Practice guidelines for lipid-based amphotericin B in stem cell transplant recipients.

OBJECTIVE: To provide clinicians who practice in the stem cell transplantation (SCT) setting with practical guidelines for the use of lipid-based amphotericin B (AmB) formulations in SCT patients who have documented or probable invasive fungal infections, are experiencing neutropenic fever, or require secondary prophylaxis for fungal infections. DATA SOURCES: Recommendations are based on the results of a two-day consensus meeting that convened clinicians versed in the management of infectious complications in patients undergoing SCT. This meeting, which was held October 21-23, 1998, in Orlando, Florida, was sponsored by an educational grant from The Liposome Company. In addition, primary articles were identified by MEDLINE search (1980-December 1999) and through secondary sources. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified from the data sources were evaluated, and all information deemed relevant was included in this review. DATA SYNTHESIS: Immunocompromised patients, particularly patients undergoing high-dose chemotherapy with SCT, experience a high degree of morbidity and mortality from invasive fungal infections. Historically, treatment for such infections with conventional AmB had been limited primarily by its associated nephrotoxicity. Lipid-based formulations of AmB have helped to advance the management of invasive fungal infections in the SCT population by offering a treatment alternative that allows for administration of adequate amounts of active drug to produce clinical and mycologic responses, compared with conventional AmB, in a delivery system that is less nephrotoxic. Unfortunately, these agents are relatively expensive. Therefore, patients who are candidates for lipid-based products must be selected carefully. CONCLUSIONS: Practical guidelines are provided for the use of lipid-based AmB formulations in SCT patients who have documented or probable invasive fungal infections, are experiencing neutropenic fever, or require secondary prophylaxis for fungal infections.

Antifungal effects of yeast-derived rhu-GM-CSF in patients receiving high-dose chemotherapy given with or without autologous stem cell transplantation: a retrospective analysis.

Systemic fungal infections (SFI) in patients receiving high-dose chemotherapy (HDC) are a frequent cause of morbidity and mortality. Preclinical studies have reported augmented antifungal activity of monocytes, macrophage cells, and neutrophils exposed to certain colony-stimulating factors (CSF), including GM-CSF. We conducted a retrospective descriptive epidemiologic study to examine the characteristics of 145 consecutive patients receiving HDC administered with or without autologous stem cell transplantation (ASCT) and who subsequently received either GM-CSF and G-CSF, G-CSF alone, GM-CSF +/- IL-3 or no CSF. The analysis of this patient population sought to define the incidence of SFI and its relationship to therapy with monocyte/macrophage-stimulating (MMS group) cytokines (GM-CSF and G-CSF; GM-CSF +/- IL-3) or to cytokines which do not result in monocyte/macrophage stimulation (NMMS group, G-CSF alone or no CSF). Risk factors for the development of SFI were balanced between the MMS (n = 70) and NMMS (n = 75) groups. Two patients (2.9%) in the MMS and nine patients (12%) in the NMMS groups developed SFI. The risk ratio for developing SFI in the NMMS group compared to the MMS group was 4.20 (P = 0.023). This relationship was confounded, however, by the diagnosis of hematologic tumor or solid tumor (RR = 3.15, P = 0.082). SFI was the primary cause or major contributing factor in five of the 10 total deaths in our study population. Four SFI-related deaths occurred in the NMMS group and one SFI-related death occurred in the MMS group. Our data suggest a protective role for GM-CSF, IL-3 or other MMS cytokines in preventing SFI in patients receiving HDC. This should be further investigated as a potential complementary approach to conventional strategies in antifungal prophylaxis for patients receiving HDC.

Pegaspargase versus asparaginase in adult ALL: a pharmacoeconomic assessment.

Asparaginase is an effective treatment for patients with acute lymphocytic leukemia (ALL). Unfortunately, asparaginase therapy is associated with a high incidence of hypersensitivity reactions (up to 73%), including life-threatening anaphylaxis, and its half-life of approximately 20 hours necessitates daily administration. Pegaspargase, a modification of L-asparaginase, has a longer half-life (357 hours), a decreased incidence of hypersensitivity reactions, and when doses every 14 days, provides comparable efficacy to asparaginase; however, it is much more expensive per single-dose vial ($980.00 vs $52.38). To determine the pharmacoeconomic impact of the two agents, we conducted a cost-minimization analysis for three common adult ALL protocols. Results showed that pegaspargase was significantly less costly to payers on an inpatient or outpatient basis and warranted addition to our formulary.

Technical considerations in the preparation and dispensing of chemotherapy.

The safe handling of cytotoxic agents is intimately related to the technical aspects of drug preparation, dispensing, and administration. The appropriate equipment, supplies, protective clothing, and waste disposal systems must be available to the health care worker who is called upon to prepare cytotoxic agents. In addition, the health care worker must be adequately trained in and familiar with the safe use of these products and equipment and the preparation techniques or manipulations necessary during cytotoxic drug compounding. The article describes in detail and reviews the technical considerations, such as aseptic technique, proper use of the biological safety cabinet, gowning and gloving, labeling, and waste disposal, that are essential to the safe preparation and dispensing of chemotherapy.

Certification program in antineoplastic drug preparation for pharmacy technicians and pharmacists.

A formal training program for technicians who prepare cytotoxic agents and pharmacists who check the doses is described. To handle an overwhelming workload in an oncology satellite pharmacy and to enable the pharmacists there to increase their clinical involvement, a program was developed to train technicians to prepare antineoplastic doses and pharmacists to check the technicians' work. The program consists of two days of classroom instruction, three weeks of hands-on training, and a written examination. In addition to handling and preparation of antineoplastic drugs, other topics related to oncology are covered to give the participants a better understanding of cancer and its treatment. The technicians must complete a refresher program annually. From 1991 to 1993, 15 pharmacists and 14 technicians and pharmacy students completed the program. The technicians have taken on additional responsibilities in the satellite pharmacy, including managing the inventory of oncology drugs. Implementation of a comprehensive cancer chemotherapy training class for technicians and pharmacists has benefited the pharmacy in terms of labor and inventory control.

An overview of chemotherapy toxicities.

Understanding the toxicities associated with cancer chemotherapeutic agents is essential to pharmacists involved in the clinical management of oncology patients. Anticipation of various treatment-related toxicities may provide the opportunity for pharmacists to develop intervention strategies that could minimize or eliminate an expected side effect of chemotherapy such as myelosuppression, nausea, or emesis. Effective management of chemotherapy toxicities may lead to decreased lengths of stay in the hospital or administration of chemotherapy in the outpatient setting. This article addresses the onset of chemotherapy toxicities, the major organ system toxicities, and the management of many of these chemotherapy-induced toxicities. Chemotherapy dose modifications are discussed as well as maximum lifetime doses and the use of prophylactic medications to prevent various side effects.

Make costly physicians accountable.

Physicians make the majority of decisions about the type and quantity of medical care, but cost-sharing mechanisms intended to control costs place the burden upon the patient. This article proposes a variety of mechanisms for placing this burden upon the small group of physicians identified as being excessively costly.