Hematopoietic stem cell transplantation in Switzerland: a comprehensive quality control report on centre effect.

Interest groups advocate centre-specific outcome data as a useful tool for patients in choosing a hospital for their treatment and for decision-making by politicians and the insurance industry. Haematopoietic stem cell transplantation (HSCT) requires significant infrastructure and represents a cost-intensive procedure. It therefore qualifies as a prime target for such a policy. We made use of the comprehensive database of the Swiss Blood Stem Cells Transplant Group (SBST) to evaluate potential use of mortality rates. Nine institutions reported a total of 4717 HSCT - 1427 allogeneic (30.3%), 3290 autologous (69.7%) - in 3808 patients between the years 1997 and 2008. Data were analysed for survival- and transplantation-related mortality (TRM) at day 100 and at 5 years. The data showed marked and significant differences between centres in unadjusted analyses. These differences were absent or marginal when the results were adjusted for disease, year of transplant and the EBMT risk score (a score incorporating patient age, disease stage, time interval between diagnosis and transplantation, and, for allogeneic transplants, donor type and donor-recipient gender combination) in a multivariable analysis. These data indicate comparable quality among centres in Switzerland. They show that comparison of crude centre-specific outcome data without adjustment for the patient mix may be misleading. Mandatory data collection and systematic review of all cases within a comprehensive quality management system might, in contrast, serve as a model to ascertain the quality of other cost-intensive therapies in Switzerland.

Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures. We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job-exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene-environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349. Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p = 0.009), in particular to latex (p = 0.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53-0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma. Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01.

Isolated limb perfusion with tumor necrosis factor and melphalan for non-resectable soft tissue sarcomas: long-term results on efficacy and limb salvage in a selected group of patients

Background And Objectives: Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a limb salvage therapy for non-resectable soft tissue sarcomas (STS) of the extremities. It is indicated for patients for whom amputation or debilitating surgery is the only alternative. It can be used either as an exclusive therapy (in palliation) or as a neo-adjuvant treatment, followed by marginal resection of tumor remnants with minimal functional impairment. Methods: Between February 1992 and March 2006, 57 TM-ILPs were performed on 51 patients with 88% high grade and 84% advanced stage tumors. Results: Mean follow-up is 38.9 months (4-159, median 22 months). Twenty-one percent patients had significant early complications, with 3 major re-operations, and 23% suffered long-lasting complications. Complete response was observed in 25%, partial response in 42%, stable disease in 14% and progressive disease in 14%. Resection of the tumor remnants was possible in 65%. A complementary treatment was necessary in 31%, mostly radiation therapy. A local recurrence was observed in 35%, after a mean of 20.3 months (2-78), and distant relapse was seen in 45%, after a mean of 13.4 months (5-196). Mean Disease-free survival was 14.9 months, and overall 5-year-survival 43.5%. Amputation rate at 5 years was 24%. Conclusions: TM-ILP is a conservative treatment with a high complications rate, but it can be successful even for the most severe STS of extremities. As a consequence the limb can be spared from amputation or debilitating surgery on the long term in about 75% of patients

Combined effects of interleukin-3 and interleukin-11 on hematopoiesis in irradiated mice

The survival rate and recovery of peripheral blood cells and platelets were studied in Balb/c mice subjected to different single doses of whole-body irradiation and treated with a combination of interleukin-3 (IL-3) and interleukin-11 (IL-11). In a first group of 20 mice, 7.5 Gy irradiation, immediately followed by 2 and 5 days therapy of IL-3 and IL-11, respectively, increased the survival rate to 82% compared to 20% in untreated controls. In a second group of mice irradiated with 7 Gy, we observed significantly higher platelet, white blood cell (WBC), and red blood cell (RBC) counts after treatment with both cytokines, as compared to IL-3 or IL-11 alone or untreated controls. In addition, the survival rate of the mice with the combined therapy was also increased to 84%, compared to 48% in untreated controls. Irradiation (8.5 Gy) gave 100% mortality for the control mice, and therapy with combined IL-3 plus IL-11 had only a marginal effect. Interestingly, syngeneic bone marrow transplantation (BMT) alone, performed 16 hours after irradiation, increased the survival rate to 70%, while BMT combined with administration of IL-3 plus IL-11 increased it to 97%. Furthermore, BMT combined with cytokine administration could partially prevent the severe WBC and RBC depletion observed in mice treated with BMT alone and promoted a more rapid recovery of platelets and RBC. These data show that the combination of IL-3 and IL-11 has a radioprotective effect and can enhance recovery of platelets, WBC, and RBC in irradiated mice. Combined IL-3 plus IL-11 therapy may be clinically useful in myelodepression, especially in platelet depletion related to radiation therapy or chemotherapy, or after bone marrow transplantation.