First-cycle absolute neutrophil count can be used to improve chemotherapy-dose delivery and reduce the risk of febrile neutropenia in patients receiving adjuvant therapy: a validation study

BACKGROUND: The nadir value of the absolute neutrophil count (ANC) in the first cycle of chemotherapy is an effective predictor of subsequent neutropenic events. This study was designed to validate an earlier published study based on a retrospective data analysis from a prospective randomized clinical trial. METHODS: The original published model was applied to a trial of 143 patients to cross-validate the model. We also tested the specification of the model on our data by using a logistic regression model with several variables, including first-cycle nadir ANC, age, menopausal status, hormone-receptor status, previous radiotherapy, and first-cycle decrease in hemoglobin concentration. Patients received fluorouracil, doxorubicin, and cyclophosphamide every 21 or 28 days for six cycles without hematopoietic support from colony-stimulating factor. RESULTS: In the cross-validation analysis, the original model successfully classified patients by risk of neutropenic events (C = 0.78). When the model specification was tested, first-cycle nadir ANC was the sole significant (P < 0.0001) predictor of neutropenic events and the model had a good predictive power (C = 0.78). The estimated relative risk of 4.8 did not differ from the risk cited in the original model (P = 0.91). A significantly higher percentage of our patients with a low first-cycle nadir ANC of 0.25 × 10(9)/liter or less experienced febrile neutropenia (30% versus 10%, P = 0.04) and received at least 85% of the planned dose intensity (55% versus 32%, P = 0.05). CONCLUSIONS: The original risk model used to predict neutropenic events was validated by our study. This information can be used to target high-risk patients for prophylactic treatment with filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) in chemotherapy cycles 2 to 6

Economic analysis of a randomized clinical trial to compare filgrastim-mobilized peripheral-blood progenitor-cell transplantation and autologous bone marrow transplantation in patients with Hodgkin's and non-Hodgkin's lymphoma

Purpose: High-dose chemotherapy (HDC) with peripheral-blood progenitor cell (PBPC) and autologous bone marrow (ABM) transplant (T) has documented survival benefits for relapsed Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL). Treatment costs associated with HDC and its supportive care have restricted its use both on and off clinical trial. In a prospective randomized clinical trial, filgrastim-mobilized PBPCT resulted in faster recovery of bone marrow function, with less hospitalization and supportive care than ABMT. This study was undertaken to analyze the costs of the two strategies using prospectively collected data from a randomized clinical trial that compared filgrastim-mobilized PBPCT versus ABMT. Patients and Methods: Clinical results and resource utilization from a randomized clinical trial that compared filgrastim-mobilized PBPCT versus ABMT following carmustine, etoposide, cytarabine, and melphalan (BEAM) HDC for HD and NHL are presented. The trial was performed in six centers in Germany, the United Kingdom, and Belgium. Resource utilization data were used to project costs and Massey Cancer Center (MCC) in the United States incurred the cost of treating the cohort. Costs were projected to the United Stares, because the economic implications to United States centers are significant, costs of care vary markedly among countries but resource utilization on this trial did not, and a randomized trial is unlikely to be performed in the United States. Results: Fifty-eight patients with relapsed HD or NHL underwent HDC with BEAM. The PBPCT and ABMT groups had similar short-term survival after BEAM. PBPCT patients had a shorter hospitalization (median, 17 v 23 days; P = .002), neutrophil recovery (11 v 14 days; P = .005), platelet recovery to greater than or equal to 20 x 10(9)/L (16 v 23 days; P=.02), and days of platelet transfusions (6 v 10; P < .001). Estimated costs were $8,531 for ABM harvest and$5,760 for PBPC collection, including filgrastim mobilization. The total estimated average cost was $59,314 for each ABMT patient versus$45,792 for each PBPCT patient. Cost savings of $13,521 (23%) were due to shorter hospitalizations with less supportive care. Conclusion: PBPCT is as safe and more effective than ABMT for HD and NHL in the short term. PBPCT represents a significant cost savings due to lower autograft collection costs, shorter hospital stays, and less supportive care. The savings exceed the costs for filgrastim mobilization and PBPC collection. Actual savings will vary depending on local practice patterns, charges, and costs. (C) 1997 by American Society of Clinical Oncology

Teaching architectural regeneration

The absence of an adequate understanding of historic buildings and their conservation within the core curriculum of architectural or interiors education has long been noted internationally (Erder 1983; Orbaşlı and Whitbourn 2002; Santana and Settles 2014). For many years the typical design studio project took on the prospect of an empty plot and the construction of a new building. In the UK, the Royal Institute of Architects’ Plan of Work (RIBA 2013) typically follows the process of a new build, and this focus is also reflected in the Part II and Part III professional practice components of teaching. Although a conservation guide to the Plan of Work now exists (Feilden 2018), the emphasis remains on the conservation of listed buildings and monuments. There has, however, been a steady growth in Architecture Schools of students being set projects that consider existing buildings as a starting point.1 Some of these are short design assignments, others are linked into longer masters level programmes that combine design studio skills with teaching in the subject area. There are likely to be a range of reasons for a growing interest in reusing and repurposing existing buildings. Amongst them is a growing breadth of what is now valued as ‘heritage’, an increasing awareness in sustainability, a proliferation of high profile and award-winning projects that involve existing buildings and a demand from students who recognise that they are more than likely to encounter work in existing buildings in their careers as practicing architects. Oxford Brookes University’s School of Architecture has been a pioneer in this respect, teaching re-use and adaptation of existing buildings to Part II architecture students as a specialisation since the 1980s under the title Built Resource Management and later Built Resource Studies. At the time, teaching the conservation of what was considered the ‘ordinary end’ of the built environment was something new. Many early student projects focused on the regeneration of former industrial buildings, at a time when authorities across Europe were beginning to recognise the value of their industrial legacy and seek solutions to afford them a viable future. Built Resource Studies, in combination with a parallel programme in International Vernacular Architecture Studies, formed the foundations of the International Architectural Regeneration and Development programme (hereafter referred to as Architectural Regeneration). Established in 2006, the programme builds on an understanding in the fields of anthropology of architecture, area-based conservation, development studies and cultural sustainability. The masters programme has been attracting graduates with degrees in architecture, planning, interior design, law, arts, cultural heritage management as well as craftsmen. It also continues to be offered as a design specialism for Part II architecture students. As the programme has evolved to become more theoretically grounded and internationally expansive, the challenges of teaching design through the existing built environment remain as relevant as ever. Over time, the influence of the programme is evident in a growing focus on existing buildings as a subject matter in design studios across all levels of the school. As already discussed in this volume, architectural regeneration is more than simply considering the mechanics of adaptive re-use. In Chapter 10, Bassindale emphasises the need not only to understand the building, but also the set of values that characterise it. This process has to incorporate an understanding of ‘how the traditional buildings and morphology make up the character of the place, how they have come to be used, and how they relate to current economic, social, cultural and environmental needs’ (Orbaşlı and Vellinga 2008: 162). Whilst most programmes in the field of regeneration are focused on policy and planning issues, those centred around building conservation tend to be concerned with the preservation and restoration of monuments, historic buildings and places, with either a material conservation, or a heritage management focus. The revitalisation of historic quarters and traditional settlements with their vernacular traditions often requires an approach that simultaneously recognises conservation principles, but also delivers on the regeneration objectives of economic, social and cultural sustainability (Orbaşlı and Vellinga 2008). The purpose of this chapter is to reflect on our combined experiences of teaching architectural regeneration over the past thirty years. In doing so, we will discuss how within a time-bound programme we strive to achieve a balance between the practical, theoretical and research-based aspects of architectural regeneration. We particularly consider how an appreciation of the existing built environment in all its forms can be actively integrated into the architecture curriculum; how design teaching (and learning) can incorporate an understanding and appreciation of the theories that underpin decisions and the broader and far reaching social, environmental and economic implications that design decisions can have. A number of student projects are presented as case studies throughout the chapter