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C A Mullen,
D Petropoulos,
W M Roberts,
M Rytting, T Zipf,
K W Chan,
S J Culbert,
M Danielson,
S S Jeha,
J F Kuttesch,
K V Rolston
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ABSTRACT: Fever and neutropenia (F&N) is a common complication of cancer chemotherapy. It is conveniently managed by hospitalization and empiric administration of parenteral antibiotics. This study attempted to determine whether pediatric cancer patients with F&N identified as low risk for morbidity and mortality by clinical criteria at the time of presentation could be treated safely as outpatients.
Seventy-three episodes of F&N in 41 patients were studied prospectively over 2 years. Eligibility criteria included age > or =2 years, reliable caretakers, and residence within 1 hour of the hospital. Exclusion criteria included hemodynamic instability, dehydration, severe mucositis, pneumonia, leukemia/lymphoma induction therapy, bone marrow transplantation, or other serious comorbidity. Patients were evaluated, received a single dose of intravenous ceftazidime, and were observed for 3-16 hours. They were randomized to receive either oral ciprofloxacin or intravenous ceftazidime as outpatients. Patients were seen daily until they had been afebrile for at least 48 hours and had a rising absolute phagocyte count of >500 cells/microL.
Sixty-three of 73 episodes (86%) were successfully managed on an outpatient basis. For 31 of 33 episodes in the ceftazidime arm, the patients remained outpatients, compared with 32 of 40 in the ciprofloxacin arm; this difference was not statistically significant. On average, patients remained febrile for 2.7 days and were treated for 4.7 days. Seventy-seven percent of episodes required no modification of initial antibiotic therapy. Of the 10 patients who were hospitalized, 4 had prolonged fever and 3 had emesis. Protracted neutropenia was associated with the need for hospitalization. There were no deaths, intensive care unit transfers, or serious complications.
Carefully selected low risk children with fever and neutropenia can be treated safely as outpatients. Close daily medical scrutiny is required.
Cancer 07/1999; 86(1):126-34. · 4.77 Impact Factor
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C A Mullen,
D Petropoulos,
W M Roberts,
M Rytting, T Zipf,
K W Chan,
S J Culbert,
M Danielson,
S S Jeha,
J F Kuttesch,
K V Rolston
[show abstract]
[hide abstract]
ABSTRACT: To measure resource allocation in outpatient management of fever and neutropenia in low-risk pediatric patients with cancer and its impact on their families.
A prospective clinical trial was conducted. Eligible patients received a single dose of intravenous (IV) antibiotics and were observed for several hours in clinic. Patients were randomly assigned to continue either IV or oral antibiotics and were seen daily as outpatients. Charges were calculated based on the number of resources used and Medicare/Medicaid reimbursement schedules. A questionnaire was used to measure the impact of outpatient treatment on the family.
Seventy-three episodes of fever and neutropenia were studied. The median duration of treatment was 4 days. Eighty-six percent of the episodes were managed without hospitalization. The median calculated charge was $1840. The median calculated charge for patients receiving oral antibiotics was $1544 and was significantly less than the $2039 median charge for outpatients treated with IV antibiotics. The estimated charge for comparable inpatient treatment was $4503. Nearly all families preferred outpatient care, and few reported a loss of work hours or increased child care expenses.
Outpatient treatment of low-risk episodes of fever and neutropenia is substantially less costly than inpatient care and is preferred by most families.
Journal of Pediatric Hematology/Oncology 04/1999; 21(3):212-8. · 1.16 Impact Factor
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ABSTRACT: High-dose, continuous infusion of intravenous mercaptopurine (HD 6MP) followed by intermediate-dose continuous cytarabine (ID Ara-C) has been shown to produce remissions in children with relapsed acute myeloid leukemia (AML). The purpose of this pilot study was to explore the feasibility of using this drug regimen as a component of treatment during the first remission of AML. Of 17 children with newly diagnosed AML registered in the study, 14 developed complete remission on conventional induction therapy and subsequently received the HD 6MP and ID Ara-C combination. The dosages of HD 6MP were escalated from 500 mg/m2 to 1250 mg/m2 in 24-hr infusions. The initial dosages of ID Ara-C were escalated from 250 mg/m2 to 650 mg/m2/24 hr and from 1 day to 4 days. Conventional treatment for AML was administered simultaneously. Seven of the 14 children remain in initial complete remission for 15 to 46 months and have completed treatment. Severe pancytopenia was observed in all patients, but there were no toxic deaths and no deaths during remission. The inclusion of HD 6MP and ID Ara-C in the treatment of AML in first remission appears to be feasible. Evaluation of its efficacy will require a comparative clinical trial.
Cancer Investigation 02/1997; 15(2):121-6. · 1.85 Impact Factor
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ABSTRACT: This phase I/II study was designed to explore the feasibility, toxicity, and potential efficacy of administering high-dose continuous intravenous mercaptopurine (6MP) followed by intermediate-dose continuous intravenous cytarabine (Ara-C) to children with relapsed or unresponsive acute leukemia.
Twenty-three children with relapsed or unresponsive acute leukemia (13 myeloid, 10 lymphoid) were entered onto the study. After initial hydration and alkalinization, 1,000 or 1,250 mg/m2 of 6MP was administered by continuous intravenous infusion over 24 hours. Following another period of hydration, 500 mg/m2 of Ara-C was administered by continuous intravenous infusion daily for 4 days. In 17 children, plasma concentrations of 6MP were measured at hours 4, 24, and 27 of the 6MP infusions. Plasma concentrations of Ara-C were measured at hours 8, 24, 48, 72, and 96 of the Ara-C infusions. Intracellular Ara-C triphosphate (Ara-CTP) concentrations were measured in peripheral-blood leukemia cells of the five patients with sufficient cells for measurement. Children who developed remission received repeated courses of this regimen every 3 to 4 weeks until relapse or completion of 12 courses.
Of 13 children with acute myeloid leukemia (AML), six developed complete remissions (CRs) lasting 7 months to nearly 4 years. Two children remain in CR with normal growth, development, and health 3 years after cessation of treatment. Of 10 children with acute lymphoid leukemia (ALL), one had a CR of 2 months' duration. Dose-limiting toxicity consisted of severe hematosuppression with fever, neutropenia, and serious infection. There were two toxic deaths. The mean steady-state plasma concentrations of 6MP were approximately 4 mumol/L and of Ara-C approximately 3 mumol/L. The median Ara-CTP concentration in peripheral-blood leukemia cells was 308 mumol/L at hour 8 of the Ara-C infusion.
High-dose continuous intravenous 6MP followed by intermediate-dose intravenous Ara-C produced CRs of longer than 6 months in approximately half of children with relapsed or unresponsive AML. Further study of this drug regimen is justified.
Journal of Clinical Oncology 04/1994; 12(3):587-95. · 18.37 Impact Factor
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ABSTRACT: The Philadelphia (Ph1) chromosome is present in greater than 90% of patients with chronic myelogenous leukemia (CML) and in 2% to 20% of those with acute leukemias, for which it is an important prognostic marker too. The chimeric BCR-ABL mRNAs resulting from the translocation encode either a 210-Kd or a 190-Kd protein. The techniques used to detect Ph1 chromosome include karyotyping, Southern analysis to demonstrate bcr rearrangement, and polymerase chain reaction to amplify the BCR-ABL transcripts. However, the routine performance of these methods by clinical laboratories is cumbersome, time consuming, and exposes laboratory personnel to radioisotopes. We describe here the clinical application of a new method, the hybridization protection assay (HPA), which uses chemiluminescent acridinium-ester-labeled probes in conjunction with PCR for detection of the amplified BCR-ABL sequences. The method is sensitive, specific, and can reliably distinguish between the transcripts for P190BCR-ABL and P210BCR-ABL. In contrast to the 2 days or longer required for conventional hybridization, HPA analysis can be completed in less than 30 minutes. We have successfully used this method to analyze 60 leukemia samples (34 from Ph1-negative acute leukemias; 6 from Ph1-positive acute leukemias; and 20 from CML) with complete correlation (of BCR-ABL positivity or negativity) with the results of karyotype or Southern Blot analysis of genomic DNA for bcr rearrangement. Therefore, the HPA, in conjunction with PCR, appears to provide a rapid and reliable test for the diagnosis of Ph1-positivity.
Blood 02/1991; 77(2):238-42. · 9.90 Impact Factor
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Journal of Pediatric Hematology/Oncology 20(5):516-7. · 1.16 Impact Factor
