Tumor immunization strategies for enhancing the graft versus tumor activity of allogeneic bone marrow transplantation

Allogeneic bone marrow transplantation (BMT) is known to induce a beneficial anti-tumor immune response called graft-versus-tumor (GVT) activity. However, GVT activity is closely associated with graft-versus-host disease (GVHD), a potentially fatal immune response against antigens on normal recipient tissues. The T-cell populations mediating these two processes are often overlapping, but studies have shown that some donor T-cells can be tumor-specific. Therefore, the goal of this study was to develop strategies for preferentially activating donor T-cells capable of mediating GVT activity but not GVHD. The three hypotheses tested were: (1) Pre-transplant immunization of BMT donors with a recipient-derived tumor cell vaccine will induce a relative increase in GVT activity as compared to GVHD. (2) Post-transplant tumor immunization of BMT recipients will enhance GVT activity without exacerbating GVHD. (3) Pre-transplant immunization of BMT donors against a tumor-specific antigen will enhance GVT activity without exacerbating GVHD. ^ To test the first two hypotheses, C3H.SW mice (MHC-matched donors) were immunized with a C57BL/6 (recipient)-derived tumor cell vaccine (leukemia or fibrosarcoma) prior to BMT, or recipients were immunized starting one month after BMT. Both donor and recipient immunization led to a significant increase in GVT activity (enhanced recipient survival and decreased tumor growth). However, donor immunization also increased fatal GVHD, which was at least partially due to activation of alloreactive T-cells recognizing the immunodominant minor histocompatibility antigen B6dom1. GVT immunity following recipient immunization was not associated with an exacerbation of GVHD or a response to B6dom1. ^ To test the third hypothesis, influenza nucleoprotein (NP) was used as a model tumor antigen. C3H.SW donors were immunized against NP prior to BMT, which led to a significant increase in GVT activity. Although recipients were not completely protected against growth of antigen loss variant tumors, there was no increase in GVHD. ^ In conclusion, (1) immunization of allogeneic BMT donors with a recipient-derived tumor cell vaccine substantially increases GVT activity but also exacerbates GVHD, (2) post-transplant tumor immunization of allogeneic BMT recipients significantly increases GVT activity and survival without exacerbating GVHD, and (3) immunization of allogeneic BMT donors against a tumor-specific antigen significantly enhances GVT activity without exacerbating GVHD. ^

Food availability in the home and dietary intake of the Harris County Department of Education Head Start population

Background. The prevalence of obesity and overweight children has been an ongoing health epidemic in the US for the last several decades. The problem has consistently worsened and has disproportionately been the most prevalent among low socioeconomic status (SES) populations. Food availability in the home has been suggested to be a potential factor related to overweight and obesity, as availability is likely associated with intake. Food availability of low SES preschool aged children has not been well examined. The purpose of this study was to explore the food environment of the Harris County Department of Education (HCDE) Head Start population, and describe reported frequency of intake of particular food groups. The effect of food availability on reported intake was also examined.^ Methods. This was a cross-sectional study of secondary data analysis. Data obtained from 17 HCDE Head Start Centers was analyzed using PASW 18 Statistical Software. Demographic analyses included population, age, gender, race, parent occupation, type of home, and language spoken in the home. Descriptive statistics included reported availability of foods in the home as well as frequency of intake.^ Regression analysis examined the relationship of availability of foods on intake. The food categories included were: dark leafy green and orange vegetables, other vegetables, fruits, soda, salty snacks, and sweet snacks. For both vegetable categories reported intake of fresh, frozen, and canned vegetables were included. For the fruit category, intake of fresh, frozen, canned, and dried fruits were reported.^ Results. Results showed that 90-95% of parents reported having vegetables and fruits available in the home. However, the only significant relationship between availability and intake was for fresh fruit and dried fruit. No associations were seen among the vegetable groups. Other vegetables (bell peppers, eggplant, tomatoes, onions, iceberg lettuce, asparagus) that were frozen, approached significance for availability on intake, however once adjusted for confounders the relationship was no longer present. Among soda, salty snacks, and sweet snacks the only significant relationship was seen for soda availability and intake. Salty snacks and sweet snacks presence in the home was not a predictor of increased frequency of intake.^ Conclusions. This research supported the hypothesis that availability of foods has an impact on intake for fresh fruits, dried fruits and soda. No associations were seen for vegetables, salty snacks and sweet snacks. Additionally, most of the parents reported having fruits and vegetables in the home, but reported intakes were not meeting the Dietary Guidelines for Americans recommendations. Strengths of the study included the large sample size taken from numerous HCDE Head Start Centers. Limitations included questionable reliability of participant’s responses, ability to generalize to other populations, and the use of secondary data rather than prospectively collected data.^

DISCHARGE PLANNING: A PROCESS MODEL

As the requirements for health care hospitalization have become more demanding, so has the discharge planning process become a more important part of the health services system. A thorough understanding of hospital discharge planning can, then, contribute to our understanding of the health services system. This study involved the development of a process model of discharge planning from hospitals. Model building involved the identification of factors used by discharge planners to develop aftercare plans, and the specification of the roles of these factors in the development of the discharge plan. The factors in the model were concatenated in 16 discrete decision sequences, each of which produced an aftercare plan.^ The sample for this study comprised 407 inpatients admitted to the M. D. Anderson Hospital and Tumor Institution at Houston, Texas, who were discharged to any site within Texas during a 15 day period. Allogeneic bone marrow donors were excluded from the sample. The factors considered in the development of discharge plans were recorded by discharge planners and were used to develop the model. Data analysis consisted of sorting the discharge plans using the plan development factors until for some combination and sequence of factors all patients were discharged to a single site. The arrangement of factors that led to that aftercare plan became a decision sequence in the model.^ The model constructs the same discharge plans as those developed by hospital staff for every patient in the study. Tests of the validity of the model should be extended to other patients at the MDAH, to other cancer hospitals, and to other inpatient services. Revisions of the model based on these tests should be of value in the management of discharge planning services and in the design and development of comprehensive community health services.^

Children with acute leukemia: A comparison of outcomes and cost-effectiveness from allogeneic blood stem cell and bone marrow transplantation

The relative merits of PBSCT versus BMT for children with standard and high risk hematologic malignancies remain unclear. In a retrospective single center study, we compared allogeneic peripheral blood stem cell transplantation (PBSCT) (n=30) with bone marrow transplantation (BMT) (n=110) in children with acute leukemia. We studied recipients of HLA matched sibling stem cells, and of stem cells from alternative donors (HLA mismatched and/or unrelated) and determined whether sourcing the stem cells from PB or marrow affected engraftment, incidence of acute and chronic GvHD, and disease-free survival at 1 year. Our results show a modest reduction in time to engraftment from PB stem cells and no greater risk of GvHD, but illustrate that the severity of the underlying disease is by far the greatest determinant of 1 year survival. Patients in the BMT group had a higher treatment success rate and lower costs than the recipients of the PBSCT within the standard but not the high risk disease group, where the treatment success rate and the cumulative costs were lower in the PBSCT group compared to the BMT group. Our current incremental cost-effectiveness ratio and analysis of uncertainty suggest that allogeneic transplantation of bone marrow grafts was a more cost-effective treatment option compared to peripheral blood stem cells in patients with standard risk childhood acute leukemia disease. For high risk disease our data are less prescriptive, since the differences were more limited and the range of costs much larger. Neither option demonstrated a clear advantage from a cost-effectiveness standpoint.^