patients receiving myelosuppressive chemotherapy. In response to a high rate of AHS sepsis in this population at our institution, an oral care protocol was instituted, including vancomycin 0.5% in flavored methylcellulose (vanc paste) applied orally t.i.d. at the oncologists' discretion.Patients and MethodsA retrospective cohort study of 239 neutropenic episodes among 42 children receiving myelosuppressive chemotherapy between 1988 and 1991 compared the incidence of septicemia based on the prophylactic use of vanc paste.ResultsA total of 236 consecutive neutropenic episodes were evaluable, 121 with vanc paste and 115 without. AHS sepsis occurred in one child using vanc paste and in six children not using vanc paste (p = 0.06). Excluding staph-only positive blood cultures, which would not be reduced with a topical oral antibiotic drug, there were 6 and 13 positive blood cultures in the vanc-paste and nonvanc-paste patients, respectively (p = 0.09). There was no increase in incidence of gram-negative bacteremia among vanc-paste recipients. Vancomycin resistance was not encountered.ConclusionThis analysis suggests that vanc paste effectively reduces AHS sepsis, does not increase gram-negative bacteremia, and is not associated with vancomycin resistance. A multicentered, placebo-controlled, double-blind study is currently planned.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

PurposeLittle information is available that documents the incidence and possible etiology of a prolonged thrombin time (TT) found in children with nephrotic syndrome. We speculated that this prolonged TT might best be explained by an altered fibrinogen similar to that found in the newborn.Patients and MethodsWe describe 20 children with nephrosis, an unexplained prolonged TT and reptilase time (RT), and an elevated fibrinogen level. Thrombin and/or plasmin effect on plasma fibrinogen was studied by analyzing for soluble monomer, D-dimer, fibrin degradation products, Bβ 1–42 peptide, and by polyacrylamide gel electrophoresis (PAGE) and agarose electrophoresis. Structural changes in the fibrinogen molecule were investigated using two- dimensional gel (2D gel) electrophoresis. Fibrinogen was purified via glycine precipitation, and the sialic acid (SA) content was determined.ResultsNo evidence for in vivo thrombin and/or plasmin effect on fibrinogen could be detected in 13 of 20 children tested. Additionally, no fibrin/fibrinogen degradation products or soluble fibrin complexes were detected using PAGE or agarose electrophoresis in this group of patients. The Bβ isoforms of nephrosis fibrinogen were similar in isoelectric point on 2D gel electrophoresis to those of fetal fibrinogen and demonstrated a greater electronegative shift when compared with normal adult fibrinogen. Also, the SA content of nephrosis and fetal fibrinogen were greater than that measured in adult fibrinogen. Both nephrosis and fetal fibrinogen were more resistant to neuraminidase treatment than was normal adult fibrinogen.ConclusionsThese data support the notion that an altered fibrinogen exists in some children with nephrotic syndrome characterized by an increased TT and RT, elevated fibrinogen, and both an increased negative charge and SA content.

ISSN:1077-4114    

出版商:OVID    

年代:1995

数据来源: OVID