HapMap SNP Scanner: an online program to mine SNPs responsible for cell phenotype.

Minor histocompatibility (H) antigens are targets of graft-vs-host disease and graft-vs-tumor responses after human leukocyte antigen matched allogeneic hematopoietic stem cell transplantation. Recently, we reported a strategy for genetic mapping of linkage disequilibrium blocks that encoded novel minor H antigens using the large dataset from the International HapMap Project combined with conventional immunologic assays to assess recognition of HapMap B-lymphoid cell line by minor H antigen-specific T cells. In this study, we have constructed and provide an online interactive program and demonstrate its utility for searching for single-nucleotide polymorphisms (SNPs) responsible for minor H antigen generation. The website is available as 'HapMap SNP Scanner', and can incorporate T-cell recognition and other data with genotyping datasets from CEU, JPT, CHB, and YRI to provide a list of candidate SNPs that correlate with observed phenotypes. This method should substantially facilitate discovery of novel SNPs responsible for minor H antigens and be applicable for assaying of other specific cell phenotypes (e.g. drug sensitivity) to identify individuals who may benefit from SNP-based customized therapies.

Cidofovir for adenovirus infections after allogeneic hematopoietic stem cell transplantation: a survey by the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

Adenovirus is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation and there is no established therapy. Cidofovir has in vitro efficacy against adenovirus. We performed a retrospective analysis of 45 patients treated with cidofovir for adenovirus from 10 centers. In total, 16 patients had definite adenovirus disease, 13 probable disease, and 16 asymptomatic infections. A total of 31 (69%) patients were successfully treated with cidofovir, 10 failed, and four were not evaluable owing to early death from other causes. Cidofovir therapy was successful in 10 patients with adenovirus disease, 10 patients with probable disease, and in 10 patients with asymptomatic infections. The overall survival at 28 days and 6 months after initiation of cidofovir therapy was 76 and 46%, respectively. Of the patients, 18 developed toxicity associated with cidofovir: 14 developed renal toxicity and four other types of toxicities. We conclude that cidofovir may be useful against adenovirus after allogeneic hematopoietic stem cell transplantation but additional studies are needed.

Allogeneic bone marrow transplantation for childhood relapsed acute lymphoblastic leukemia: comparison of outcome in patients with and without a matched family donor.

We evaluated the role of BMT in a cohort of 56 children with ALL relapsing after uniform initial treatment protocols in a single institution between 1990 and 1997. The patients were commenced on a single intensive chemotherapy regimen. All patients with a matched family donor (MFD) were recommended to receive BMT. The outcome was significantly better for patients with a MFD. The overall survival at 8 years was 60.0% (95% CI 35.7-77.6%) and 13.5% (95% CI 4.0-28.6%) for patients with and without MFDs (log-rank chi = 7.50 P = 0.0062). The event-free survival at 8 years was 55.0% (95% CI 11.1-31.3%) and 9.2% (95% CI 2.0-23.3%) for patients with and without MFDs (log-rank chi = 8.87 P = 0.0029). Multivariate analysis confirmed the survival advantage of BMT. There was no statistically significant difference in survival for patients initially relapsing within 3 years of first remission compared to children relapsing beyond 3 years. BMT provides a clear survival advantage for children following their first relapse of ALL. We recommend BMT for all children following first relapse of ALL if a MFD is available.

Bone marrow transplantation for paediatric AML in first remission: a systematic review and meta-analysis.

For children with AML in CR1, the major consolidation therapies are BMT, ABMT and intensive chemotherapy. The relative effectiveness of these strategies is still debated. We conducted a systematic review and meta-analysis of trials to determine the effectiveness of BMT and ABMT in CR1 in paediatric AML. Eligible studies enrolled patients <21 years from 1985 to 2000 with AML in CR1. Two groups of studies were identified: (1) Those comparing the outcome of patients with and without a histocompatible family donor; and (2) Randomised controlled trials (RCT) comparing ABMT with non-myeloablative chemotherapy. The relative risk statistic was calculated for outcomes of interest in each trial. If there was no excessive heterogeneity between trials the results were pooled, and an overall relative risk and risk difference for treatment effect across trials were calculated. Results of the analysis showed that allocation to BMT reduced risk of relapse and improved disease-free and overall survival. For ABMT, heterogeneity of effect between RCTs prevented pooling of results. In conclusion, BMT from a histocompatible family donor improves patient outcome. Data are insufficient to determine whether this is true for all subgroups of AML, and whether ABMT is superior to non-myeloablative chemotherapy. An individual patient data meta-analysis is required to further evaluate the available data.

Searching for a cord blood unit for transplantation based on the unit's cell count.

Although recipients of unrelated cord blood can tolerate a greater degree of HLA-disparity than recipients of unrelated bone marrow, cell dose is also important. After an unsuccessful search for a bone marrow donor, and after initially dismissing a cord blood search because the patient was 52 kg, we used a different search strategy to identify an unrelated cord blood unit. This led to successful engraftment and transplantation for a patient with no bone marrow donor.

Competencies required of health service managers in the 1990s.

A mailed survey of three hundred and twenty Australian health service managers provided a ranked list of competencies perceived as essential for effective management. A high level of concordance was evident as to the relative importance of forty-nine competencies generated in four focus groups. Of seven clusters of competencies: leadership, decision-making and public relations/communication were ranked most highly. Only eight differences between the various groups of managers reached significance and these related to level of manager, years of management experience, discipline and size and type of organisation. This study extends understanding of the 'real world' management development needs of one group of the health industry. In conclusion, it is suggested that educators and managers need to cooperate more closely to develop learning programs which facilitate the acquisition, practice and assessment of identified competencies.

Changing with the times: reconfiguring a mental health facility in response to changing market conditions.

A 130-bed private mental health hospital in Ann Arbor, Michigan, was a state-of-the-art, progressive facility when it was built in 1986. Since then, changing reimbursement patterns and the shift from inpatient to outpatient services have led to an organizational and physical reconfiguration of the facility to accommodate both mental health and chemical dependency programs. This paper describes the original design of the building and how it was modified in 1990 to achieve organizational objectives and enhance patient care.