ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID

ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

PurposeThis pilot study focussed on whether sequential molecular detection of minimal residual disease (MRD) in bone marrow (BM) could predict the outcome of patients with advanced neuroblastoma.Patients and MethodsBone marrow samples from 21 patients older than age 12 months with stage IV neuroblastoma were sequentially examined for tumor cell contamination by detecting tyrosine hydroxylase (TH) messenger ribonucleic acid (mRNA) using reverse transcription-polymerase chain reaction (RT-PCR). Twenty patients received myeloablative therapy with hematopoietic stem cell transplantation after achieving complete remission.ResultsAll BM samples of patients except that of one patient was cytologically positive for neuroblastoma cells at diagnosis, and they became negative for neuroblastoma cells within 3 months by cytologic examination. By RT-PCR analysis, BM samples of all patients were positive for TH mRNA at diagnosis, and samples of 19 patients became negative for TH mRNA 1 to 13 months after the start of chemotherapy. Six patients whose BM samples became negative for TH mRNA within 4 months after the start of chemotherapy remained alive without evidence of disease (median 76 mos, range 36–91). In contrast, out of 15 patients whose BM samples remained positive, 10 patients had relapse develop and 9 patients died from disease (median 15 mos, range 10–25). There was a statistically significant difference in disease-free survival between the two groups (P< 0.05).ConclusionPersistence of MRD in BM may predict poor prognosis in advanced neuroblastoma.

ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

PurposeTo determine whether the morphologic features of posttransplant lymphoproliferative disease (PTLD) correlated to a response to therapy.Patients and MethodsWe reviewed our experience with PTLD in the pediatric population. We identified 32 patients with a total of 36 episodes of PTLD. The diagnosis was confirmed by tissue examination and classified according to the degree of monomorphic features of the lesion. Thirty-four of 36 episodes were managed with immunosuppression reduction, and the patients were assessed for their response to this strategy. Chemotherapy was used to treat 10 of 15 patients who had progressive disease, and their subsequent course was also analyzed.ResultsSixteen of 17 (94%) patients with polymorphic morphology responded to immunosuppression reduction compared with only 5 of 17 (29%) patients with monomorphic features (P< 0.001). All of the patients with progressive disease who did not receive additional therapy died. Standard chemotherapy regimens for lymphoma were administered to 10 patients with progressive disease, with a high response rate (90%), durable remissions, and acceptable toxicity.ConclusionsWe conclude that the morphologic characteristics of PTLD provide information to potentially help guide treatment strategies in the management of this disease. Standard chemotherapy regimens for malignant lymphoma appear to be a viable treatment option for patients with progressive disease, although further investigation is needed.

ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

PurposeAn evaluation of colony-stimulating factor (CSF) use in pediatric stem cell transplantation (SCT) was conducted to identify potential cost-efficiencies while preserving institutional standards of patient care.MethodsClinical and pharmacy records of the 55 SCTs performed during fiscal year 1995 were reviewed. Material costs per vial and per microgram, exclusive of preparation or overhead costs, were used. The best costing strategy was defined as the least expensive stocking and dispensing practice to deliver the drug actually used during the study period.ResultsCSFs were used in 35 of 55 transplants; 68% of usage was protocol-mandated to enhance engraftment; the remainder was associated with life-threatening complications of SCT. All use was consistent with published evidence-based guidelines. Changes in stocking and dispensing practices would result in an overall annual savings of $48,162 (fiscal year 1995 dollars), a 39% decrease in cost without a change in clinical application.ConclusionsOur analysis demonstrates that stocking and dispensing practices place significant fiscal burden in the care of pediatric-aged patients and must be carefully considered. This analysis presents a model for evaluating all components of drug cost from a global perspective, highlighting a need for examination of pharmacy and manufacturing as well as clinical practices.

ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

PurposeTo assess if the abundance of apoptotic tumor cells is an independent prognostic factor in primitive neuroectodermal tumors (PNET) of the central nervous system.Patients and MethodsFormalin-fixed paraffin-embedded tumor tissue sections from 78 clinically well-characterized children with PNET were evaluated by terminal deoxytransferase-mediated deoxyuridine-5´-triphosphate (dUTP) nick-end labeling (TUNEL). Apoptotic indices (AI) were determined by counting TUNEL-positive tumor cells either in the highest staining region (AI hot spot) or in at least 15 randomly chosen fields (AI random). The AI hot spot and AI random were then correlated with clinical variables and survival outcome.ResultsAI hot spot (median 0.56%; range 0%–6.54%) and AI random (median 0.30%; range 0%–3.21%) showed considerable intertumor variability. Moreover, 53% of the evaluated PNET showed a more than two-fold difference between AI hot spot and AI random, showing important intratumoral variability of the abundance of apoptotic cells in a subset of the evaluated PNET. No significant associations were found between AI hot spot and AI random with clinical variables or survival outcome.ConclusionThe apoptotic index does not predict survival outcome and is not specifically associated with clinical variables of prognostic significance in childhood PNET.

ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

PurposeThe objectives of this study were: 1) to compare the time to hematologic recovery (absolute neutrophil count [ANC] ≥1,000/mm3and platelet count ≥100,000/mm3) in a randomized prospective study of two doses of granulocyte colony-stimulating factor (G-CSF) (5.0 vs. 10.0 &mgr;g/kg per day) after ifosfamide, carboplatin, and etoposide (ICE) chemotherapy; and 2) to determine the response rate (complete response [CR] + partial response [PR]) of ICE in children with refractory or recurrent solid tumors.Patients and MethodsFrom June 1992 until November 1994, 123 patients with recurrent or refractory pediatric solid tumors were treated with ifosfamide (1,800 mg/m2per day x 5), carboplatin (400 mg/m2per day x 2), and etoposide (100 mg/m2per day x 5) and randomized to receive either 5.0 &mgr;g/kg per day or 10.0 &mgr;g/kg per day of G-CSF subcutaneously until recovery of ANC to ≥1,000/mm3.ResultsThe incidence of grade 4 neutropenia during the first course was 88%. Median time from the start of chemotherapy to ANC ≥1,000/mm3for all patients during courses 1 and 2 was 21 and 19 days, respectively. The incidence of developing platelet count ≤20,000/mm3during course 1 was 82%. The median time from the start of the course of chemotherapy to platelet recovery ≥100,000/mm3for all patients during courses 1 and 2 was 27 days. There was no significant difference in the median time of ANC recovery, platelet recovery, or incidence of grade 4 neutropenia; and in the median days of fever and the incidence of infections requiring hospitalization and intravenous antibiotics during courses 1 and 2, there was no significant difference between the two doses of G-CSF. One hundred eighteen patients were evaluated for response to ICE. The overall response rate (CR + PR) in this study was 51% (90% confidence interval, 43%–59%). The CR rate for all diagnostic categories was 27%. The Kaplan-Meier estimates of 1-year and 2-year survival probabilities for all patients were 52% and 30%, respectively.ConclusionIn summary, this combination of chemotherapy (ICE) was associated with a high CR rate (27%) in children with recurrent or refractory solid tumors, but also with a high incidence of grade 4 neutropenia and thrombocytopenia. Doubling the dose of G-CSF from 5.0 to 10.0 &mgr;g/kg per day after ICE chemotherapy did not result in an enhancement of neutrophil or platelet recovery or the incidence of grade 4 neutropenia developing.

ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

PurposeDiamond–Blackfan anemia (DBA) is a congenital pure red cell aplasia, usually presenting in infancy or early childhood. A review of the literature strongly supports a predisposition to hematopoietic malignancy. Recently, solid tumors have been reported, some attributable to hemosiderosis and/or androgen therapy. Two cases of osteogenic sarcoma have also been documented. An analysis from the Diamond–Blackfan Anemia Registry was performed to evaluate the cancer risk in patients with DBA.MethodsThe Diamond–Blackfan Anemia Registry of North America (DBAR) is a comprehensive database of patients with DBA enrolled, after informed consent, through outreach to pediatric hematologists and family groups. The patients and/or their families complete a detailed questionnaire, and a review of medical records and telephone interviews are performed to complete and clarify the information provided.ResultsOf the 354 patients registered in the DBAR, there were six patients meeting the accepted diagnostic criteria for DBA who were found to have malignancies. Three patients had osteogenic sarcoma diagnosed, one with myelodysplastic syndrome, one with colon carcinoma, and one with a soft tissue sarcoma.ConclusionThere appears to be an association of osteogenic sarcoma with DBA. A young age at presentation may be a feature of DBA-associated osteogenic sarcoma. Because of the immaturity of the database, the actuarial risk for osteogenic sarcoma and other cancers in individuals with DBA cannot be ascertained. Speculation is made regarding the nature of the molecular defect leading to the association of DBA and osteogenic sarcoma.

ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

Chemotherapy for malignant neoplasms sometimes causes unconjugated hyperbilirubinemia in the absence of liver dysfunction. We analyzed the association of chemotherapy-induced hyperbilirubinemia with mutations of the bilirubin uridine-5´-diphosphate (UDP)-glucuronosyltransferase gene(UGT1A1)from two leukemic patients in whom chemotherapy resulted in a hyperbilirubinemic response. We isolated genomic DNA from peripheral blood samples and amplifiedUGT1A1by polymerase chain reaction. The amplified DNA fragments were analyzed by direct sequencing. The genes of the two patients revealed an identical heterozygous missense mutation in exon 1 (211G→A: G71R). ThisUGT1A1mutation may be the basis of chemotherapy-induced unconjugated hyperbilirubinemia.

ISSN:1077-4114    

出版商:OVID    

年代:2001

数据来源: OVID