Massive Supergravity and Deconstruction

We present a simple superfield Lagrangian for massive supergravity. It comprises the minimal supergravity Lagrangian with interactions as well as mass terms for the metric superfield and the chiral compensator. This is the natural generalization of the Fierz-Pauli Lagrangian for massive gravity which comprises mass terms for the metric and its trace. We show that the on-shell bosonic and fermionic fields are degenerate and have the appropriate spins: 2, 3/2, 3/2 and 1. We then study this interacting Lagrangian using goldstone superfields. We find that a chiral multiplet of goldstones gets a kinetic term through mixing, just as the scalar goldstone does in the non-supersymmetric case. This produces Planck scale (Mpl) interactions with matter and all the discontinuities and unitarity bounds associated with massive gravity. In particular, the scale of strong coupling is (Mpl m^4)^1/5, where m is the multiplet's mass. Next, we consider applications of massive supergravity to deconstruction. We estimate various quantum effects which generate non-local operators in theory space. As an example, we show that the single massive supergravity multiplet in a 2-site model can serve the function of an extra dimension in anomaly mediation.Comment: 24 pages, 2 figures, some color. Typos fixed and refs added in v

Survival and freedom from progression in autotransplant lymphoma patients is independent of stem cell source: Further follow-up from the original randomised study to assess engraftment

Peripheral blood progenitor cells (PBPCs) have become the stem cell source of choice in autologous transplantation. In a prospective randomised trial, we previously demonstrated that autologous transplantation using filgrastim-mobilised PBPCs resulted in faster haematopoietic recovery with shorter hospitalisation and reduced platelet transfusions compared to bone marrow transplant (BMT). This study is a follow-up analysis evaluating the long-term clinical outcome. Seventy-two patients with advanced Hodgkin's disease or high-grade lymphoma were randomised to receive either filgrastim-mobilised PBPCs (n = 37) or bone marrow (n = 35) after BEAM chemotherapy. Fourteen patients withdrew from the study before commencing high-dose chemotherapy. Fourteen of the 58 patients who received treatment with chemotherapy and transplant have died, 6 (19%) in the ABMT arm and 8 (30%) in the PBPC transplant (PBPCT) arm. Twenty-five patients (81%) in the ABMT arm and 17 (63%) in the PBPCT arm, who received treatment, were in complete remission at the date of last follow-up. Progression-free survival and overall survival (OS) were similar for both arms (OS 81% at 46 months for ABMT versus 63% for PBPC; p = 0.38). Further prospective studies with larger number of patients need to be done to assess which source of stem cells may translate into a long-term clinical benefit for the patient

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

Downregulation of the Wnt inhibitor CXXC5 predicts a better prognosis in acute myeloid leukemia

The gene CXXC5 on 5q31 is frequently deleted in acute myeloid leukemia (AML) with del(5q), suggesting that inactivation of CXXC5 might play a role in leukemogenesis. Here, we investigated the functional and prognostic implications of CXXC5 expression in AML.CXXC5 mRNA was downregulated in AML with MLL rearrangements, t(8;21) and GATA2 mutations. As a mechanism of CXXC5 inactivation, we found evidence for epigenetic silencing by promoter methylation. Patients with CXXC5 expression below the median level had a lower relapse rate (45% vs 59%; P 5 .007) and a better overall survival (OS, 46% vs 28%; P < .001) and event-free survival (EFS, 36% vs 21%; P < .001) at 5 years, independent of cytogenetic risk groups and known molecular risk factors. In gene-expression profiling, lower CXXC5 expression was associated with upregulation of cell-cycling genes and codownregulation of genes implicated in leukemogenesis (WT1, GATA2, MLL, DNMT3B, RUNX1). Functional analyses demonstrated CXXC5 to inhibit leukemic cell proliferation and Wnt signaling and to affect the p53-dependent DNA damage response. In conclusion, our data suggest a tumor suppressor function of CXXC5 in AML. Inactivation of CXXC5 is associated with different leukemic pathways and defines an AML subgroup with better outcome