Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Jan 2001
Randomized Controlled Trial Comparative Study Clinical TrialDouble-blind comparative trial of oral ondansetron versus oral granisetron versus IV ondansetron in the prevention of nausea and vomiting associated with highly emetogenic preparative regimens prior to stem cell transplantation.
The optimal management of transplantation preparative regimen-induced nausea and vomiting remains unknown. We conducted a Phase III double-blind study to determine the efficacy and costs of oral ondansetron versus oral granisetron versus IV ondansetron and PRN rescue antiemetics for the prevention/control of nausea and vomiting associated with high-dose chemotherapy or chemoradiotherapy prior to stem cell transplantation. One hundred two patients were randomized to receive either 8 mg PO ondansetron every 8 hours, 1 mg PO granisetron every 12 hours, or 32 mg IV ondansetron every 24 hours plus 10 mg IV dexamethasone daily during and 1 day after the various preparative regimens. ⋯ None of the differences were statistically significant. A cost analysis revealed significant differences among all arms (P = .0001, all comparisons). All 3 regimens had similar efficacy in this BMT population; oral ondansetron was the most cost-effective.
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Biol. Blood Marrow Transplant. · Jan 2001
ReviewMethodologic guidelines for the design of high-dose chemotherapy regimens.
The objective of this report is to review the research methods that have been used in the design, analysis, and reporting of Phase I dose-escalation studies of high-dose chemotherapy (HDCT) with bone marrow or stem cell support and to propose new guidelines for such studies that incorporate emerging principles of pharmacology, toxicity assessment, statistical design, and long-term follow-up. ⋯ Phase I clinical trials in the HDCT setting have been designed, analyzed, and reported using heterogeneous methods that limited their application to Phase II and II investigations. Moreover, correlative pharmacologic analyses have not been routinely undertaken during this critical Phase I stage. We propose guidelines for the design of new Phase I studies of HDCT based on 4 essential elements: (1) rational preclinical and clinical pharmacologic foundation for the regimen and for the agent selected for dose escalation; (2) incorporation of analytical pharmacology in the design and analysis of the regimen under investigation; (3) clear, prospective definitions of the dose- or exposure-limiting toxicities that can be distinguished from modality-dependent toxicities; selection of an appropriate toxicity grading scale, including an assessment of cumulative, delayed, and long-term effects of HDCT, particularly when designing tandem or repetitive cycle regimens; and (4) statistical input into the design, execution, analysis, interpretation, and reporting of these studies.
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Biol. Blood Marrow Transplant. · Jan 2001
Comparative StudyCD31 mismatching affects marrow transplantation outcome.
Graft-versus-host disease (GVHD) complicating allogeneic bone marrow transplantation (BMT) is often attributed to mismatched minor histocompatibility antigens (mHags), which are poorly defined in humans. CD31 is a candidate human mHag relevant to acute GVHD, but reports disagree about its level of significance, the role of HLA restriction, and the relative importance of different polymorphic codons within the molecule. We therefore examined in greater detail the impact of CD31-matching on BMT outcome in a prospective study from a single institution. ⋯ CD31 nonidentity showed a trend but failed to achieve statistical significance as a risk factor for relapse and for chronic GVHD. In conclusion, donor-recipient CD31 nonidentity is a significant risk factor for survival and for severe acute GVHD in HLA-identical sibling BMT. The stronger associations with codon 563/670 suggest that polymorphism may be more important than the linked polymorphism at codon 125.
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Biol. Blood Marrow Transplant. · Jan 2001
Randomized Controlled Trial Clinical TrialRandomized open-label trial of dolasetron for the control of nausea and vomiting associated with high-dose chemotherapy with hematopoietic stem cell transplantation.
A prospective open-label trial was performed to compare the efficacy of dolasetron with that of ondansetron or granisetron (standard therapy) for prevention of nausea and vomiting associated with high-dose chemotherapy with or without total body irradiation followed by hematopoietic stem cell transplantation (HSCT). In a university teaching hospital setting, 62 patients were randomized to receive either dolasetron 100 mg daily or standard doses of ondansetron or granisetron. In addition to objective data such as number of episodes of emesis and quantity of rescue antiemetics required, 100 mm visual analogue scales were used to rate nausea, appetite, and changes in taste. ⋯ Patients in the standard therapy group used fewer rescue antiemetics and also rated more favorably on selected questions of the visual analogue scale. No differences in safety parameters or adverse effects were reported. At doses prescribed in this study, dolasetron was less effective than granisetron or ondansetron in preventing nausea and vomiting associated with high-dose chemotherapy/total body irradiation followed by HSCT.
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Biol. Blood Marrow Transplant. · Jan 2001
ReviewDiagnosis and epidemiology of community-acquired respiratory virus infections in the immunocompromised host.
Infections due to community-acquired respiratory viruses are important causes of morbidity and mortality among immunocompromised patients. Respiratory syncytial virus, influenza viruses, and parainfluenza viruses are the most frequent causes of serious lower respiratory tract infections in this patient population. Early diagnosis, often possible with the use of rapid detection assays, is essential for optimal management and prevention of the spread of these serious infections to other vulnerable patients.