ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID

ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Purpose: The in vitro and in vivo efficacy of a single dose of asparaginase in children with newly diagnosed acute lymphoblastic leukemia and the correlation between in vitro and in vivo antileukemic response and long-term outcome were prospectively evaluated.Patients and Methods: Two hundred fifty-one patients were randomized to receive 1 of 3 asparaginase preparations (Eschcrichia coli. Erwinia chrysanthemi [Erwinia], or pegaspargase). In vitro assessment of efficacy was expressed as the percent total cell kill (TCK). based on the number of viable cells found after 5 days of culture in the presence of asparaginase. In vivo leukemia cell kill (LCK) was calculated by comparing bone marrow cellularity and percent leukemic blasts in marrow obtained before and 5 days after treatment with a single dose of asparaginase. Acute toxicity was determined by clinical and laboratory assessment.Results: There was equivalent cell kill with all three types of asparaginase. The mean in vitro TCKs for E. coli. Erwinia. and pegaspargase were 31%. 39%. and 36%. respectively (P = 0.63). The mean LCKs in marrow of patients exposed to E. coli. Erwinia. and pegaspargase were 69%. 74% and 65%. respectively (P = 0.88). The lack of response to asparaginase in vitro predicted a higher risk for clinical relapse regardless of risk assignment (12 leukemic events among 21 in vitro nonresponders: 57%. P < 0.001). There was no difference in acute toxicity among the three asparaginase preparations.Conclusions: All three asparaginase preparations produced equivalent LCKs in in vitro and in vivo analyses. In vitro response to asparaginase provided a risk group-independent prognostic factor.

ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Purpose: The clinical value of metaiodobenzylguanidine (mIBG) scintigraphy in patients with disseminated neuroblastoma (NB) at the time of diagnosis and after induction chemotherapy was evaluated.Patients and Methods: The medical records and imaging studies of 30 patients with stage 4 NB who underwent mIBG scintigraphy and99mTc hydroxy methylene diphosphonate bone scintigraphy at the time of diagnosis were reviewed. Scores were calculated for the mIBG and bone scintigrams, and outcome according to the initial and follow-up imaging studies was determined.Results: Discrepancies between bone scintigraphy and mIBG osteomedullary localization were seen in six patients. For the entire cohort. 2–year event-free survival did not significantly differ for the group of patients with initial mIBG or bone scintig-raphy scores ⩾ 10 compared to those with scores < 10 (P = 0.23 and 0.61. respectively). However, for patients older than 1 year, a trend associating worse outcome with mIBG scores ⩾ 10 at diagnosis was seen (P = 0.08). A trend correlating abnormal mIBG scintigraphy after induction therapy and poor outcome was also observed (P = 0.09). Outcome did not correlate with the results of the bone scintigram studies performed after induction chemotherapy (P = 0.68).Conclusion: Because a discordance between mIBG and bone scintigraphy results were seen in a subset of stage 4 NB patients, both imaging studies should be performed at the time of diagnosis. mIBG imaging studies performed at the time of diagnosis and after induction chemotherapy may be of prognostic value, particularly in stage 4 patients older than 1 year.

ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Purpose: Apoptosis plays a crucial role in normal development and mediates tumor response to chemotherapy. This study investigated the pattern of apoptotic gene expression in brain tumor tissue specimens and cell lines.Materials and Methods: BCL2, BCLXL, BCLXS, and BAX transcripts were amplified using reverse transcriptase polymerase chain reaction in 7 high-grade gliomas (HGGs), 7 ependymomas, and 6 cell lines (2 glioblastomas, 3 medulloblastomas, and 1 supratentorial-primitive neuroectodermal tumor [PNET]). Immunohistochemical staining for BCL2. BCLX, BAX, and p53 was performed in 7 pediatric low-grade gliomas (LGGs) and 7 pediatric HGGs.Results: Six of seven gliomas, all ependymomas, and all glioblastoma and medulloblastoma cell lines expressed BCLXLand BAX. BCL2 expression was only detected in the supratentorial PNET line PFSK. BCLXSwas absent in all tumors. By immunohisto-chemistry, no glial tumors stained positively for BCL2. Similar BAX and BCLX protein expression was observed in LGG and HGG. Three of five glioblastomas showed significant p53 expression.Conclusions: Coexpression of proapoptotic and antiapoptotic genes in human brain tumors supports the hypothesis that the relative expression of competing genes determines apoptotic threshold.

ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Purpose: Idarubicin (4–demethoxy-daunorubiein) is more potent and less cardiotoxic than the commonly used anthracyclines. doxorubicin and daunorubicin. In addition, idarubicin is metabolized to an active metabolite, idarubicinol, in contrast to other anthracyclines whose alcohol metabolites are much less active than the parent drug. The current study was performed in nonhuman primates to determine the plasma and cerebrospinal fluid (CSF) pharmacokinetics of idarubicin and idarubicinol and to compare them to the pharmacokinetics of daunorubicin and daunorubicinol.Methods: A dose of 30 mg/m2of daunorubicin or 8 mg/m2of idarubicin was administered intravenously over 15 minutes. Plasma and CSF were sampled frequently from the end of the infusion to 72 to 96 hours after infusion. Drug and metabolite concentrations were measured using high-pressure liquid chromatography (HPLC).Results: Daunorubicin elimination from plasma was triphasic with a terminal half-life of 5.9 + 1.8 hours, area under the concentration-time curve (AUC) 22.5 + 9.2 μmol/L min. and clearance 2790 + 960 mL/min/m2. Daunorubicinol elimination was biphasic with a terminal half-life 10.2 + 2.3 hours and an AUC 74.5 + 5.3 μmol/L min. Idarubicin elimination was triphasic with terminal half-life of 12.3 + 11.4 hours, a AUC 10.8 + 3.7 μmol/L min, and clearance 1650 +610 mL/min/m2. Idarubicinol elimination was biphasic with a terminal half-life 28.7 + 4.2 hours and AUC 67 + 9.8 μmol/L min. CSF penetration was low for both parent drugs and their metabolites. CSF idarubicin was measurable at a single time point (1 hour after administration) for 2 animals, and was not measurable for the third. The CSF to plasma concentration ratio at that time point was 8% in 1 animal and 15% in the other. Idarubicinol was detected in 2 to 4 samples at various times, appearing as early as 1 hour in 1 animal and persisting as late as 48 hours in another. The CSF to plasma concentration ratio at corresponding time points was 1.9 + 0.6%. Daunorubicin was measurable for < 6 hours after intravenous administration. For individual animals, the mean CSF to plasma concentration ranged from 4% to 12%. Daunorubicinol was detectable by 1 hour in 2 of 3 animals and by 3 hours in the other, and remained detectable at 24 hours in 2 of 3. The terminal half-life of daunorubicinol in CSF was 8.8 + 1.3 hours, the AUC was 1.8 + 1.5 μmol/L min. and the AUCCSFto AUCplasmaratio was 2.4 + 1.9%.Conclusion: Idarubicin, idarubicinol. daunorubicin, and daunorubicinol penetrate poorly into the CSF after intravenous administration.

ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Purpose: The phenotype of the proliferating cells in two patients with erythrophagocytic histiocytosis is described. These 6– and 18–month-old female patients presented with fever, anemia, hepatosplenomegaly, and lymphadenopathy.Materials and Methods: Clinical histories were reviewed, and pathological specimens of both patients were studied by histology, and electron microscopy/immunohistochemistry using antibodies against macrophage and Langerhans cell (LC) antigens. Results: Histology revealed prominent erythrophagocytosis of proliferating histiocytes. By immunohistochemistry, conventional macrophage (HAM-56, αl-antitrypsin, αl-antichymotrypsin, lisozyme, CD68, and α-subunit of S-100 protein) and LC (CD1a and S-100 protein) markers were positive, as well as double labeling for CD1a and αl-antichymotrypsin, in a majority of proliferating cells. Ultrastructural examination revealed Birbeck granules and prominent phagolysosomes frequently in the same cell.Conclusions: The hybrid ultrastructural and immunohisto-chemical phenotype between phagocytic macrophage and LC of proliferating histiocytes supports the common origin of these different histiocyte subtypes. This unusual phenotype might be the expression of the proliferating (hybrid) precursor or be the effect of unknown stimuli. Additional cases of childhood erythrophagocytic histiocytosis should be studied with immunophe-notyping and ultrastructure to determine whether the hybrid phenotype represents a specific entity or an epiphenomenon.

ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Purpose: Subcutaneous panniculitic T-cell lymphoma is reported in a child with idiopathic myelofibrosis. Both disease entities are rarely seen in children.Patient and Methods: A girl aged 5 years and 9 months had pancytopenia and severe constitutional symptoms. Idiopathic myelofibrosis was subsequently diagnosed.Results: A transient response was achieved after treatment with a course of high-dose methylprednisolone therapy. However, proptosis and skin nodules developed during tapering of steroid therapy. A computed tomography scan of the orbit also revealed a mass lesion in the right lacrimal gland region. A skin biopsy specimen showed a subcutaneous panniculitic T-cell lymphoma. The clinical course was marked by high fever, profound pancytopenia, massive gastrointestinal bleeding, and severe, recurrent infections. Her condition rapidly deteriorated, and she died from polymicrobial sepsis 4 months after her initial examination.Conclusions: Subcutaneous panniculitic T-cell lymphoma is a distinctive clinicopathologic entity that is rarely seen in children. The association of myelofibrosis and peripheral T-cell lymphoma as seen in this patient has been rarely reported.

ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Purpose: Central nervous system (CNS)-Tcell lymphoproliferative disorder (T-LPD) developing during the course of chronic active Epstein-Barr virus (CAEBV) infection is reported.Patients and Methods: CAEBV was diagnosed in a 14–month-old boy with fever, cytopenia. hepatosplenomegaly. and abnormal high titers of anti-Epstein-Barr virus (EBV) antibodies. At 8 years of age. he had a splenectomy because of progressive disease.Results: After 27 months of clinical remission, muscle weakness and paresthesia developed. Magnetic resonance imaging of his brain showed spotty T2 prolongation in left parietal, bilateral frontal, and temporal white matter with meningeal enhancement. Brain biopsy revealed the cerebral infiltration of CD3+, CD4+, CD8--, CD45RO+, CD56--, and EBV-encoded RNA 1+cells.Conclusions: The CNS involvement of EBV-associated T-LPD is a rare but serious complication in CAEBV without known underlying immunodeficiency.

ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Purpose: Gaucher disease should be considered in the differential diagnosis of a patient with Epstein-Barr virus (EBV) infection who has unexplained or disproportionate splenomegaly.Patients and Methods: A previously asymptomatic adolescent with EBV-associated infectious mononucleosis and massive splenomegaly is described. He was found to have Gaucher disease on bone marrow biopsy, which was performed to exclude a hematologic malignancy. The diagnosis was confirmed by assay of β-glucosidase enzyme activity.Results: Regression of splenomegaly and improving hematologic indices.Conclusion: Patients with infectious mononucleosis and disproportionate organomegaly should be investigated to exclude a hematologic malignancy or an underlying storage disorder such as Gaucher disease.

ISSN:1077-4114    

出版商:OVID    

年代:1999

数据来源: OVID